Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- a...Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- anism. Here, we determined that spared nerve injury （SNI） increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia （DRG） neurons and satellite glial cells. SNI also induced long- lasting upregulation of CXCL12 and CXCR4 in the ipsi- lateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI- induced a sustained increase in TNF-α expression in the DRG and spinal cord. Intraperitoneal injection （i.p.） of the TNF-α synthesis inhibitor thalidomide reduced the SNI-in- duced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection （i.t.） of the CXCR4 antagonist AMD3100, both 30 rain before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. admin- istration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the acti- vation of ERK in the spinal cord. The mechanical hyper- sensitivity induced in nai＇ve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-α might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL 12/CXCR4 sig- naling via ERK activation contributes to the development and maintenance of neuropathic pain.展开更多
Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays...Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.展开更多
Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodyn...Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1(Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury(SNI).Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in na¨?ve but also in ML133-pretreated mice. In contrast, bicuculline, a GABAAreceptor antagonist, induced only punctate, but not dynamic,allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents(gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration oracute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively.In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.展开更多
The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological condition...The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.展开更多
Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to si...Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.展开更多
Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the t...Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the three terminal branches of the sciatic nerve of rats (tibial and common peroneal nerves) leaving the sural nerve intact. Continuous intrathe-cal administration of propentofylline, a glial modulating agent, 1 d before and 5 d after operation, was performed to disrupt spinal cord glia function. The vehicle was intrathecally administrated as control. The paw withdrawal threshold to mechanical stimulation (paw withdrawal mechaical threshold PWMT), body mass and motor function were determined pre- and post-surgery. Results: It produced a prolonged mechanical allodynia in the medial and lateral part of the ipsilateral hind paw in SNL models. The treatment with propentofylline significantly prevented the development of mechanical allodynia located in either medial or lateral plantar surface. Rats in two groups showed normal motor function and body weight increase. Conclusion: SNI model can be applied as a useful method with little variance in searching the mechanism of neuropathic pain. These study suggest that spinal glia activation may contribute to mechanical allodynia induced by SNI.展开更多
Tumor recurrence, the Gordian knot of liver transplantation for malignancies, may be attributed to many parameters. The technique of the “classical” recipient hepatectomy is believed to be one of the potential reaso...Tumor recurrence, the Gordian knot of liver transplantation for malignancies, may be attributed to many parameters. The technique of the “classical” recipient hepatectomy is believed to be one of the potential reasons to cause tumor evasion because of the possible increase of circulating tumor cells, thus leading to an increased recurrent rate. On this background, the no-touch oncological recipient hepatectomy technique has been developed. A comprehensive review of the development and the key surgical steps of the no-touch recipient hepatectomy is presented. This technique might improve clinical outcomes, especially for those recipients who are at a high risk for tumor recurrence. Multicenter prospective studies should be set up to further validate the prognostic role of this technique in patients with liver cancer treated with liver transplantation.展开更多
BACKGROUND Laparoscopic nephrectomy is a preferred surgical approach due to its minimally invasive nature and faster recovery times.However,effective management of postoperative pain remains a significant challenge.Se...BACKGROUND Laparoscopic nephrectomy is a preferred surgical approach due to its minimally invasive nature and faster recovery times.However,effective management of postoperative pain remains a significant challenge.Several traditional methods,including opioid-based analgesia,are commonly used but are associated with side effects such as nausea,vomiting,sedation,and delayed recovery.In recent years,the erector spinae plane block(ESPB)has gained attention as an ultrasoundguided regional anesthesia technique offering promising results in various surgical procedures by reducing opioid requirements and enhancing patient comfort.AIM To evaluate the efficacy and safety of ESPB in comparison to conventional pain management strategies in patients undergoing laparoscopic nephrectomy.METHODS Following PRISMA guidelines,we searched PubMed,EMBASE,Web of Science,and the Cochrane Register for randomized controlled trials(RCTs)comparing ESPB with control for laparoscopic nephrectomy.The Cochrane Risk of Bias tool was employed for quality assessment.The primary outcome was total patient-controlled analgesia(PCA)consumption.Secondary outcomes included hospital discharge time and the incidence of postoperative nausea and vomiting.A random-effects meta-analysis was conducted to calculate pooled mean differences(MD)and odds ratios(OR)with 95%CIs.RESULTS Nine RCTs involving a total of 643 patients(ESPB group=320;control group=323)were included in the analysis.ESPB significantly reduced PCA opioid consumption compared to controls(MD:-14.24,95%CI:-20.66 to-7.83,P<0.0001).Subgroup analysis showed reduced PCA use with ESPB vs morphine(MD:-8.78,95%CI:-15.34 to-2.22,P=0.009),and a non-significant effect compared to other analgesics(MD:-48.26,95%CI:-143.60 to 47.09).No statistically significant differences were observed in discharge time or the incidence of nausea and vomiting.CONCLUSION ESPB demonstrates the potential of reducing PCA in laparoscopic nephrectomy patients;however,its impact on secondary outcomes remains inconclusive.Large-scale RCTs are needed to confirm ESPB's benefits and explore long-term effects.展开更多
BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate ...BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate early postoperative recovery.However,conventional minimally invasive plate osteosynthesis(MIPO)techniques frequently necessitate multiple(3-4)intraoperative fluoroscopic adjustments to achieve optimal plate positioning,which can inadvertently damage the PQ muscle.Based on our clinical observations,we developed a novel 3-point positioning technique to minimize PQ injury while ensuring accurate plate placement.Preliminary results demonstrate promising early clinical outcomes.AIM To retrospectively analyze distal radius fractures treated using the 3-point positioning-assisted MIPO technique with preservation of the PQ.METHODS The 3-point positioning technique was applied:The Kirschner wire was inserted after fluoroscopy and was correctly adjusted the position of the plate above the PQ.With the aid of Kirschner wires positioning the PQ stripping was performed only once,and the plate then placed in a correct and satisfactory position.Operation time,incision length,wrist pain score,upper extremity function disabilities of the arm,shoulder and hand(DASH)score,wrist Gartland-Werley score,wrist grip strength,and range of motion were among the quantitative variables recorded.Qualitative variables including AO fracture classification,intraoperative and postoperative complications were evaluated.RESULTS At a mean follow-up of 6.9±0.8 months,the mean scar length was 25.4±1.5 mm,the pain score was 0.7±0.6,the DASH score for the upper limb was 4.7±1.3,and the Gartland-Werley score for wrist function was 4.1±1.1 at the last follow-up.Mean flexion was 97.3%,extension was 97.0%,pronation was 98.9%,supination was 98.9%,and grip strength was 86.6%compared to contralateral values.No unfavorable intraoperative or postoperative complications occurred.CONCLUSION The 3-point positioning technique may reduce the damage to the PQ muscle and is a safe and effective method for MIPO for distal radius fractures.展开更多
On July 17,2024,Chinese electric vehicle manufacturer GAC International opened a smart factory in Rayong Province,Thailand.The next day,then Prime Minister of Thailand Saita Thawaixin met with a delegation led by Zeng...On July 17,2024,Chinese electric vehicle manufacturer GAC International opened a smart factory in Rayong Province,Thailand.The next day,then Prime Minister of Thailand Saita Thawaixin met with a delegation led by Zeng Qinghong,chairman of GAC Group.He encouraged GAC to purchase various spare parts in Thailand to enhance Thailand’s position in the global electric vehicle industry supply chain.“Thailand has a favorable business environment,”Zeng responded.“As the location of GAC’s first wholly-owned overseas facility,it was our premier choice.”展开更多
Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,a...Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,and incomplete emptying),storage(e.g.,frequency,urgency,urge incontinence,and nocturia),or a combination of both[2].Untreated PBNO can lead to bladder dysfunction,bladder diverticula,hydronephrosis,and impaired renal function[3].展开更多
Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracosc...Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracoscopic surgery (VATS) was carried out under general anesthesia. A double lumen endobronchial tube was intubated into trachea. One lung ventilation of the healthy side was done during operation. An incision of 8–10 cm long was made along the 4th or 5th intercostals. The lobectomy could be performed under VATS. Radionuclide colloid 32P was injected locally into the area where surgical cleaning of lymph node around was considered to be unsatisfactory or desection of the tumor was not completed. Results: The operation with VEMAST was successful in 29 patients. A conventional lobectomy by thoracotomy had to be done due to unusual bleeding from the pulmonary artery involved during VEMAST in one case and the procedure was interrupted because the pulmonary artery cloud not be separated from the tumor in another patient. There was no dead case or the patient who had any severe complication or adverse response to the radiant. Conclusion: Radionuclide therapy was performed to the treatment of stage II lung cancer with VEMAST in case that surgical resection was considered not to be satisfactory. Minithoractomy assisted with VATS lobectomy and radionuclide colloid 32P therapy is a safe and e?ective technique for some selected stage II lung cancer.展开更多
Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares...Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the （s-1, s） and （R, Q） inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets：one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model＇s correctness, method＇s validity as well as optimization project＇s rationality are proved to a certain extent.展开更多
Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair...Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.展开更多
The gold standard for curative treatment of locally advanced rectal cancer involves radical resection with a total mesorectal excision(TME). TME is the most effective treatment strategy to reduce local recurrence and ...The gold standard for curative treatment of locally advanced rectal cancer involves radical resection with a total mesorectal excision(TME). TME is the most effective treatment strategy to reduce local recurrence and improve survival outcomes regardless of the surgical platform used. However, there are associated morbidities, functional consequences, and quality of life(QoL) issues associated with TME; these risks must be considered during the modern-day multidisciplinary treatment for rectal cancer. This has led to the development of new surgical techniques to improve patient, oncologic, and QoL outcomes. In this work, we review the evolution of TME to the transanal total mesorectal excision(TaTME) through more traditional minimally invasive platforms. The review the development, safety and feasibility, proposed benefits and risks of the procedure, implementation and education models, and future direction for research and implementation of the TaTME in colorectal surgery. While satisfactory short-term results have been reported, the procedure is in its infancy, and long term outcomes and definitive results from controlled trials are pending.As evidence for safety and feasibility accumulates,structured training programs to standardize teaching,training, and safe expansion will aid the safe spread of the TaTME.展开更多
基金supported by grants from the National Natural Science Foundation of China(31171070,81171060,81501070and 81571079)
文摘Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mech- anism. Here, we determined that spared nerve injury （SNI） increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia （DRG） neurons and satellite glial cells. SNI also induced long- lasting upregulation of CXCL12 and CXCR4 in the ipsi- lateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNI- induced a sustained increase in TNF-α expression in the DRG and spinal cord. Intraperitoneal injection （i.p.） of the TNF-α synthesis inhibitor thalidomide reduced the SNI-in- duced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection （i.t.） of the CXCR4 antagonist AMD3100, both 30 rain before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. admin- istration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the acti- vation of ERK in the spinal cord. The mechanical hyper- sensitivity induced in nai＇ve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-α might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL 12/CXCR4 sig- naling via ERK activation contributes to the development and maintenance of neuropathic pain.
基金National Natural Science Foundation of China,No.819 73305 (to ZQ)Science and Technology Planning Project of Guangzhou of China,No.20190401 0487 (to ZQ)+1 种基金Natural Science Foundation of Guangdong Province,China,No.2021A1515010897 (to TT)Discipline Construction Fund of Cen tral Peoples Hospital of Zhanjiang,Nos.2020A01 (to TT) and 2020A02 (to TT)。
文摘Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuro pathic pain.N6-methyladenosine(m6A)is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases.However,the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown.In this study,we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve.High-throughput methylated RNA immunoprecipitation sequencing res ults showed that after spared nerve injury,there were 55 m6A methylated and diffe rentially expressed genes in the spinal cord.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway results showed that m6A modification triggered inflammatory responses and apoptotic processes in the early stages after spared nerve injury.Over time,the diffe rential gene function at postoperative day 7 was enriched in "positive regulation of neurogenesis" and "positive regulation of neural precursor cell prolife ration." These functions suggested that altered synaptic morphological plasticity was a turning point in neuropathic pain formation and maintenance.Results at postoperative day 14 suggested that the persistence of neuropathic pain might be from lipid metabolic processes,such as "very-low-density lipoprotein particle clearance," "negative regulation of choleste rol transport" and "membrane lipid catabolic process." We detected the expression of m6A enzymes and found elevated mRNA expression of Ythdf2 and Ythdf3 after spared nerve injury modeling.We speculate that m6A reader enzymes also have an important role in neuropathic pain.These results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at diffe rent stages after injury.
基金supported by grants from the National Natural Science Foundation of China (31771188 and 31471027)the Science and Technology Commission of Shanghai Municipality, China (13DJ1400302)
文摘Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brushevoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1(Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury(SNI).Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in na¨?ve but also in ML133-pretreated mice. In contrast, bicuculline, a GABAAreceptor antagonist, induced only punctate, but not dynamic,allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents(gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration oracute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively.In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.
基金partially supported by the MBRS-RISE Program(R25 GM061838)MBRS-SCORE(SO6-GM08224)+2 种基金COBRE(5P20-GM103642)SNRP(NS39405)RCMI(8G12MD007600)
文摘The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2015RIDIAIA01059432)
文摘Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.
文摘Objective: To investigate the role of spinal glial cells activation in neuropathic pain in a recently developed spared nerve injury (SNI) animal model by Decosterd and Woolf. Methods: A lesion was made to two of the three terminal branches of the sciatic nerve of rats (tibial and common peroneal nerves) leaving the sural nerve intact. Continuous intrathe-cal administration of propentofylline, a glial modulating agent, 1 d before and 5 d after operation, was performed to disrupt spinal cord glia function. The vehicle was intrathecally administrated as control. The paw withdrawal threshold to mechanical stimulation (paw withdrawal mechaical threshold PWMT), body mass and motor function were determined pre- and post-surgery. Results: It produced a prolonged mechanical allodynia in the medial and lateral part of the ipsilateral hind paw in SNL models. The treatment with propentofylline significantly prevented the development of mechanical allodynia located in either medial or lateral plantar surface. Rats in two groups showed normal motor function and body weight increase. Conclusion: SNI model can be applied as a useful method with little variance in searching the mechanism of neuropathic pain. These study suggest that spinal glia activation may contribute to mechanical allodynia induced by SNI.
基金supported in part by grants from National Nat-ural Science Foundation of China (82200726 and U23A20451)Key Program of the National Natural Science Foundation of China (81930016)National Key Research and Development Program of China (2021YFA1100500)。
文摘Tumor recurrence, the Gordian knot of liver transplantation for malignancies, may be attributed to many parameters. The technique of the “classical” recipient hepatectomy is believed to be one of the potential reasons to cause tumor evasion because of the possible increase of circulating tumor cells, thus leading to an increased recurrent rate. On this background, the no-touch oncological recipient hepatectomy technique has been developed. A comprehensive review of the development and the key surgical steps of the no-touch recipient hepatectomy is presented. This technique might improve clinical outcomes, especially for those recipients who are at a high risk for tumor recurrence. Multicenter prospective studies should be set up to further validate the prognostic role of this technique in patients with liver cancer treated with liver transplantation.
文摘BACKGROUND Laparoscopic nephrectomy is a preferred surgical approach due to its minimally invasive nature and faster recovery times.However,effective management of postoperative pain remains a significant challenge.Several traditional methods,including opioid-based analgesia,are commonly used but are associated with side effects such as nausea,vomiting,sedation,and delayed recovery.In recent years,the erector spinae plane block(ESPB)has gained attention as an ultrasoundguided regional anesthesia technique offering promising results in various surgical procedures by reducing opioid requirements and enhancing patient comfort.AIM To evaluate the efficacy and safety of ESPB in comparison to conventional pain management strategies in patients undergoing laparoscopic nephrectomy.METHODS Following PRISMA guidelines,we searched PubMed,EMBASE,Web of Science,and the Cochrane Register for randomized controlled trials(RCTs)comparing ESPB with control for laparoscopic nephrectomy.The Cochrane Risk of Bias tool was employed for quality assessment.The primary outcome was total patient-controlled analgesia(PCA)consumption.Secondary outcomes included hospital discharge time and the incidence of postoperative nausea and vomiting.A random-effects meta-analysis was conducted to calculate pooled mean differences(MD)and odds ratios(OR)with 95%CIs.RESULTS Nine RCTs involving a total of 643 patients(ESPB group=320;control group=323)were included in the analysis.ESPB significantly reduced PCA opioid consumption compared to controls(MD:-14.24,95%CI:-20.66 to-7.83,P<0.0001).Subgroup analysis showed reduced PCA use with ESPB vs morphine(MD:-8.78,95%CI:-15.34 to-2.22,P=0.009),and a non-significant effect compared to other analgesics(MD:-48.26,95%CI:-143.60 to 47.09).No statistically significant differences were observed in discharge time or the incidence of nausea and vomiting.CONCLUSION ESPB demonstrates the potential of reducing PCA in laparoscopic nephrectomy patients;however,its impact on secondary outcomes remains inconclusive.Large-scale RCTs are needed to confirm ESPB's benefits and explore long-term effects.
基金Supported by Fujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma,No.2020Y2014Fuzhou Health Technology Innovation Platform Construction Project,No.2019-S-wp2.
文摘BACKGROUND The volar approach with plate fixation is the gold standard for treating distal radius fractures,often requiring incision of the pronator quadratus(PQ)muscle.Preserving the PQ during surgery may facilitate early postoperative recovery.However,conventional minimally invasive plate osteosynthesis(MIPO)techniques frequently necessitate multiple(3-4)intraoperative fluoroscopic adjustments to achieve optimal plate positioning,which can inadvertently damage the PQ muscle.Based on our clinical observations,we developed a novel 3-point positioning technique to minimize PQ injury while ensuring accurate plate placement.Preliminary results demonstrate promising early clinical outcomes.AIM To retrospectively analyze distal radius fractures treated using the 3-point positioning-assisted MIPO technique with preservation of the PQ.METHODS The 3-point positioning technique was applied:The Kirschner wire was inserted after fluoroscopy and was correctly adjusted the position of the plate above the PQ.With the aid of Kirschner wires positioning the PQ stripping was performed only once,and the plate then placed in a correct and satisfactory position.Operation time,incision length,wrist pain score,upper extremity function disabilities of the arm,shoulder and hand(DASH)score,wrist Gartland-Werley score,wrist grip strength,and range of motion were among the quantitative variables recorded.Qualitative variables including AO fracture classification,intraoperative and postoperative complications were evaluated.RESULTS At a mean follow-up of 6.9±0.8 months,the mean scar length was 25.4±1.5 mm,the pain score was 0.7±0.6,the DASH score for the upper limb was 4.7±1.3,and the Gartland-Werley score for wrist function was 4.1±1.1 at the last follow-up.Mean flexion was 97.3%,extension was 97.0%,pronation was 98.9%,supination was 98.9%,and grip strength was 86.6%compared to contralateral values.No unfavorable intraoperative or postoperative complications occurred.CONCLUSION The 3-point positioning technique may reduce the damage to the PQ muscle and is a safe and effective method for MIPO for distal radius fractures.
文摘On July 17,2024,Chinese electric vehicle manufacturer GAC International opened a smart factory in Rayong Province,Thailand.The next day,then Prime Minister of Thailand Saita Thawaixin met with a delegation led by Zeng Qinghong,chairman of GAC Group.He encouraged GAC to purchase various spare parts in Thailand to enhance Thailand’s position in the global electric vehicle industry supply chain.“Thailand has a favorable business environment,”Zeng responded.“As the location of GAC’s first wholly-owned overseas facility,it was our premier choice.”
文摘Dear Editor,Primary bladder neck obstruction(PBNO)affects approximately 28%–54%of men[1].Its etiology remains unclear.Symptoms of PBNO present as voiding(e.g.,decreased force of stream,hesitancy,intermittent stream,and incomplete emptying),storage(e.g.,frequency,urgency,urge incontinence,and nocturia),or a combination of both[2].Untreated PBNO can lead to bladder dysfunction,bladder diverticula,hydronephrosis,and impaired renal function[3].
文摘Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracoscopic surgery (VATS) was carried out under general anesthesia. A double lumen endobronchial tube was intubated into trachea. One lung ventilation of the healthy side was done during operation. An incision of 8–10 cm long was made along the 4th or 5th intercostals. The lobectomy could be performed under VATS. Radionuclide colloid 32P was injected locally into the area where surgical cleaning of lymph node around was considered to be unsatisfactory or desection of the tumor was not completed. Results: The operation with VEMAST was successful in 29 patients. A conventional lobectomy by thoracotomy had to be done due to unusual bleeding from the pulmonary artery involved during VEMAST in one case and the procedure was interrupted because the pulmonary artery cloud not be separated from the tumor in another patient. There was no dead case or the patient who had any severe complication or adverse response to the radiant. Conclusion: Radionuclide therapy was performed to the treatment of stage II lung cancer with VEMAST in case that surgical resection was considered not to be satisfactory. Minithoractomy assisted with VATS lobectomy and radionuclide colloid 32P therapy is a safe and e?ective technique for some selected stage II lung cancer.
基金co-supported by the General Armament Department Pre-research Foundation of China (Nos. 51304010206, 51327 020105)
文摘Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost （LCC）. With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the （s-1, s） and （R, Q） inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets：one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model＇s correctness, method＇s validity as well as optimization project＇s rationality are proved to a certain extent.
基金supported by the National Natural Science Foundation of China(6110413261304148)
文摘Level of repair analysis（LORA） is an important method of maintenance decision for establishing systems of operation and maintenance in the equipment development period. Currently, the research on equipment of repair level focuses on economic analysis models which are used to optimize costs and rarely considers the maintenance time required by the implementation of the maintenance program. In fact, as to the system requiring high mission complete success, the maintenance time is an important factor which has a great influence on the availability of equipment systems. Considering the relationship between the maintenance time and the spares stocks level, it is obvious that there are contradictions between the maintenance time and the cost. In order to balance these two factors, it is necessary to build an optimization LORA model. To this end, the maintenance time representing performance characteristic is introduced, and on the basis of spares stocks which is traditionally regarded as a decision variable, a decision variable of repair level is added, and a multi-echelon multiindenture（MEMI） optimization LORA model is built which takes the best cost-effectiveness ratio as the criterion, the expected number of backorder（EBO） as the objective function and the cost as the constraint. Besides, the paper designs a convex programming algorithm of multi-variable for the optimization model, provides solutions to the non-convex objective function and methods for improving the efficiency of the algorithm. The method provided in this paper is proved to be credible and effective according to the numerical example and the simulation result.
文摘The gold standard for curative treatment of locally advanced rectal cancer involves radical resection with a total mesorectal excision(TME). TME is the most effective treatment strategy to reduce local recurrence and improve survival outcomes regardless of the surgical platform used. However, there are associated morbidities, functional consequences, and quality of life(QoL) issues associated with TME; these risks must be considered during the modern-day multidisciplinary treatment for rectal cancer. This has led to the development of new surgical techniques to improve patient, oncologic, and QoL outcomes. In this work, we review the evolution of TME to the transanal total mesorectal excision(TaTME) through more traditional minimally invasive platforms. The review the development, safety and feasibility, proposed benefits and risks of the procedure, implementation and education models, and future direction for research and implementation of the TaTME in colorectal surgery. While satisfactory short-term results have been reported, the procedure is in its infancy, and long term outcomes and definitive results from controlled trials are pending.As evidence for safety and feasibility accumulates,structured training programs to standardize teaching,training, and safe expansion will aid the safe spread of the TaTME.
