Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of fi...Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of first-line anti-TB drugs(ATDs)-particularly isoniazid,rifampicin,and pyrazinamide-poses a considerable risk,as these agents are associated with a significant incidence of ATD-induced liver injury(AT-DILI).The clinical presentation of AT-DILI can range from asymptomatic elevations in serum transaminases,which may resolve spontaneously due to hepatic adaptation,to acute liver failure(ALF),a potentially life-threatening condition.A recent meta-analysis reported a global incidence of AT-DILI of 11.5%,with rates varying from 2%to 28%.Approximately 7%of patients with AT-DILI progress to ALF,a condition characterized by a poor survival rate with medical therapy.ATD-induced ALF(AT-ALF)is clinically indistinguishable from ALF due to other causes and disproportionately affects young female patients,typically within eight weeks of treatment initiation.Emergency liver transplantation has become an effective therapeutic option for AT-ALF,although outcomes are generally poorer compared to elective transplantation.This minireview provides a comprehensive overview of AT-ALF,covering its epidemiology,risk factors,clinical presentation,prognosis,and treatment options.展开更多
AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
AIM: To evaluate the eff icacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospect...AIM: To evaluate the eff icacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospectively analyzed the colonoscopic fi ndings before and after short term anti- tuberculosis treatment in 18 patients with nonspecifi c ulcers on the ileocecal area and compared them with 7 patients of confi rmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS: Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short- term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the "suspicious tuberculous colitis group" showing healing of ulcers and erosions and another is the "suspicious inflammatory bowel disease group" showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the "suspicious tuberculous colitis group" were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the "suspicious inflammatorybowel disease group" were f inally diagnosed as Crohn's disease or nonspecifi c colonic ulcers during long-term follow up. CONCLUSION: Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecif ic ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis.展开更多
Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and r...Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.展开更多
AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments o...AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of antituberculosis.METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded.RESULTS: The rate of hepatotoxicity occurred in 26 (59%)TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P<0.01).CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.展开更多
Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was ...Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.展开更多
Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxy...Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.展开更多
The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoni...The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of <i>Tetrapleura tetraptera</i> against <i>Mycobacterium tuberculosis</i> and MDR-TB and the phytochemical present. The leaves of <i>Tetrapleura tetraptera </i>were collected, weighed, dried and pulverized to powder. The pulverized leaves of <i>Tetrapleura tetraptera </i>were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques.<i> M. tuberculosis</i> and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible <i>M. tuberculosis</i> and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that <i>Tetrapleura tetraptera crude </i>had activities against <i>M. tuberculosis</i> at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of <i>M. tuberculosis </i>at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. <i>T. tetraptra </i>possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.展开更多
Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases an...Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.展开更多
Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings ha...Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies;it would have large positive repercussions for developing countries.展开更多
Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasi...Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.展开更多
Background: TB (Tuberculosis) is the second leading killer infectious disease after HIV (human immunodeficiency virus). Its incidence is worsened by development of multi-drag resistant and extensive drug resistan...Background: TB (Tuberculosis) is the second leading killer infectious disease after HIV (human immunodeficiency virus). Its incidence is worsened by development of multi-drag resistant and extensive drug resistant TB stxains. Available treatment regimens are expensive, toxic and lengtjy resulting to problems of non-adherence and inadequate response. Medicinal plants on the other hand may offer hope for developing alternative medicine for treatment of TB. This study evaluated the anti-tuberculosis activity of Echinops amplexicaulis. Materials and methods: Total crude extracts ofE. amplexicaulis were tested for activity against a wild strain resistant to Rifampicin and Isoniazid (MDR), a fully susceptible laboratory strain (H37Rv) and Mycobacwrium boris (BCG strain) using disk diffusion method. MIC (minimum inhibitory concentration) was determined using Middlebrook 7H9 broil1. The strains were sub-cultured on Middlebrook 7H10 medium and MBC (minimum bactericidal concentration) determined. Susceptibility was evaluated by measuring zones of inhibition; MIC was obtained as the lowest concentration with no significant growth as shown by clog formation ofMTB (Mycobacwria tuberculosis) cells on the walls of the macro broth tube and MBC was obtained as the lowest concentration that inhibited growth of MTB colonies on Middlebrook 7H10 medium. Results: The extract showed a significant effect at a concentration of 50 mg/mL against all the three test strains F (2, 18) = 437.7, p = 0.00. It exhibited a MIC of 0.0488 mg/mL against MDR-TB and M. boris. Its MBC was the same at 0.0977 mg/mL against both MDR TB and M. boris. The MIC was much lower (0.0122 mg/mL) for the H37Rv strain. Terpenoids, alkaloids and tannins were present in large amount in the extract while saponins were present in small amounts. Flavonoids were not detected in the extract. Conclusion: E. amplexicaulis has the potential to be developed into new anti-TB drug and outcome of tile study supports the folkloric claims of anti-tuberculosis activity of tile plant.展开更多
The efficacy of levofloxacin combined with traditional anti-tuberculosis drugs was compared between the two groups. Methods: The trial was conducted between January 2021 and March 2022 and included a total of 78 patie...The efficacy of levofloxacin combined with traditional anti-tuberculosis drugs was compared between the two groups. Methods: The trial was conducted between January 2021 and March 2022 and included a total of 78 patients. In this trial, 39 patients received conventional anti-tuberculosis therapy;Results: Forty patients received conventional antituberculous drugs combined with levofloxacin. The efficacy of the two methods was compared, including safety and efficacy. Results: The efficacy of the two groups were statistically significant (P<0.05), significantly higher than that of the control group. In terms of safety, there was no difference in side effects or overall morbidity between the two groups (P>0.05). The content of inflammatory factors in the experimental group was significantly lower than that in the control group, while the immune function index was significantly higher than that in the control group (P<0.05). Conclusion: Levofloxacin combined with conventional anti-tuberculosis regimen in the treatment of pulmonary tuberculosis patients can not only enhance the efficacy, but also have high safety, which is worthy of active application during the clinical treatment.展开更多
Tuberculosis(TB)belongs to infectious diseases leading to the high mortality and morbidity worldwide.Since long-term bacilli burden leads to metabolic disorders in TB patients,metabolic biomarkers with diagnosis and p...Tuberculosis(TB)belongs to infectious diseases leading to the high mortality and morbidity worldwide.Since long-term bacilli burden leads to metabolic disorders in TB patients,metabolic biomarkers with diagnosis and prognosis potential are worthy of elucidation.In this study,^(1)H nuclear magnetic resonance spectroscopy(^(1)H NMR)-based plasma metabolomics were investigated dynamically in onset TB patients undergoing conventional anti-TB chemotherapy before and along with the treatment.We found that metabolomic profiles altered before and after the treatment of 2 and 4 months,among which four amino acids,including 4-aminobenzoate,phenylalanine,serine,and threonine,were screened out with significant decrease at 6 months after anti-TB therapy in the training longitudinal samples and validated in another longitudinal samples.Moreover,we have also confirmed the increase of 4 amino acid contents in the periphery of active TB patients when compared to those in healthy controls(HCs).Receiver operating characteristic(ROC)analysis revealed that the combination of 4 amino acids was able to distinguish TB patients from HC with an area under the curve(AUC)value of 0.9120.031(P<0.0001).Therefore,our study has identified an amino acid panel with increased levels in active TB patients and declined along with conventional anti-TB treatment,which might be potential in distinguishing TB patients from HCs as well as prognosis candidates in clinics.展开更多
Objective:To observe the clinical efficacy of acupuncture at the front-Mu points and the lower He-sea points combined with Western medication in the treatment of diarrhea induced by anti-tuberculosis drugs,as well as ...Objective:To observe the clinical efficacy of acupuncture at the front-Mu points and the lower He-sea points combined with Western medication in the treatment of diarrhea induced by anti-tuberculosis drugs,as well as the effects on clinical symptoms and serum albumin.Methods:Seventy patients with diarrhea caused by anti-tuberculosis drugs were divided into an observation group and a control group according to the different treatment methods,with 35 cases in each group.Both groups were treated with the same Western medication,and the observation group was additionally treated with acupuncture at the front-Mu points and the lower He-sea points.After treatment,changes in the Hart score,traditional Chinese medicine(TCM)symptom score,and serum albumin were observed in both groups.Results:There was no statistically significant difference in the Hart score,TCM symptom score,and serum albumin level between the two groups before treatment(P>0.05).No adverse reactions occurred during treatment in either group.After 3 d of treatment,the total effective rate of the observation group was 68.6%,which was higher than 25.7%of the control group(P<0.01);after 7 d of treatment,the total effective rate of both the observation group and the control group was 100.0%,but the cured rate of the observation group was 80.0%,which was significantly higher than 2.9%of the control group(P<0.01).The Hart score and TCM symptom score of both groups after 3 d and 7 d of treatment were significantly lower than those before treatment(P<0.05),and the scores of the observation group were lower than those of the control group(P<0.05).After 7 d of treatment,the albumin level of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The addition of acupuncture at the front-Mu points combined with lower He-sea points to routine Western mediation treatment for diarrhea induced by anti-tuberculosis drugs is more effective than Western medication alone and can improve the clinical symptoms and nutritional status of the patients at an early stage.展开更多
Objective:To investigate the evolution of herbal medicine in treating tuberculosis(TB)and encourage anti-TB drug discovery and development.Methods:In this study,477 ancient traditional Chinese medicine formulae were c...Objective:To investigate the evolution of herbal medicine in treating tuberculosis(TB)and encourage anti-TB drug discovery and development.Methods:In this study,477 ancient traditional Chinese medicine formulae were collected from the Dictionary of Traditional Chinese Medicine Prescriptions and 172 modern Chinese medicine formulae(from 1986 to 2016)were collected by searching 4 databases:Wan Fang Data Knowledge Service Platform,China National Knowledge Infrastructure Database(CNKI),China Science and Technology Journal Database(VIP)and Chinese Bio-medical Literature and Retrieval System(Sino Med)in Chinese.We restricted the search to publications in Chinese.Further data analysis was done using the Traditional Chinese Medicine Inheritance Support System version 2 Software.Results:There were 425 herbs in the 477 ancient formulae and 257 herbs in the 172 modern formulae.Half of the top 30 herbs were shared by both modern and ancient prescriptions.They are Radix Ophiopogonis,Astragalus membranaceus,Fritillaria cirrhosa,Dried rehmannia glutinosa,Poria cocos,Angelica sinensis,Prepared rehmannia glutinosa,Platycodon Root,Radix paeoniae alba,Schisandra chinensis,Bighead atractylodes rhizome,Rhizoma anemarrhenae,Cortex lycii radicis and Radix Scutellariae.Only two groups of herbs with a high correlation coefficient were found in both modern and ancient prescriptions,the Dried rehmannia glutinosa with Radix ophiopogonis,and Radix ophiopogonis with Prepared rehmannia glutinosa.There were 9 and 15 core herb combinations in modern and ancient prescriptions,respectively,but no one was found simutaniously in both modern and ancient prescriptions.Conclusions:Although there were wide variations in the herb groups and herb combinations in the formulae,half of the top 30 herbs were found in both modern and ancient prescriptions.The core herb combinations in modern and ancient prescriptions could help us to improve the priscription for treatment of TB.展开更多
Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until sympto...Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.展开更多
Objective:To study the chemical constituents and the anti-tuberculosis activity of methanol and chloroform ink extracts of Sepiella inermis.Methods:Pulverized ink powder was extracted separately with chloroform and me...Objective:To study the chemical constituents and the anti-tuberculosis activity of methanol and chloroform ink extracts of Sepiella inermis.Methods:Pulverized ink powder was extracted separately with chloroform and methanol.Chemical analysis was carried out by UV-VIS spectrophotometer,FT-IR and GC-MS.Crude extracts were tested in vitro for their activity against Mycobacterium tuberculosis using Lowenstein Jensen(L-J)medium.Activity in L-J medium was assessed by mean reduction in number of colonies on extract containing bottles as compared to extract free controls.Results:GC-MS of methanol extract revealed four compounds viz.hexadecanoic acid,9,12-octadecadienoic acid,9-octadecenoic acid and octadecanoic acid.The chloroform extract containing fourteen compounds.The methanol extract exhibited anti-tuberculosis activity in L-J medium at 64μg/mL with the observed inhibition of 14 CFU.Chloroform extract displayed a weak activity against Mycobacterium tuberculosis.Conclusions:This investigation showed the methanol extract exhibited significant activity against Mycobacterium tuberculosis than chloroform extract.Since ink of sepia is available abundantly as a waste material,further studies aimed at isolation and efficacy of active substances pave the way for new anti-tuberculosis drugs.展开更多
Objective:To identify factors associated with hepatotoxicity during the intensive phase of treatment in tuberculosis(TB)patients.Methods:A case-control study was conducted of TB patients treated with first-line anti-T...Objective:To identify factors associated with hepatotoxicity during the intensive phase of treatment in tuberculosis(TB)patients.Methods:A case-control study was conducted of TB patients treated with first-line anti-TB drugs from 2013 to 2020.Cases were defined as patients who developed hepatotoxicity,while controls were those without hepatotoxicity,at a 1:2 ratio.Controls were randomly selected from the same hospitals as the cases.The primary outcome was the occurrence of hepatotoxicity during the intensive treatment phase,with data retrospectively collected from medical records.Descriptive statistics and multiple logistic regression with backward elimination were used for analysis.Results:Among 3021 tuberculosis patients who received first-line anti-tuberculosis regimen,50 had abnormal liver function and 14 developed hepatotoxictiy.In addition,2957 patients had normal liver function and 128 served as controls for this analysis.Multiple logistic regression analysis revealed that female patients had about twice the risk of hepatotoxicity compared to males(adjusted OR 2.25,95%CI 1.11-4.59),and patients with HIV coinfection were nearly 10 times more likely to develop hepatotoxicity than those without HIV(adjusted OR 9.74,95%CI 3.12-30.41).Conclusions:Female sex and HIV coinfection were found to be significant risk factors for hepatotoxicity during the intensive phase of TB treatment.Enhanced monitoring and preventive strategies are recommended for these high-risk groups to reduce the risk of hepatotoxicity.展开更多
Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass...Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.展开更多
文摘Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of first-line anti-TB drugs(ATDs)-particularly isoniazid,rifampicin,and pyrazinamide-poses a considerable risk,as these agents are associated with a significant incidence of ATD-induced liver injury(AT-DILI).The clinical presentation of AT-DILI can range from asymptomatic elevations in serum transaminases,which may resolve spontaneously due to hepatic adaptation,to acute liver failure(ALF),a potentially life-threatening condition.A recent meta-analysis reported a global incidence of AT-DILI of 11.5%,with rates varying from 2%to 28%.Approximately 7%of patients with AT-DILI progress to ALF,a condition characterized by a poor survival rate with medical therapy.ATD-induced ALF(AT-ALF)is clinically indistinguishable from ALF due to other causes and disproportionately affects young female patients,typically within eight weeks of treatment initiation.Emergency liver transplantation has become an effective therapeutic option for AT-ALF,although outcomes are generally poorer compared to elective transplantation.This minireview provides a comprehensive overview of AT-ALF,covering its epidemiology,risk factors,clinical presentation,prognosis,and treatment options.
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
文摘AIM: To evaluate the eff icacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospectively analyzed the colonoscopic fi ndings before and after short term anti- tuberculosis treatment in 18 patients with nonspecifi c ulcers on the ileocecal area and compared them with 7 patients of confi rmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS: Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short- term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the "suspicious tuberculous colitis group" showing healing of ulcers and erosions and another is the "suspicious inflammatory bowel disease group" showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the "suspicious tuberculous colitis group" were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the "suspicious inflammatorybowel disease group" were f inally diagnosed as Crohn's disease or nonspecifi c colonic ulcers during long-term follow up. CONCLUSION: Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecif ic ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis.
基金supported by Surface Project of Shandong Provincial Natural Science Foundation(No.ZR2014HM081)
文摘Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.
文摘AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of antituberculosis.METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded.RESULTS: The rate of hepatotoxicity occurred in 26 (59%)TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P<0.01).CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.
文摘Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.
基金financially supported by the National Natural Science Foundation of China (Nos. 82030107 and 21702046)the China Postdoctoral Science Foundation (No. 2018M632757)+1 种基金the Key Scientific and Technological Project of Henan Province (Nos.212102311064 and 212102310870)the Innovation Scientists and Technicians Troop Construction Projects of Henan Province(No. 20IRTSTHN020)。
文摘Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.
文摘The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of <i>Tetrapleura tetraptera</i> against <i>Mycobacterium tuberculosis</i> and MDR-TB and the phytochemical present. The leaves of <i>Tetrapleura tetraptera </i>were collected, weighed, dried and pulverized to powder. The pulverized leaves of <i>Tetrapleura tetraptera </i>were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques.<i> M. tuberculosis</i> and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible <i>M. tuberculosis</i> and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that <i>Tetrapleura tetraptera crude </i>had activities against <i>M. tuberculosis</i> at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of <i>M. tuberculosis </i>at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. <i>T. tetraptra </i>possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.
文摘Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.
文摘Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies;it would have large positive repercussions for developing countries.
文摘Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.
文摘Background: TB (Tuberculosis) is the second leading killer infectious disease after HIV (human immunodeficiency virus). Its incidence is worsened by development of multi-drag resistant and extensive drug resistant TB stxains. Available treatment regimens are expensive, toxic and lengtjy resulting to problems of non-adherence and inadequate response. Medicinal plants on the other hand may offer hope for developing alternative medicine for treatment of TB. This study evaluated the anti-tuberculosis activity of Echinops amplexicaulis. Materials and methods: Total crude extracts ofE. amplexicaulis were tested for activity against a wild strain resistant to Rifampicin and Isoniazid (MDR), a fully susceptible laboratory strain (H37Rv) and Mycobacwrium boris (BCG strain) using disk diffusion method. MIC (minimum inhibitory concentration) was determined using Middlebrook 7H9 broil1. The strains were sub-cultured on Middlebrook 7H10 medium and MBC (minimum bactericidal concentration) determined. Susceptibility was evaluated by measuring zones of inhibition; MIC was obtained as the lowest concentration with no significant growth as shown by clog formation ofMTB (Mycobacwria tuberculosis) cells on the walls of the macro broth tube and MBC was obtained as the lowest concentration that inhibited growth of MTB colonies on Middlebrook 7H10 medium. Results: The extract showed a significant effect at a concentration of 50 mg/mL against all the three test strains F (2, 18) = 437.7, p = 0.00. It exhibited a MIC of 0.0488 mg/mL against MDR-TB and M. boris. Its MBC was the same at 0.0977 mg/mL against both MDR TB and M. boris. The MIC was much lower (0.0122 mg/mL) for the H37Rv strain. Terpenoids, alkaloids and tannins were present in large amount in the extract while saponins were present in small amounts. Flavonoids were not detected in the extract. Conclusion: E. amplexicaulis has the potential to be developed into new anti-TB drug and outcome of tile study supports the folkloric claims of anti-tuberculosis activity of tile plant.
文摘The efficacy of levofloxacin combined with traditional anti-tuberculosis drugs was compared between the two groups. Methods: The trial was conducted between January 2021 and March 2022 and included a total of 78 patients. In this trial, 39 patients received conventional anti-tuberculosis therapy;Results: Forty patients received conventional antituberculous drugs combined with levofloxacin. The efficacy of the two methods was compared, including safety and efficacy. Results: The efficacy of the two groups were statistically significant (P<0.05), significantly higher than that of the control group. In terms of safety, there was no difference in side effects or overall morbidity between the two groups (P>0.05). The content of inflammatory factors in the experimental group was significantly lower than that in the control group, while the immune function index was significantly higher than that in the control group (P<0.05). Conclusion: Levofloxacin combined with conventional anti-tuberculosis regimen in the treatment of pulmonary tuberculosis patients can not only enhance the efficacy, but also have high safety, which is worthy of active application during the clinical treatment.
基金supported by grants from the National Key Research and Development Program of China(No.2021YFC2301500)Chinese National Mega Science and Technology Program on Infectious Diseases(Nos.2018ZX10731301-001-004 and 2018ZX10302301-002-002)+4 种基金Shanghai 2020“Science and Technology Innovation Action Plan”Technological Innovation Fund of China(No.20Z11900500)Science Foundation of Shanghai Municipal Commission of Science and Technology,China(No.24ZR1442000)Postdoctoral Fellowship Program of CPSF of China(No.GZC20241041),National Natural Science Foundation of China(No.81501361)Innovative Research Team of High-level Local Universities in Shanghai,China(No.SSMU-ZLCX20180202)Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases,China。
文摘Tuberculosis(TB)belongs to infectious diseases leading to the high mortality and morbidity worldwide.Since long-term bacilli burden leads to metabolic disorders in TB patients,metabolic biomarkers with diagnosis and prognosis potential are worthy of elucidation.In this study,^(1)H nuclear magnetic resonance spectroscopy(^(1)H NMR)-based plasma metabolomics were investigated dynamically in onset TB patients undergoing conventional anti-TB chemotherapy before and along with the treatment.We found that metabolomic profiles altered before and after the treatment of 2 and 4 months,among which four amino acids,including 4-aminobenzoate,phenylalanine,serine,and threonine,were screened out with significant decrease at 6 months after anti-TB therapy in the training longitudinal samples and validated in another longitudinal samples.Moreover,we have also confirmed the increase of 4 amino acid contents in the periphery of active TB patients when compared to those in healthy controls(HCs).Receiver operating characteristic(ROC)analysis revealed that the combination of 4 amino acids was able to distinguish TB patients from HC with an area under the curve(AUC)value of 0.9120.031(P<0.0001).Therefore,our study has identified an amino acid panel with increased levels in active TB patients and declined along with conventional anti-TB treatment,which might be potential in distinguishing TB patients from HCs as well as prognosis candidates in clinics.
文摘Objective:To observe the clinical efficacy of acupuncture at the front-Mu points and the lower He-sea points combined with Western medication in the treatment of diarrhea induced by anti-tuberculosis drugs,as well as the effects on clinical symptoms and serum albumin.Methods:Seventy patients with diarrhea caused by anti-tuberculosis drugs were divided into an observation group and a control group according to the different treatment methods,with 35 cases in each group.Both groups were treated with the same Western medication,and the observation group was additionally treated with acupuncture at the front-Mu points and the lower He-sea points.After treatment,changes in the Hart score,traditional Chinese medicine(TCM)symptom score,and serum albumin were observed in both groups.Results:There was no statistically significant difference in the Hart score,TCM symptom score,and serum albumin level between the two groups before treatment(P>0.05).No adverse reactions occurred during treatment in either group.After 3 d of treatment,the total effective rate of the observation group was 68.6%,which was higher than 25.7%of the control group(P<0.01);after 7 d of treatment,the total effective rate of both the observation group and the control group was 100.0%,but the cured rate of the observation group was 80.0%,which was significantly higher than 2.9%of the control group(P<0.01).The Hart score and TCM symptom score of both groups after 3 d and 7 d of treatment were significantly lower than those before treatment(P<0.05),and the scores of the observation group were lower than those of the control group(P<0.05).After 7 d of treatment,the albumin level of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The addition of acupuncture at the front-Mu points combined with lower He-sea points to routine Western mediation treatment for diarrhea induced by anti-tuberculosis drugs is more effective than Western medication alone and can improve the clinical symptoms and nutritional status of the patients at an early stage.
基金Supported by National Natural Science Foundation of China(No.81871691)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding(No.XMLX201812)。
文摘Objective:To investigate the evolution of herbal medicine in treating tuberculosis(TB)and encourage anti-TB drug discovery and development.Methods:In this study,477 ancient traditional Chinese medicine formulae were collected from the Dictionary of Traditional Chinese Medicine Prescriptions and 172 modern Chinese medicine formulae(from 1986 to 2016)were collected by searching 4 databases:Wan Fang Data Knowledge Service Platform,China National Knowledge Infrastructure Database(CNKI),China Science and Technology Journal Database(VIP)and Chinese Bio-medical Literature and Retrieval System(Sino Med)in Chinese.We restricted the search to publications in Chinese.Further data analysis was done using the Traditional Chinese Medicine Inheritance Support System version 2 Software.Results:There were 425 herbs in the 477 ancient formulae and 257 herbs in the 172 modern formulae.Half of the top 30 herbs were shared by both modern and ancient prescriptions.They are Radix Ophiopogonis,Astragalus membranaceus,Fritillaria cirrhosa,Dried rehmannia glutinosa,Poria cocos,Angelica sinensis,Prepared rehmannia glutinosa,Platycodon Root,Radix paeoniae alba,Schisandra chinensis,Bighead atractylodes rhizome,Rhizoma anemarrhenae,Cortex lycii radicis and Radix Scutellariae.Only two groups of herbs with a high correlation coefficient were found in both modern and ancient prescriptions,the Dried rehmannia glutinosa with Radix ophiopogonis,and Radix ophiopogonis with Prepared rehmannia glutinosa.There were 9 and 15 core herb combinations in modern and ancient prescriptions,respectively,but no one was found simutaniously in both modern and ancient prescriptions.Conclusions:Although there were wide variations in the herb groups and herb combinations in the formulae,half of the top 30 herbs were found in both modern and ancient prescriptions.The core herb combinations in modern and ancient prescriptions could help us to improve the priscription for treatment of TB.
基金supported by the funds for the construction of key medical disciplines in Shenzhen.
文摘Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.
基金Funded by University Grants Commission,Govt.of India,New Delhi under the college with Potential for Excellence scheme(Grant No.F-12-1/2008/NS/PE dated15-10-2010).
文摘Objective:To study the chemical constituents and the anti-tuberculosis activity of methanol and chloroform ink extracts of Sepiella inermis.Methods:Pulverized ink powder was extracted separately with chloroform and methanol.Chemical analysis was carried out by UV-VIS spectrophotometer,FT-IR and GC-MS.Crude extracts were tested in vitro for their activity against Mycobacterium tuberculosis using Lowenstein Jensen(L-J)medium.Activity in L-J medium was assessed by mean reduction in number of colonies on extract containing bottles as compared to extract free controls.Results:GC-MS of methanol extract revealed four compounds viz.hexadecanoic acid,9,12-octadecadienoic acid,9-octadecenoic acid and octadecanoic acid.The chloroform extract containing fourteen compounds.The methanol extract exhibited anti-tuberculosis activity in L-J medium at 64μg/mL with the observed inhibition of 14 CFU.Chloroform extract displayed a weak activity against Mycobacterium tuberculosis.Conclusions:This investigation showed the methanol extract exhibited significant activity against Mycobacterium tuberculosis than chloroform extract.Since ink of sepia is available abundantly as a waste material,further studies aimed at isolation and efficacy of active substances pave the way for new anti-tuberculosis drugs.
文摘Objective:To identify factors associated with hepatotoxicity during the intensive phase of treatment in tuberculosis(TB)patients.Methods:A case-control study was conducted of TB patients treated with first-line anti-TB drugs from 2013 to 2020.Cases were defined as patients who developed hepatotoxicity,while controls were those without hepatotoxicity,at a 1:2 ratio.Controls were randomly selected from the same hospitals as the cases.The primary outcome was the occurrence of hepatotoxicity during the intensive treatment phase,with data retrospectively collected from medical records.Descriptive statistics and multiple logistic regression with backward elimination were used for analysis.Results:Among 3021 tuberculosis patients who received first-line anti-tuberculosis regimen,50 had abnormal liver function and 14 developed hepatotoxictiy.In addition,2957 patients had normal liver function and 128 served as controls for this analysis.Multiple logistic regression analysis revealed that female patients had about twice the risk of hepatotoxicity compared to males(adjusted OR 2.25,95%CI 1.11-4.59),and patients with HIV coinfection were nearly 10 times more likely to develop hepatotoxicity than those without HIV(adjusted OR 9.74,95%CI 3.12-30.41).Conclusions:Female sex and HIV coinfection were found to be significant risk factors for hepatotoxicity during the intensive phase of TB treatment.Enhanced monitoring and preventive strategies are recommended for these high-risk groups to reduce the risk of hepatotoxicity.
基金supported by the National Natural Science Foundation of China(No.32170403)the 111 Center from Ministry of Education of China and the State Administration of Foreign Experts Affairs of China(No.B18056)+1 种基金the“Double First-Class”University Project(No.CPU2018GF03)the Drug Innovation Major Project(Nos.2018ZX09711-001-007 and 2018ZX09735002-003)。
文摘Two novel fungal metabolites,asperochones A and B,were obtained from an Aspergillus sp.Their structures were determined by 1D/2D nuclear magnetic resonance(NMR)spectroscopy,high resolution electrospray ionization mass spectroscopy(HRESIMS),and single-crystal X-ray diffraction analysis.Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system,and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers.Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides.In addition,asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.