Objective To investigate the clinical efficacy of percutaneous nephrolithotomy with holmium laser(YAG laser lithotripsy)for the treatment of renal calculi.Methods Percutaneous puncture was performed under continuous epidural anesthesia,and then a pyeloscope(Wolf F8.5/11.5)was inserted and lithotripsy was carried out by using 200-?m holmium laser fiber(0.6-1.2 J/6-10 Hz).After the procedure,the pieces of the calculi were removed.After the operation,renal fistula was maintained for 3-5 d,urethral catheter was retained for 5-7 d,and double-J catheter was kept for 4-8 weeks.Results Stone removal was achieved with one-stage operation in 130 cases [mean operation time,60 minutes(40-150 minutes);and mean hospital stay,8.5 d(7-10 d)];with two-stage operation in 15 cases [mean hospital stay,14 d(12-16 d)];and with three-stage operation in 5 [mean hospital stay,17 d(15-20 d)].In all the 150 cases,by using single tract,stone-free rate reached 86.0%(129/150)after the first-stage operation,and final stone-free rate was 92.0%(138/150).None of the patients had severe complications after the operation.Conclusion Percutaneous nephrolithotomy by using holmium laser is minimally invasive,effective and safe for patients with renal calculi.

There exists a population of myeloid-origin cells that are associated with tumor immune escape in cancer patients,commonly termed as myeloid derived suppressor cells(MDSCs).M DSCs accumulate in the blood,lymph nodes,bone marrow,and inhibit both adptive and innate immunity.Different suppressive mechanisms are used by MDSCs to block tumor immunity.Reducing the numbers of MDSCs or inhibiting the suppressive pathway conducted by MDSCs will bring new highlight to biotherapy in tumor treatment.

Objective:To observe clinical therapeutic effects of method for supplementing Qi,activating blood circulation and resolving phlegm and effects on vascular endothelial function and blood coagulation system in senile patient of hyperlipemia.Methods:96 senile patients of hyperlipemia were randomly divided into a treatment group(n=56)and a control group(n=40).The patients of the treatment group were treated by oral administration of Danshen Jueming Granules and the control group by oral administration of Xuezhikang Capsules.Blood lipids,vascular endothelial function,blood coagulation system and safety were observed.Results:After treatment,the treatment group in decrease of plasma total cholesterol(TC)and low density lipoprotein-cholesterol(LDL-C)was superior to the control group(P

Objective: To separate and identify the exosomes derived from MCF-7 tumor cells,and observe their function on IL-2 induced lymphocyte proliferation.Methods:The exosomes were separated by serial centrifugation,concentration and density gradient centrifugation, and then identified by transmission electron microscope.The effects of exosomes on IL-2 induced proliferation were studied by MTT method.Results:Total 20 mL exosomes from 2×10~7 MCF-7 cells with concentration of protein were(1.84±0.01) g/L. The diameters of these purified bi-layer membrane exosomes were 55-70 nm, which were consistent with the internal vesicles in multi-vesicular endosomes.The result of MTT test showed that proliferation of donor peripheral blood lymphocytes was inhibited by tumor exosomes at a dose-dependent manner in response to IL-2.Conclusion:It is feasible to separate high-purity exosomes from tumor cell culture medium supernatant by serial centrifugation and concentrate method. These tumor derived exosomes have inhibitory effect on IL-2 induced proliferation.

The poor prognosis of hepatocellular carcinoma (HCC) is strongly associated with invasion and metastasis.Recently,the epithelial-mesenchymal transition (EMT) has been confirmed to be the cytological foundation of invasion and metastasis.Yet,the molecular mechanism of inducing and maintaining EMT has not been expounded completely.However,it has been demonstrated that transforming growth factor-β (TGF-β),phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT),nuclear factor-κB (NF-κB),Wnt/β-catenin signaling pathways play pivotal roles in the initiation and development of EMT.These signaling pathways can affect the prognosis of HCC by regulating EMT.From a drug development perspective,these signal pathways are potential and attractive targets for HCC treatment.

Objective: To investigate the expression of TSLP in human lung cancer tissue and the correla-tion between TSLP expression and number of regulatory T cells (Tregs). Methods: The expression of TSLP mRNA and protein was detected in different pathological lesions of the lung by Q-RT-PCR and immunohisto-chemistry. Immunohistochemistry was used to detect Foxp3+ Tregs. The correlation of TSLP with the number of Tregs was analyzed. Results: TSLP gene was expressed in tumor tissues (n=37), latero-tumor tissues (n=29) and non-tumor lung tissues (n=24), without statistical difference (P=0.148). TSLP protein was expressed in the cytoplasm and was observeed in 69.57% of tumor tissues, 13.33% of benign lesions and 30.00% of non-tumor lung tissues, with a significant difference (P<0.05). The expression of TSLP protein was correlated with tumor size (P=0.000) and lymph node metastasis (P=0.018). The number of Tregs in TSLP positive group was more than that in TSLP negative group (P<0.05). Conclusion: The expression of TSLP in lung tu-mor tissues is increased and is correlated with the number of Tregs, indicating that TSLP could induce Treg to play an important role in tumor immunotolerance.

OBJECTIVE:Exercise intervention is one of the main treatments for fibromyalgia,but there is no consistent conclusion on the choice of different exercise modalities.In this article,a network Meta-analysis was used to comprehensively and quantitatively evaluate the effects of different exercise modalities on fibromyalgia syndrome. METHODS:PubMed,EMbase,Scoups,The Cochrane Library,Web of Science,CNKI,WanFang Database,and China Biomedical Literature Database were searched for relevant literature,with a search timeframe from the establishment of each database to June 2023.The outcome indicators included five continuous variables,including fibromyalgia impact questionnaire-revised(FIQ)scores,visual analogue scale(VAS)scores,quality of life,quality of sleep,and depression.The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature.RevMan 5.4 software was used to perform effect sizes,subgroup analyses,and sensitivity analyses of the data.Stata 17 software was used to perform reticulation and network Meta-analysis of the data. RESULTS:A total of 13 articles with 14 randomized controlled trials were finally included.The overall methodological quality of the literature was high.The results of traditional Meta-analysis showed that,compared with the control group,exercise therapy significantly improved the FIQ score[standardized mean difference(SMD)=-0.67,95％confidence interval(CI):-0.83 to-0.50,P<0.01],VAS score(SMD=-0.72,95％CI:-0.90 to-0.54,P<0.01),quality of life(SMD=1.03,95％CI:0.45 to 1.61,P=0.000 5),sleep quality(SMD=-0.62,95％CI:-0.98 to-0.25,P=0.001),and depression(SMD=-0.63,95％CI:-1.09 to-0.18,P=0.007).Network Meta-analysis showed that the probability of optimal intervention effect of exercise modalities on FIQ scores was ranked as:mind-body exercise(86.5)>resistance exercise(70.5)>aerobic exercise(41.7);the probability of optimal intervention effect of exercise modalities on VAS scores was ranked as:resistance exercise(85.3)>mind-body exercise(74.3)>aerobic exercise(34.5). CONCLUSION:Exercise therapy significantly improves FIQ scores,VAS scores,quality of life,sleep quality,and depression in patients with fibromyalgia syndrome.Mind-body exercise and resistance exercise are the most effective exercise modalities to reduce FIQ scores and VAS scores in patients with fibromyalgia syndrome.

Objective:To investigate the function of breast cancer susceptibility gene variants in predicting breast cancer risk and guid-ing clinical treatment through DNA sequencing. Methods:This study involved 146 patients, 71 high-risk cases, and 55 healthy people, totaling 272 cases. The subjects were treated in Tianjin Medical University Cancer Institute and Hospital from November 2013 to July 2015. Genomic DNA was sequenced by a second generation sequencing platform. All exon areas of six common breast cancer suscepti-bility genes (BRCA1, BRCA2, PTEN, STK11, TP53, and RAP1) were sequenced through amplicon sequencing method. Meaningful vari-ants including single nucleotide variants (SNVs), insertion-deletions (InDels) and nonsense mutations were selected and statistical methods, such as t test andχ2 test, were used to analyze the statistical differences in incidence rates among three groups. Results:A total of 177 meaningful variants were confirmed, including 50 SNVs, 8 nonsense mutations, and 9 InDels. Among the variants, 31 were recorded in the Exome Aggregation Consortium (ExAC), 40 were noted in ClinVar database, and 21 were not encoded in the present da-tabase, which were defined as new variants in this study. Conversely, 57 variants (85.1%) were found in breast cancer patients and high-risk cases, and the incidence of axillary lymph node metastasis (P=0.010) and pathological stages (P=0.002) in mutation positive patients were both higher than mutation negative patients. Moreover, the percentage of family history of cancer (P=0.005) and triple negative breast cancer (P=0.009) were both higher in patients carrying pathogenic mutations than in nonpathogenic patients. Conclu-sion:Breast cancer susceptibility gene variants may not only be a tool used to predict the risk of getting breast cancer but also a mean-ingful guideline for the clinical treatment and prognosis evaluation.

Objective : To investigate the effect of miR-135a-5p on the expression levels of insulin-like factor 3 (INSL3) and testosterone in the testicular tissues of flutamide-induced cryptorchidism mouse． Methods : A model of flutamide-induced cryptorchidism in mouse was constructed，and the experiment was divided into normal control group，flutamide group，flutamide + miR-135a-5p knockdown group and flutamide + miR-135a-5p overexpression group. RT-qPCR was used to detect the expression levels of miR-135a-5p and INSL3 mRNA．Western blot was em- ployed to assess the protein expression level of INSL3．ELISA was performed to measure the expression level of tes- tosterone. Results : The expression levels of miR-135a-5p，INSL3 mRNA and protein and testosterone were significantly down-regulated in the testis of cryptorchid mice by flutamide (P＜0. 05) ．Knockdown of miR-135a-5p could downregulate the expression of INSL3 mRNA，INSL3 protein and testosterone (P ＜0. 01 ) ，while overexpression of miR-135a-5p had the opposite result． Conclusion miR-135a-5p decreased in flutamide-induced cryptorchidism mouse testicular tissues，and overexpression of miR-135a-5p could restore the expression levels of INSL3 and testosterone.

Objective: To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS). Methods: A panel of NGS was designed and sequencing was performed for DNA samples extracted from peripheral blood leukocytes of FNMTC patients and sporadic non-medullary thyroid carcinoma (SNMTC) cases, respectively, and gene mutations were screened. In addition, the clinicopathological characteristics, including tumor size, extension of surgery, lymph node metastasis and extra-thyroidal extension, were compared between patients with or without mutations. Results: In 63 NMTC samples, 45 mutations were detected on 13 genes. 37 germline mutations were detected in 47 FNMTC patients, while 8 germline mutations were detected in 16 SNMTC patients. In 8 FNMTC family lineages, the same mutations were carried by FNMTC patients from the same pedigree. The number of carriers of mutations was 29 in the 47 FNMTC patients and 6 in the 16 SNMTC patients, with a non-significant difference (P= 0.092). Among the FNMTC patients, there were 22 patients with central lymph node metastasis in the 29 mutation-positive patients, significantly more than 7 in the 16 mutation-negative cases (P= 0.031). As for the parentage, there were 3 patients with central lymph node involvement among the 7 patients of parent generation, while all the 9 patients of offspring generation had central lymph node metastasis (P=0.019). Conclusions This panel of NGS can be used to screen mutant susceptibility gene of FNMTC patients, and the findings may be helpful for early detection of FNMTC patients and predicting the disease risk to familial members of FNMTC patients.