Objective:To analyze the safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma.Methods:PubMed,CNKI,VIP and Wanfang databases were searched to collect randomised controlled trials of PD-1 inhibi-tors in treatment of advanced melanoma.The search time was from the establishment of the database to May 1,2022.Two reviewers independently screened the literature,extracted data,and assessed risk of bias of included studies.Meta-analysis was performed using RevMan5.4 and STATA16 software.Results:A total of 7 studies were included.Meta-analysis results show that:①Safety:Compared with chemotherapy,PD-1 inhibitor treatment had fewer adverse events,especially in the blood system;compared with ipilimumab alone,PD-1 inhibitor combined with ipilimumab had more adverse events,especially liver function indicators;there was no signifi-cant difference in the incidence of total adverse events between PD-1 inhibitor monotherapy and ipilimumab monotherapy.②Efficacy:The PFS,OS and ORR of PD-1 inhibitor versus chemotherapy or ipilimumab were HR=0.54,95%CI(0.45,0.62),P<0.05,HR= 0.69,95%CI(0.58,0.80),P=0.03 and OR=3.16,95%CI(2.59,3.86),P<0.05,respectively.Conclusion:PD-1 inhibitors have good efficacy in treatment of advanced melanoma,while different combination methods and different control treatments may have different efficacy.Limited by the quantity and quality of included studies,more research evidence is needed to support this.

Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.

[摘 要] 目的：系统评价基于PD-1/PD-L1抑制剂的免疫联合治疗（以下称“免疫联合治疗”）对比舒尼替尼治疗晚期肾细胞癌（RCC）的安全性和有效性。方法：检索PubMed、Embase、Cochrane Library及中国知网（CNKI）数据库，收集国内外公开发表的免疫联合治疗对比舒尼替尼应用于晚期RCC的随机对照试验（RCT），检索时间均为自建库时间至2022年10月。由两名研究者独立评价纳入研究的质量、提取资料并交叉核对，采用StataMP16.0软件进行Meta分析。结果：共纳入6项RCT，Meta分析结果显示，（1）有效性：与舒尼替尼相比，免疫联合治疗显著提高了晚期RCC患者的总生存期[OS，HR=0.74，95% CI （0.67，0.80），P<0.01]和无进展生存期[PFS，HR=0.66，95% CI （0.51，0.81），P<0.01]；（2）安全性：两治疗组均有较高的不良反应（AE）发生率，差异无统计学意义。但免疫联合治疗组发生皮肤及内分泌系统AE显著高于舒尼替尼治疗组，而血液系统相关AE则明显低于舒尼替尼治疗组；（3）以1%为临界点，免疫联合治疗组的RCC患者，无论是PD-L1阳性或阴性的，其OS和PFS均高于舒尼替尼组。结论：免疫联合治疗可显著延长晚期RCC患者的OS和PFS，但不同系统发生AE有差异，且RCC患者PD-L1表达状态（1%为临界点）并不影响免疫联合治疗的获益。

OBJECTIVE: To compare the effects of different materials for partial sciatic nerve ligation on glial cell activation in the spinal cord in a rat model of chronic constriction injury (CCI). METHODS: SD rats were randomly divided into the sham group (=15), silk suture CCI group (=15) and chromic catgut CCI group (=14). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of the rats were detected at 3, 7, 11 and 15 days after the operation. The changes in the sciatic nerve, the activation of spinal cord glial cells and the expression of inflammatory factors were observed using Western blotting and RT-PCR. RESULTS: At 3 to 15 days after the surgery, MWT and TWL of the rats were significantly lower in silk suture group and chromic catgut group than in the control group ( < 0.05), and was significantly lower in chromic catgut group than in the silk suture group ( < 0.05) at 3 days after the surgery. The results of sciatic nerve myelin staining showed that the sciatic nerve was damaged and demyelinated in both the ligation groups. The expressions of CD11b, GFAP, IL-1β and TNF-α in the two ligation groups were similar and all significantly higher than those in the control group ( < 0.05). IL-6 mRNA level was significantly higher in chromic catgut group than in the silk suture group ( < 0.05). CONCLUSIONS The CCI models established by partial sciatic nerve ligation with silk suture and chromic catgut all show glial activation, and the inflammatory response is stronger in chromic catgut group.
Animals ; Constriction ; Neuroglia ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; Spinal Cord

Objective To evaluate the efficacy of ultrasound guided transversus abdominis plane block for elderly herpetic neuralgia located in anterior abdominal wall.Methods A total of 112 elderly patients aged 65-75 years with less than 30 days of herpes zoster neuralgia located in anterior abdominal wall were enrolled for receiving a treatment of transversus abdominis plane block.Patients were randomly allocated into two groups:the control group (n =56) taking gabapentin and celebrex,and the observation group (n =56)receiving transversus abdominis plane block (three times per week for two weeks) as add on therapy to gabapentin and celebrex.Morphine 10 mg was ready for oral application in breakthrough pain.Pain was evaluated by McGill scores assessed by short-form of Mcgill pain questionnaire(SF-M PQ)and visual analogue scale(VAS)before(T0)and after 1 (T1)and 2 weeks(T2)of transversus abdominis plane block,and 1 (T3)and 8(T4)weeks after end of the treatment.Pain relief(PAR)was calculated by the formula:PAR=(VAS score before block-VAS score after block)/ VAS score before block × 100％.The morphine consumption and sleep quality were observed during the treatment and 1 week after treatment.Analgesic efficacy was graded 8 weeks after end of treatment.The effective rate and good response rate were calculated.Incidences of complications were recorded.Results There was no significant difference in the VAS score between the two groups before treatment(t =0.419,P ＞0.05),while VAS scores after treatment were lower in the observation group than in the control group(t =17.925,19.662,12.580 and 13.987,respectively,P＜0.05).Before treatment,there was no significant difference in the total score of McGill between the two groups(t =0.544,P＞0.05).After treatment,the total scores of McGill were lower in the observation group than in the control group(t =18.612,20.135,13.213 and 12.356,respectively,P ＜0.05).The pre-therapy scores of sleep quality after treatment were decreased in the observation group as compared with the control group(t =7.798,9.545,10.335 and 16.318,respectively,P ＜0.05).Before treatment and at different time points of T1,T2,T3,T4,the morphine consumptions were not significant different between two groups(t =1.939,P＞0.05).While after treatment,the morphine consumptions were decreased in the observation group versus in the control group(t =22.341,16.758,17.827,15.541 respectively,P ＜0.05).No punctures of abdominal cavity,chest cavity,internal organs or blood vessels by mistake occurred.Conclusions Ultrasound-guided transversus abdominis plane block is effective and has less adverse reactions in treating herpetic neuralgia located in anterior abdominal wall.

OBJECTIVE:To systematically evaluate therapeutic efficacy and safety of Toutongning combined with flunarizine vs. flunarizine in the treatment of migraine,and to provide evidence-based reference in clinic. METHODS:Retrieved from PubMed,Cochrane library,Embase,Chinese Journal Full-text Database,Chinese Sci-tech Periodicals Database,Wanfang database and CBM,randomized controlled trials(RCTs)about therapeutic efficacy(total response rate,VAS score,blood potassium and blood magnesium concentration,CGRP level)and safety(the incidence of ADR)of Toutongning combined with flunarizine(trial group)vs. flunarizine in the treatment of migraine(control group)were collected. Meta-analysis of included trials meet inclusion criteria was conducted by using Stata 14.0 software,and trial sequential analysis(TSA)was conducted by using TSA 0.9 software after data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale. RESULTS:Totally 16 RCTs were included,involving 1 726 patients. Results of Meta-analysis showed that total response rate [RR=1.21,95%CI(1.16, 1.26),P<0.05],the decrease of VAS score [WMD=-1.04,95%CI(-1.42,-0.66),P<0.001],the decrease of blood potassium [WMD=-2.05,95%CI(-0.32,-0.18),P<0.001],the increase of blood magnesium [WMD=0.09,95%CI(0.04,0.14),P<0.001] and the decrease of CGRP [WMD=-2.22,95%CI(-3.25,-1.18),P<0.001] in trial group were better than control group,with statistical significance. The incidence of ADR in trial group was 2.27% in trial group and 2.89% in control group, without statistical significance(P>0.05). TSA showed that there were extract evidences for total response rate of Toutongning combined with flunarizine in the treatment migraine. CONCLUSIONS:Therapeutic efficacy of Toutongning combined with flunarizine is better than flunarizine in the treatment of migraine,and the ADR is not increased.

Objective To compare outcomes of laparoscopic radical prostatectomy (LRP) and open radical prostatectomy (ORP) performed in our hospital.Methods A non-randomized,retrospective comparative study was performed to analysis 302 prostate cancer patients from January 2011 to June 2014.One hundred and ten patients underwent LRP and 192 underwent ORP.There were no significant differences between the LRP and ORP groups with respect to patient age,body mass index,PSA level,Gleason Score,clinical T stage and transrectal ultrasonography prostate volume (P ＞ 0.05).The operating time,estimated blood loss,catheter retaining time,hospital stay time,positive surgical margin rate and urinary control rate were compared between the 2 groups.Results The median operative time of the ORP group and the LRP group was 95 min and 120 min,the difference between groups was significant (P ＜ 0.01).The median duration of hospitalization of the 2 groups was 9 d and 6 d,the difference between groups was significant (P＜0.01).ORP group and LRP group's estimated blood loss was 350 ml and 250 ml.Days of tube drainage were 3 d in both groups.Days of urinary catheterization drainage after surgery were 16 d and 15 d,respectively.Positive margin rate was 10.4％ and 12.7％.Urinary continence recovery rates at 3 month were 80.2％ and 70.8％.Urinary continence recovery rates at 6 month were 85.9％ and 87.3％.No significant difference was observed in the above index (P ＞ 0.05).Conclusions Compared with ORP,LRP has shorter hospital stay time and longer operating time.Both LRP and ORP have good outcomes in oncological control and function rehabilitation.Both of them are important procedures to treat localized prostate cancer.

BACKGROUNDEarly detection of pulmonary tuberculosis (PTB) is a big challenge in smear negative and sputum scarce patients in China. Simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis (MTB) complex (SAT-TB assay) is a novel molecular technique established in our hospital. This method has a high sensitivity and specificity in the lab. In this study, the clinical diagnostic performance of this method in smear-negative or sputum-scarce PTB suspects was investigated and evaluated.

METHODSTwo hundred smear negative and 80 sputum-scarce patients were recruited in this study. Samples that included sputum or bronchial washing fluid were collected and sent for both bacteria culture and SAT-TB assay. Diagnosis for these patients was based on the comprehensive evaluation of chestX- ray/CT study, histology examination, lab results, and treatment response. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each diagnostic test were investigated and calculated using confirmed tuberculosis (TB) and non-TB cases. The time required for detection of MTB was also measured for each method.

RESULTSNinety-two patients (33%) were diagnosed as definitive TB, 112 patients (40%) were probable PTB, and 76 (27%) were non-TB. The sensitivity, specificity, PPV, and NPV of SAT-TB in smear-negative PTB suspects were 93% (95% CI, 84%-98%), 98% (95% CI, 90%-100%), 98% (95% CI, 91%-100%), and 93% (95% CI, 83%-98%). In sputum scarce PTB suspects, the sensitivity, specificity, PPV, and NPV of the SAT-TB assay on bronchial washing fluids were 90% (95% CI, 74%-98%), 100% (95% CI, 85%-100%), 100% (95% CI, 88%-100%), and 88% (95% CI, 69%-97%). The accuracy of the SAT-TB assay is consistent with the bacteria culture assay. The median time required for detecting MTB in the SAT-TB assay was 0.5 day, which was much faster than bacteria culture (28 days).

CONCLUSIONSThe SAT-TB assay is a fast and accurate method for the detection of MTB. It can be widely applied in the clinic and be an asset in early detection and management of PTB suspects, especially in those patients who are smear negative or sputum scarce.

Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; pathogenicity ; Nucleic Acid Amplification Techniques ; methods ; Sputum ; microbiology ; Tuberculosis, Pulmonary ; diagnosis ; Young Adult

Objective To evaluate the hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma.Methods Forty-four male patients and 18 female patients were included in this study.They were all with metastatic renal cell carcinoma and received sunitinib treatment at the dose of 50 mg daily in repeated 6 weeks cycle (4 weeks on and 2 weeks off).Toxicity was assessed every cycle with tumor assessments every 2 cycles via CT or PET-CT.Results Fifty patients (80.6％) had experienced treatment-related hematotoxicity,including leucocytopenia,anemia and thrombocytopenia.Severe hematological adverse events ( grade 3 -4 ) occured in 18 patients ( 29.0％ ) and slight events ( grade 1 - 2 ) in others (51.6％).Most of the hematological adverse events were manageable and reversible and treatment-changes (dose reduction,interruption) were necessary in severe cases.Almost half of the dose reduction (9/21,42.9％ ) were owing to hematotoxicity.Conclusions Sunitinib of 50 mg dose on schedule 4/2 is effective and well-tolerated in advanced renal carcinoma patients.Hematological adverse events are frequent in Chinese patients and can be controlled well.

Objective To evaluate ultrasound-guided posterior approach to intercostal block for herpetic neuralgia. Methods Forty-eight patients with herpetic neuralgia after appearance of rashes on the back of chest (the coursc ＜ 30 days) aged 56-84 yr received intercostal block performed via posterior approach under the guidance of ultrasound with a mixture of 0.75% ropivacaine, glucocorticoid and methylene blue. Pain was assessed with visual analogue scale (VAS) before block and at 1, 2, 4 and 8 weeks after block. Pain relief (PAR) was cal-culated (PAR= (VAS score before block- VAS score after block) ÷ VAS score before block × 100%). Results No patient developed dyspnea and pneumothorax. VAS scores were reduced significantly, quality of life was improved and PAR increased at 1, 2, 4 ancl 8 weeks after block ( P ＜ 0.05 or 0.01). Concluslon Ultracound-guided posterior approach to intercostal block is safe and effective for the treatment of herpetic neuralgia.