From 1975 to 1987, 112 patients with loco-regional recurrence of nasopharyngeal carcinoma (N P C) were treated again with radiation at our hospital. All cases were proven histologically by biopsy. Of these patients, 9...From 1975 to 1987, 112 patients with loco-regional recurrence of nasopharyngeal carcinoma (N P C) were treated again with radiation at our hospital. All cases were proven histologically by biopsy. Of these patients, 92 had their recurrence in the nasopharynx only, 13 had additional involvement of the base of the skull, and 7 had tumor recurrences simultaneously in the nasopharynx as well as the cervical lymph nodes. Radiotherapy adopted in this series was 60Co external irradiation (X R Te) and/ or betatron in 96 patients, X R Te plus intracavitary 60Co irradiation (X R Ti) in 12 patients and X R Ti alone in the other 4 patients. The 1-, 3-, and 5-year survival rates were 86.3%, 45.8% and 30.2% respectively after the start of recurrence retreatment. The 63 patients who survived for 5 years or more were analyzed. The prognosis of the patient was related to the histological type, clinical stage, modality of treatment, and disease interval to recurrence and site of recurrence. No serious complications occurred. It is suggested that re-irradiation is appropriate in the treatment of loco-regional recurrent N P C.展开更多
Of seventy-one patients with rectal cancer after radical resection retaining the anus, 15 developed local recurrence with a recurrence rate of 21.1%. Local recurrence was correlated with improper safety margin from th...Of seventy-one patients with rectal cancer after radical resection retaining the anus, 15 developed local recurrence with a recurrence rate of 21.1%. Local recurrence was correlated with improper safety margin from the lower edge of cancer to the anal end. There was statistical significant difference between 3 cm or more and 2 cm or less. The local recurrence was also related to the pathologic stage, histologic differentiation and implant of free cancer cells. It is suggested that the surgical indication of saving the anus be strict and without stretching, the safety margin from the lower edge of cancer to the anal end should not be less than 2 cm in early rectal cancer and not less than 4 cm in advanced lesions. During the operation, no touching tumor technique, thorough rinsing of the peritoneal cavity and pre- or post-operative radiotherapy are important for prevention of local recurrence. Early local recurrent rectal cancer can be detected by periodic examinations.展开更多
Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: N...Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.展开更多
By using the theories on Stokes multicolored water waves and taking the two- layer ocean as a basic model of stratified ocean, the paper analyzes the problems related to the effects of the nonlinear water wave on offs...By using the theories on Stokes multicolored water waves and taking the two- layer ocean as a basic model of stratified ocean, the paper analyzes the problems related to the effects of the nonlinear water wave on offshore structures. A mathematical expression is presented to describe second order wave radiation conditions. Using integral principle, the analytical integral solutions are given to evaluate second order scattered wave loads on general vertical circular cylinders in the two-layer ocean, and the special recurrence formulas for infinite integrals over free and stratified surfaces are derived.展开更多
Introduction: Breast cancer is the most common cancer in the Iranian female population, and the incidence of the disease is rising. Early detection in association with staging or grading the tumor is the most effectiv...Introduction: Breast cancer is the most common cancer in the Iranian female population, and the incidence of the disease is rising. Early detection in association with staging or grading the tumor is the most effective method to increase survival rates. Studies have revealed that cortactin overexpression may play a role in the final stages of tumor progression and affects invasion and cellular motility. The aim of this study is to evaluate cortactin gene expression among Iranian female patients with breast cancer. Materials and Methods: Samples belonging to 70 breast cancer patients were randomly selected from the Imam Khomeini tumor bank. Normal and tumor tissues were prepared and stored at -80°C. Cortactin gene expression was evaluated by real-time PCR. Finally the data, along with demographic and clinical parameters, were analyzed using Prism 5.0 software, followed by t-test and ANOVA analysis. Results: Cortactin gene expression among tumor tissues increased 95.71% in comparison with normal tissues. A significant correlation between cortactin gene expression and lymph nodes’ involvement (P = 0.0077) and tumor stage (P = 0.0030) was observed. However, tumor grade (P = 0.8598), tumor size (P = 0.3058), and patient’s age (P = 0.4135) had no significant correlation with the gene’s expression level. Discussion: This study demonstrated that the cortactin gene’s overexpression in breast cancer may enhance lymph nodes’ involvement. This study also found that the gene’s expression was raised significantly in progressed stages of the cancer. Therefore, cortactin gene overexpression is an important factor indicating breast cells’ invasion. Conclusion: The cortactin gene’s expression level can be considered an accurate indicator for female breast cancer and also an appropriate biomarker for this cancer in clinical evaluations.展开更多
This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, HA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of r...This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, HA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage Ⅱ the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.展开更多
The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence...The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases, the tumor has partial of total absence of ABO(H) antigens of tumor cell surface and could be accompanied with muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases from lower to higher grades. The morphometric grading system is able to make a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors.展开更多
Between October 1985 and June 1992 Postoperative kelolds of 125 Patients were treated with superficial X-ray (100-140 Kv) and electron beam (6 and 9 MeV ), in an attempt to prevent their recurrence, 100 patients with ...Between October 1985 and June 1992 Postoperative kelolds of 125 Patients were treated with superficial X-ray (100-140 Kv) and electron beam (6 and 9 MeV ), in an attempt to prevent their recurrence, 100 patients with 129 sites received a dose of 1200-4000 cGy at 200-300 cGy per fraction within one to four weeks and at intervals of one to three weeks between excision and irradiation. Rate of success In the prevention of kelold was only 28. 6% (37/ 129). However, 25 patients with 25 sites received a total dose of 1500 cGy at 500 cGy per fraction starting within one week after excision and at Intervals of 96 hours. The success rate was 84% (21/25).展开更多
With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyn...With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.展开更多
Objective To compare the outcomes of an invasive with a conservative strategy in the manage-ment of patients with non-ST-elevation acute coronary syndromes. Methods From January 2000 to June 2001, 505 patients present...Objective To compare the outcomes of an invasive with a conservative strategy in the manage-ment of patients with non-ST-elevation acute coronary syndromes. Methods From January 2000 to June 2001, 505 patients presenting with unstable angina or non-Q wave myocardial infarction were divided into two groups (conservative vs. invasive) according to management strategy. Patients assigned to an early invasive strategy underwent coronary angiography within 7d of enrollment after intensive antiplatelet, antithrombotic and antiangina therapy and revascularization as appropriate. All patients were followed up at least 6 months. The primary endpoints were cardiac death and acute myocardial infarction. Recurrence angina and readmission were the secondary end-point. Results There were 194 patients in conservative group and311 patients in invasive group. Overall, coronary angiography was performed in 100% and 56% , and revascularization in 93% and 52% in the invasive and conservative groups, respectively. During a mean of 11±5.7 months (range 6 ~ 24 months) of follow-up, the occurrence of primary endpoint was significantly lower in the invasive group than that in the conservative group (3.9% vs 8. 2% , P =0. 036). The rate of recurrent angina (48% vs 17% , P =0. 001) , readmission (41% vs 13% , P = 0. 001) and revascularization (12% vs 35% , P =0. 001) was also significantly lower in patients assigned to invasive strategy. Conclusion The study indicates that the early invasive approach may be the preferred strategy in patients with unstable angina or non-Q wave myocardial infarction.展开更多
Objectives To invest the success procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels. Methods 290 patien...Objectives To invest the success procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels. Methods 290 patients with selected or emergency stent implantation in small vessels from April, 1997 to March,2002. Total 299 vessels,304 lesions and 316 stents were statisted. The successs rate of procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels were assessed. The patients were followed up 1 month to 4 years. Re-catheter angiography were done in 122/290 patients. Results The narrow rate of lesion dropped from 89% ± 12% before procedure to 5% ±5% after procedure (diameter). 202 patients were followed up 1 month (69.7%). 197/202 cases were survival. 5/202 cases died in 3hrs to 7days. 2/5 cases died of persistent hypotension after procedure. 1/5 case died of acute left heart failure. 2/5 cases died of sudden death. 180 cases were followed up 5 months to 4 years. The non-event survival (NES) rate was 73.3% (132/180). The re-angiography were done in 122 cases. Restenosis happened in 39 cases (30.3%). 37 patients repeated PCI. 2 patients went to CABG. 2 cases got angina recurrence and were proved second time restenosis by re-angiography. The third time PCI was done in 1 patient. The other patients went to CABG. 1 case died of chronic heart failure after 2 years, 1 case suffered acute myocardial infarction on artery stent implanted. Conclusions There are high success rate of procedure and perfect immediate outcome in stent placement in small vessels. Main adverse cardiac events did not increased. Non-event survial was satisfied in long term follow -up. Restenosis rate was showed slightly higher than the one of main vessels.展开更多
Aim:This study aims to evaluate the feasibility of examining circulating tumor DNA(ctDNA)in urine samples from hepatocellular carcinoma(HCC)patients by droplet digital PCR(ddPCR)and to assess its value in predicting H...Aim:This study aims to evaluate the feasibility of examining circulating tumor DNA(ctDNA)in urine samples from hepatocellular carcinoma(HCC)patients by droplet digital PCR(ddPCR)and to assess its value in predicting HCC recurrence after surgery.Methods:HCC cases who accepted surgical resection were included.Perioperative urine,tissue and peripheral blood specimens were collected.Four hotspot mutants[TP53-rs28934571(c.747G>T),TRET-rs1242535815(c.1-124C>T),CTNNB1-rs121913412(c.121A>G),and CTNNB1-rs121913407(c.133T>C)]were chosen for ctDNA analysis,and mutant allele frequency(MAF)was worked out.Sanger sequencing was performed on matched tumor tissues and peripheral blood mononuclear cells(PBMCs).The patients’clinicopathologic characteristics were retrospectively analyzed.The predictive abilities of urine ctDNA for postoperative recurrence were evaluated using the Kaplan-Meier method.Results:Forty-six patients were enrolled,and 18 patients(39.1%,18/46)exhibited detectable circulating mutants,with the MAF in the range of 0.07%to 0.91%.The consistency test indicated moderate to substantial concordance between urine and paired tumor tissue mutations.The mutation level dropped dramatically or disappeared after surgery.Positive urine ctDNA before surgery was closely related to greater tumor size and recurrence.Kaplan-Meier curves revealed significantly shorter disease-free survival(DFS)for ctDNA-positive patients.Multivariate analysis identified detectable urine ctDNA as an independent risk factor for tumor recurrence.More than that,receiver operating characteristic(ROC)curves demonstrated that urine ctDNA had the largest area under the curve(AUC)for predicting HCC recurrence.Conclusion:Detecting ctDNA in urine using ddPCR is feasible and holds significant potential for predicting and monitoring HCC recurrence.展开更多
Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is ...Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is well-established,the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+T cell-mediated antitumor immunity remain unclear.Our findings indicate that depleting SRSF1 in CD8+T cells improve antitumor immune function,glycolytic metabolism,and the efficacy of adoptive T cell therapy.The inactivation of SRSF1 in tumor cells reduces transcription factors,including c-Jun,c-myc,and JunB,facilitating glycolytic metabolism reprogramming,which restores CD8+T cell function and inhibits tumor growth.The small-molecule inhibitor TN2008 targets SRSF1,boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models.We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+T cells.展开更多
This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metast...This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metastasis:32;with metastasis:5;recurrence:8)27 gastric ulcer,展开更多
Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the devel...Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely unknown.Here,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat iCCA.Methods:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome anal-ysis.Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was determined.Survival and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic subtypes.Cell proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA cells.Results:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were identified.These metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic alterations.The S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)mutations.Among the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)signaling.Conclusion:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing that the S2 subtype exhibited the poorest survival outcomes.We further identified DGKA as a potential target for the S2 subtype.展开更多
Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel bl...Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.展开更多
Background:The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma(HCC)remains poor.Although serine-and arginine-rich splicing factor(SRSF)family members play crucial roles in tumo...Background:The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma(HCC)remains poor.Although serine-and arginine-rich splicing factor(SRSF)family members play crucial roles in tumors,their impact on tumor immunology remains unclear.This study aimed to elucidate the role of SRSF10 in HCC immunotherapy.Methods:To identify the key genes associated with immunotherapy resistance,we conducted single-nuclear RNA sequencing,multiplex immunofluorescence,and The Cancer Genome Atlas and Gene Expression Omnibus database analyses.We investigated the biological functions of SRSF10 in immune evasion using in vitro co-culture systems,flow cytometry,various tumor-bearing mouse models,and patient-derived organotypic tumor spheroids.Results:SRSF10 was upregulated in various tumors and associated with poor prognosis.Moreover,SRSF10 positively regulated lactate production,and SRSF10/glycolysis/histone H3 lysine 18 lactylation(H3K18la)formed a positive feedback loop in tumor cells.Increased lactate levels promoted M2 macrophage polarization,thereby inhibiting CD8^(+)T cell activity.Mechanistically,SRSF10 interacted with the 3′-untranslated region of MYB,enhancing MYB RNA stability,and subsequently upregulating key glycolysis-related enzymes including glucose transporter 1(GLUT1),hexokinase 1(HK1),lactate dehydrogenase A(LDHA),resulting in elevated intracellular and extracellular lactate levels.Lactate accumulation induced histone lactylation,which further upregulated SRSF10 expression.Additionally,lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages,thereby activating transcription and enhancing pro-tumor macrophage activity.M2 macrophages,in turn,inhibited the enrichment of CD8^(+)T cells and the proportion of interferon-γ+CD8^(+)T cells in the tumor microenvironment(TME),thus creating an immunosuppressive TME.Clinically,SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors.Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1(PD-1)monoclonal antibodies(mAbs)in both murine and human preclinical models.Conclusions:The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti-PD-1 resistance.Inhibiting SRSF10 by 1C8 may overcome anti-PD-1 tolerance in HCC.展开更多
Despite the notable efficacy of anti-PD1 therapy in the management of hepatocellular carcinoma(HCC)patients,resistance in most individuals necessitates additional investigation.For this study,we collected tumor tissue...Despite the notable efficacy of anti-PD1 therapy in the management of hepatocellular carcinoma(HCC)patients,resistance in most individuals necessitates additional investigation.For this study,we collected tumor tissues from nine HCC patients receiving anti-PD1 monotherapy and conducted RNA sequencing.These findings revealed significant upregulation of GSDME,which is predominantly expressed by tumor-associated macrophages(TAMs),in anti-PD1-resistant patients.Furthermore,patients with elevated levels of GSDME+macrophages in HCC tissues presented a poorer prognosis.The analysis of single-cell sequencing data and flow cytometry revealed that the suppression of GSDME expression in nontumor cells resulted in a decrease in the proportion of M2-like macrophages within the tumor microenvironment(TIME)of HCC while concurrently augmenting the cytotoxicity of CD8+T cells.The non-N-terminal fragment of GSDME within macrophages combines with PDPK1,thereby activating the PI3K-AKT pathway and facilitating M2-like polarization.The small-molecule Eliprodil inhibited the increase in PDPK1 phosphorylation mediated by GSDME site 1.The combination of Eliprodil and anti-PD1 was effective in the treatment of both spontaneous HCC in c-Myc+/+;Alb-Cre+/+mice and in a hydrodynamic tail vein injection model,which provides a promising strategy for novel combined immunotherapy.展开更多
Ⅰ. INTRODUCTION At the 1978 ICM conference held in Helsinki, Ap?ry gave a proof of ζ(3)=Σ1/N^3 being irrational. For this purpose he introduced the numbers α_n (n≥0) defined by recurrence
In human and other mammalian populations there are many inheritable traits that do not appear to have gross phenotypic effects. These normal variations occur more frequently than that as expected from recurrent mutati...In human and other mammalian populations there are many inheritable traits that do not appear to have gross phenotypic effects. These normal variations occur more frequently than that as expected from recurrent mutation rates alone. With the展开更多
文摘From 1975 to 1987, 112 patients with loco-regional recurrence of nasopharyngeal carcinoma (N P C) were treated again with radiation at our hospital. All cases were proven histologically by biopsy. Of these patients, 92 had their recurrence in the nasopharynx only, 13 had additional involvement of the base of the skull, and 7 had tumor recurrences simultaneously in the nasopharynx as well as the cervical lymph nodes. Radiotherapy adopted in this series was 60Co external irradiation (X R Te) and/ or betatron in 96 patients, X R Te plus intracavitary 60Co irradiation (X R Ti) in 12 patients and X R Ti alone in the other 4 patients. The 1-, 3-, and 5-year survival rates were 86.3%, 45.8% and 30.2% respectively after the start of recurrence retreatment. The 63 patients who survived for 5 years or more were analyzed. The prognosis of the patient was related to the histological type, clinical stage, modality of treatment, and disease interval to recurrence and site of recurrence. No serious complications occurred. It is suggested that re-irradiation is appropriate in the treatment of loco-regional recurrent N P C.
文摘Of seventy-one patients with rectal cancer after radical resection retaining the anus, 15 developed local recurrence with a recurrence rate of 21.1%. Local recurrence was correlated with improper safety margin from the lower edge of cancer to the anal end. There was statistical significant difference between 3 cm or more and 2 cm or less. The local recurrence was also related to the pathologic stage, histologic differentiation and implant of free cancer cells. It is suggested that the surgical indication of saving the anus be strict and without stretching, the safety margin from the lower edge of cancer to the anal end should not be less than 2 cm in early rectal cancer and not less than 4 cm in advanced lesions. During the operation, no touching tumor technique, thorough rinsing of the peritoneal cavity and pre- or post-operative radiotherapy are important for prevention of local recurrence. Early local recurrent rectal cancer can be detected by periodic examinations.
文摘Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8% , focal absorption effective rate 91. 3% , cavity closing rate 58. 7% and 10-day symptom improving rate 54. 4% , while in the control group, the corresponding rates were 65.2% , 73. 9 % , 37.0% and 26.1 % , respectively. Comparison between the groups showed significant difference in all the parameters (P<0.05, P<0.05, P<0.05 and P<0.01). The incidence of adverse reaction and 2-year bacteriological recurrence rate in the treated group were 23. 9% and 2.6% respectively, while those in the control group 50. 0% and 16. 7% , which were higher than the former group with significant difference ( P<0. 01 and P<0. 05, respectively). Conclusion: The therapeutic effect of combined treatment with anti-TB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.
基金National Natural Science Foundation of China (19802023)
文摘By using the theories on Stokes multicolored water waves and taking the two- layer ocean as a basic model of stratified ocean, the paper analyzes the problems related to the effects of the nonlinear water wave on offshore structures. A mathematical expression is presented to describe second order wave radiation conditions. Using integral principle, the analytical integral solutions are given to evaluate second order scattered wave loads on general vertical circular cylinders in the two-layer ocean, and the special recurrence formulas for infinite integrals over free and stratified surfaces are derived.
文摘Introduction: Breast cancer is the most common cancer in the Iranian female population, and the incidence of the disease is rising. Early detection in association with staging or grading the tumor is the most effective method to increase survival rates. Studies have revealed that cortactin overexpression may play a role in the final stages of tumor progression and affects invasion and cellular motility. The aim of this study is to evaluate cortactin gene expression among Iranian female patients with breast cancer. Materials and Methods: Samples belonging to 70 breast cancer patients were randomly selected from the Imam Khomeini tumor bank. Normal and tumor tissues were prepared and stored at -80°C. Cortactin gene expression was evaluated by real-time PCR. Finally the data, along with demographic and clinical parameters, were analyzed using Prism 5.0 software, followed by t-test and ANOVA analysis. Results: Cortactin gene expression among tumor tissues increased 95.71% in comparison with normal tissues. A significant correlation between cortactin gene expression and lymph nodes’ involvement (P = 0.0077) and tumor stage (P = 0.0030) was observed. However, tumor grade (P = 0.8598), tumor size (P = 0.3058), and patient’s age (P = 0.4135) had no significant correlation with the gene’s expression level. Discussion: This study demonstrated that the cortactin gene’s overexpression in breast cancer may enhance lymph nodes’ involvement. This study also found that the gene’s expression was raised significantly in progressed stages of the cancer. Therefore, cortactin gene overexpression is an important factor indicating breast cells’ invasion. Conclusion: The cortactin gene’s expression level can be considered an accurate indicator for female breast cancer and also an appropriate biomarker for this cancer in clinical evaluations.
文摘This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, HA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage Ⅱ the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.
文摘The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases, the tumor has partial of total absence of ABO(H) antigens of tumor cell surface and could be accompanied with muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases from lower to higher grades. The morphometric grading system is able to make a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors.
文摘Between October 1985 and June 1992 Postoperative kelolds of 125 Patients were treated with superficial X-ray (100-140 Kv) and electron beam (6 and 9 MeV ), in an attempt to prevent their recurrence, 100 patients with 129 sites received a dose of 1200-4000 cGy at 200-300 cGy per fraction within one to four weeks and at intervals of one to three weeks between excision and irradiation. Rate of success In the prevention of kelold was only 28. 6% (37/ 129). However, 25 patients with 25 sites received a total dose of 1500 cGy at 500 cGy per fraction starting within one week after excision and at Intervals of 96 hours. The success rate was 84% (21/25).
文摘With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.
文摘Objective To compare the outcomes of an invasive with a conservative strategy in the manage-ment of patients with non-ST-elevation acute coronary syndromes. Methods From January 2000 to June 2001, 505 patients presenting with unstable angina or non-Q wave myocardial infarction were divided into two groups (conservative vs. invasive) according to management strategy. Patients assigned to an early invasive strategy underwent coronary angiography within 7d of enrollment after intensive antiplatelet, antithrombotic and antiangina therapy and revascularization as appropriate. All patients were followed up at least 6 months. The primary endpoints were cardiac death and acute myocardial infarction. Recurrence angina and readmission were the secondary end-point. Results There were 194 patients in conservative group and311 patients in invasive group. Overall, coronary angiography was performed in 100% and 56% , and revascularization in 93% and 52% in the invasive and conservative groups, respectively. During a mean of 11±5.7 months (range 6 ~ 24 months) of follow-up, the occurrence of primary endpoint was significantly lower in the invasive group than that in the conservative group (3.9% vs 8. 2% , P =0. 036). The rate of recurrent angina (48% vs 17% , P =0. 001) , readmission (41% vs 13% , P = 0. 001) and revascularization (12% vs 35% , P =0. 001) was also significantly lower in patients assigned to invasive strategy. Conclusion The study indicates that the early invasive approach may be the preferred strategy in patients with unstable angina or non-Q wave myocardial infarction.
文摘Objectives To invest the success procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels. Methods 290 patients with selected or emergency stent implantation in small vessels from April, 1997 to March,2002. Total 299 vessels,304 lesions and 316 stents were statisted. The successs rate of procedure, immediate outcome after procedure, the rate of main adverse cardiac events after procedure and restenosis after stent placement in small coronary vessels were assessed. The patients were followed up 1 month to 4 years. Re-catheter angiography were done in 122/290 patients. Results The narrow rate of lesion dropped from 89% ± 12% before procedure to 5% ±5% after procedure (diameter). 202 patients were followed up 1 month (69.7%). 197/202 cases were survival. 5/202 cases died in 3hrs to 7days. 2/5 cases died of persistent hypotension after procedure. 1/5 case died of acute left heart failure. 2/5 cases died of sudden death. 180 cases were followed up 5 months to 4 years. The non-event survival (NES) rate was 73.3% (132/180). The re-angiography were done in 122 cases. Restenosis happened in 39 cases (30.3%). 37 patients repeated PCI. 2 patients went to CABG. 2 cases got angina recurrence and were proved second time restenosis by re-angiography. The third time PCI was done in 1 patient. The other patients went to CABG. 1 case died of chronic heart failure after 2 years, 1 case suffered acute myocardial infarction on artery stent implanted. Conclusions There are high success rate of procedure and perfect immediate outcome in stent placement in small vessels. Main adverse cardiac events did not increased. Non-event survial was satisfied in long term follow -up. Restenosis rate was showed slightly higher than the one of main vessels.
基金supported by National Natural Science Foundation of China(82150004)Shanghai Municipal Health Commission(20224Y0285,R2022-010)+4 种基金Shanghai“Rising Stars of Medical Talent”Youth Development Program(Outstanding Youth Medical Talents)the Projects from the Shanghai Science and Technology Commission(19441905000 and 21140900300)Natural Science Funds of Shanghai(21ZR1413800,20ZR1473100)the Projects from Science Foundation of Zhongshan Hospital,Fudan University(2021ZSCX28,2020ZSLC31)the Shanghai Municipal Science and Technology Major Project,and the Shanghai Municipal Key Clinical Specialty.
文摘Aim:This study aims to evaluate the feasibility of examining circulating tumor DNA(ctDNA)in urine samples from hepatocellular carcinoma(HCC)patients by droplet digital PCR(ddPCR)and to assess its value in predicting HCC recurrence after surgery.Methods:HCC cases who accepted surgical resection were included.Perioperative urine,tissue and peripheral blood specimens were collected.Four hotspot mutants[TP53-rs28934571(c.747G>T),TRET-rs1242535815(c.1-124C>T),CTNNB1-rs121913412(c.121A>G),and CTNNB1-rs121913407(c.133T>C)]were chosen for ctDNA analysis,and mutant allele frequency(MAF)was worked out.Sanger sequencing was performed on matched tumor tissues and peripheral blood mononuclear cells(PBMCs).The patients’clinicopathologic characteristics were retrospectively analyzed.The predictive abilities of urine ctDNA for postoperative recurrence were evaluated using the Kaplan-Meier method.Results:Forty-six patients were enrolled,and 18 patients(39.1%,18/46)exhibited detectable circulating mutants,with the MAF in the range of 0.07%to 0.91%.The consistency test indicated moderate to substantial concordance between urine and paired tumor tissue mutations.The mutation level dropped dramatically or disappeared after surgery.Positive urine ctDNA before surgery was closely related to greater tumor size and recurrence.Kaplan-Meier curves revealed significantly shorter disease-free survival(DFS)for ctDNA-positive patients.Multivariate analysis identified detectable urine ctDNA as an independent risk factor for tumor recurrence.More than that,receiver operating characteristic(ROC)curves demonstrated that urine ctDNA had the largest area under the curve(AUC)for predicting HCC recurrence.Conclusion:Detecting ctDNA in urine using ddPCR is feasible and holds significant potential for predicting and monitoring HCC recurrence.
基金funded by the National Natural Science Foundation of China(Grant No.).This research was supported by grants from the National Natural Science Foundation of China(Grant Nos.82073217,82403555,82073218,82003084)the National Key Research and Development Program of China(Grant No.2018YFC1312100)+3 种基金the Shanghai Municipal Key Clinical Specialty,and the CAMS Innovation Fund for Medical Sciences(CIFMS 2019-I2M-5-058)the Leading Project of the Science and Technology Commission of Shanghai Municipality(No.21Y21900100)the Project of the Shanghai Municipal Health Commission This research was also supported by the Outstanding Resident Clinical Postdoctoral Program at Zhongshan Hospital,Fudan University,and the China Postdoctoral Science Foundation(KLF152165,202140269)The authors appreciated for the technical assistance in the virtual screening job described in this study by Prof.Renxiao Wang,School of Pharmacy,Fudan University.
文摘Serine arginine-rich splicing factor 1(SRSF1)is a key oncogenic splicing factor in various cancers,promoting abnormal gene expression through post-translational regulation.Although the protumoral function of SRSF1 is well-established,the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+T cell-mediated antitumor immunity remain unclear.Our findings indicate that depleting SRSF1 in CD8+T cells improve antitumor immune function,glycolytic metabolism,and the efficacy of adoptive T cell therapy.The inactivation of SRSF1 in tumor cells reduces transcription factors,including c-Jun,c-myc,and JunB,facilitating glycolytic metabolism reprogramming,which restores CD8+T cell function and inhibits tumor growth.The small-molecule inhibitor TN2008 targets SRSF1,boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models.We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+T cells.
文摘This is China’s pilot stndy in the assessment of the diagnostic value of serum soluble IL-2 receptor (sIL-2R) in gastric cancer.We measured its level by ELISA method in 45 patients with gastric cancer (without metastasis:32;with metastasis:5;recurrence:8)27 gastric ulcer,
基金This project was supported by grants from the National Natural Science Foundation of China(82273387,82273386,82073217,32270711,82073218 and 82003084)the National Key Research and Develop-ment Program of China(2018YFC1312100)+3 种基金Beijing Nova Program(20220484230)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Shanghai Municipal Key Clinical Specialty,CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-058)the State Key Laboratory of Proteomics(SKLP-K202004).
文摘Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic strategies.The metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely unknown.Here,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat iCCA.Methods:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome anal-ysis.Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was determined.Survival and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic subtypes.Cell proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA cells.Results:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were identified.These metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic alterations.The S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)mutations.Among the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)signaling.Conclusion:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing that the S2 subtype exhibited the poorest survival outcomes.We further identified DGKA as a potential target for the S2 subtype.
文摘Four calcium channel blockers, i.e. nifedipine, verapamil, cinnarizine and tetrandrine are currently available and used widely in treating cardiovascular diseases. To confirm the effects, if any, of calcium channel blockers on cirrhotic patients with portal hypertension, a study was performed on esophageal variceal pressure and rebleeding rate of esophageal varices after 2 years by using calcium channel blocker in 321 patients from some 23 hospitals. The results demonstrated that the calcium channel blockers could significantly reduce the esophageal variceal pressure and the portal blood flow in cirrhotic patients with portal hypertension. The proportion of patients with no recurrent gastrointestinal bleeding after 2 years medication of tetrandrine was 87.9% in tetrandrine group, significantly higher than those in the other 4 groups (P<0.05). It is suggested that tetrandrine should be more effective for cirrhotic patients with portal hypertension in preventing recurrent variceal bleeding.
基金supported by the National Natural Science Foundation of China(No.82372946 and No.82072670)the 12 Leading Project of the Science and Technology Committee of Shanghai Municipality(No.21Y21900100)the Project of Shanghai Municipal Health Commission(No.202140269).
文摘Background:The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma(HCC)remains poor.Although serine-and arginine-rich splicing factor(SRSF)family members play crucial roles in tumors,their impact on tumor immunology remains unclear.This study aimed to elucidate the role of SRSF10 in HCC immunotherapy.Methods:To identify the key genes associated with immunotherapy resistance,we conducted single-nuclear RNA sequencing,multiplex immunofluorescence,and The Cancer Genome Atlas and Gene Expression Omnibus database analyses.We investigated the biological functions of SRSF10 in immune evasion using in vitro co-culture systems,flow cytometry,various tumor-bearing mouse models,and patient-derived organotypic tumor spheroids.Results:SRSF10 was upregulated in various tumors and associated with poor prognosis.Moreover,SRSF10 positively regulated lactate production,and SRSF10/glycolysis/histone H3 lysine 18 lactylation(H3K18la)formed a positive feedback loop in tumor cells.Increased lactate levels promoted M2 macrophage polarization,thereby inhibiting CD8^(+)T cell activity.Mechanistically,SRSF10 interacted with the 3′-untranslated region of MYB,enhancing MYB RNA stability,and subsequently upregulating key glycolysis-related enzymes including glucose transporter 1(GLUT1),hexokinase 1(HK1),lactate dehydrogenase A(LDHA),resulting in elevated intracellular and extracellular lactate levels.Lactate accumulation induced histone lactylation,which further upregulated SRSF10 expression.Additionally,lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages,thereby activating transcription and enhancing pro-tumor macrophage activity.M2 macrophages,in turn,inhibited the enrichment of CD8^(+)T cells and the proportion of interferon-γ+CD8^(+)T cells in the tumor microenvironment(TME),thus creating an immunosuppressive TME.Clinically,SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors.Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1(PD-1)monoclonal antibodies(mAbs)in both murine and human preclinical models.Conclusions:The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti-PD-1 resistance.Inhibiting SRSF10 by 1C8 may overcome anti-PD-1 tolerance in HCC.
基金supported by the National Natural Science Foundation of China(No.82372946,No.82072670,and No.81871916)the Leading Project of the Science and Technology Committee of Shanghai Municipality(No.21Y21900100)the Project of Shanghai Municipal Health Commission(No.202140269).
文摘Despite the notable efficacy of anti-PD1 therapy in the management of hepatocellular carcinoma(HCC)patients,resistance in most individuals necessitates additional investigation.For this study,we collected tumor tissues from nine HCC patients receiving anti-PD1 monotherapy and conducted RNA sequencing.These findings revealed significant upregulation of GSDME,which is predominantly expressed by tumor-associated macrophages(TAMs),in anti-PD1-resistant patients.Furthermore,patients with elevated levels of GSDME+macrophages in HCC tissues presented a poorer prognosis.The analysis of single-cell sequencing data and flow cytometry revealed that the suppression of GSDME expression in nontumor cells resulted in a decrease in the proportion of M2-like macrophages within the tumor microenvironment(TIME)of HCC while concurrently augmenting the cytotoxicity of CD8+T cells.The non-N-terminal fragment of GSDME within macrophages combines with PDPK1,thereby activating the PI3K-AKT pathway and facilitating M2-like polarization.The small-molecule Eliprodil inhibited the increase in PDPK1 phosphorylation mediated by GSDME site 1.The combination of Eliprodil and anti-PD1 was effective in the treatment of both spontaneous HCC in c-Myc+/+;Alb-Cre+/+mice and in a hydrodynamic tail vein injection model,which provides a promising strategy for novel combined immunotherapy.
文摘Ⅰ. INTRODUCTION At the 1978 ICM conference held in Helsinki, Ap?ry gave a proof of ζ(3)=Σ1/N^3 being irrational. For this purpose he introduced the numbers α_n (n≥0) defined by recurrence
文摘In human and other mammalian populations there are many inheritable traits that do not appear to have gross phenotypic effects. These normal variations occur more frequently than that as expected from recurrent mutation rates alone. With the
