Background Carbachol solution (0.01％) is an agonist of M cholinoceptor and skeletal muscle N cholinoceptor,and it is used to play miotic effect and open peripheral iridectomic hole during the surgery of implantable collamer lens (ICL) implantation in order to lower intraocular pressure (IOP).However,the anterior chamber injection of 0.01％ carbachol solution often causes relevant complications,while whether lower dose of carbachol solution is effective and safe is unclear.Objective This study was to compare the effectiveness and safety between 0.01％ carbachol solution and 0.005％ carbachol solution after anterior chamber injection during the ICL implantation.Methods One hundred and fifty-two eyes of 76 cataract patients were included in Daping Hospital of Third Military Medical University from September 2014 to September 2015.ICL implantation and periphery iridectomy were carried out on both eyes of the patients and the 0.01％ carbachol solution was injected into the anterior chamber during the surgery of the right eyes and 0.01％ carbachol solution was used in the left eyes.The operation duration and IOP at postoperative 2 hours and systemic choline-like reaction were compared between 0.01％ carbachol solution group and 0.005％ carbachol solution group.Results The mean operation duration was (11.86± 2.39) minutes and (11.22 ± 1.85) minutes in the 0.01％ carbachol group and 0.005％ carbachol group,without significant difference between two groups (t =1.851,P =0.066).IOP was (15.76 ± 2.18) mmHg and (13.58 ±2.24)mmHg in the 0.01％ carbachol group before and after surgery,and those in the 0.005％ carbachol group was (15.70±2.35)mmHg and (13.12±2.17)mmHg,there was no significant difference in the IOP between the two concentrations of carbachol (Fsroup =0.986,P=O.322).The IOP at postoperative 2 hours was lower than that before operation,the difference was statistically significant(Ftime =97.339,P =0.000).There was no interaction between drug concentration and time (Fcorrelation =0.772,P =0.381).The incidences of complications,such as dizziness,nausea and vomiting,were lower in the 0.005％ carbachol group than those in the 0.01％ carbachol group (x2 =13.01,5.16,4.03,all at P＜0.05).Conclusions Carbachol solution (0.005％) can play intraoperative miosis effect and maintain effective operation duration in ICL implantation.In addition,the application of 0.005％ carbachol solution is quite safe in both intraoperation and postoperation.

Objective This study was to explore the expression and significance of HMA2 in bladder cancer , analyze its correlations to clinicopathologic and recurrence of bladder cancer. Methods The expression of HMGA2 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues was detected by immunohistochemtry, its correlations to clinicopathologic features was analyzed. Results There was no expression of HMGA2 protein in normal bladder tissues,while the expression level of HMGA2 protein was getting higher with the increase of tumor pathology grade and stage. The positive rate of HMGA2 protein was 21.3% in G1 bladder cancer, 60. 3% in G2 bladder cancer, 82.1% in G3 bladder cancer, its difference is significant (P＜0. 001). It was significantly lower in non-muscle invasive bladder cancer than in muscle invasive bladder cancer (43.3% vs 72. 7%, P=0. 003). The patients were followed up for 2～95 months, patients of recurrence was 64,HMGA2 protein expression was significantly higher in patients with recurrence than with non-recurrence (54.7% vs 25.0%, P=0. 007). Conclusions The expression of HMGA2 protein was highly in bladder cancer, the positive rate of HMGA2 protein expression was related with classification,TMN stage and recurrence, but not with sex, age, tumor number (P＞0. 05). The detection of the expression of HMGA2 protein is in favor of diagnosis and prognostic evaluation of bladder cancer.

Objective· To evaluate the safety of neoadjuvant therapy which was constituted by docetaxel based systemic chemotherapy and maximal androgen blockage for patients with locally advanced prostate cancer and to summarize the related adverse events and clinical managements.Methods· From June 2015 to February 2017,the clinical data of 55 patients undergoing neoadjuvant chemotherapy combined with complete androgen deprivation were retrospectively reviewed.The patients were given docetaxel and prednisone as DP regimen every 3 weeks and LHRH analogues with bicalutamide as maximal androgen deprivation for a total of 4 cycles.All treatment-related adverse events were observed and then recorded.Results· Two cases with liver function impairment after 2 cycles of treatment were withdrawn from the study.No severe allergic reactions occurred during neoadjuvant therapy.The most common adverse events were hematologic toxicity,while 23.6％ of patients had grade Ⅲ-Ⅳ neutropenia,and about 12.7％ had anemia.Due to a relatively short course of treatment,the skin or mucous damage,peripheral neurotoxicity and fluid retention were rare.However,hot flash,male breast development as well as erectile dysfunction were very frequently observed due to maximal androgen deprivation.The majority of these adverse events were relieved by symptomatic and supportive treatment.Conclusion · After strict selection,4 cycles of neoadjuvant chemotherapy combined with total androgen blockade could be well tolerated by the patients with high-risk locally advanced prostate cancer.Even though the adverse events were controllable,they still need to be closely monitored during treatment in order to reduce the incidence.In addition,the very low testosterone level associated endocrinal metabolic disorders caused by complete androgen deprivation were also of great concern.

Objective To investigate genotyps of Treponema pallidum (Tp) in several cities in Guangxi province. Methods A total of 300 patients with suspected early syphilis were enrolled from STD clinics in Guangxi between January 2012 and July 2016, and tissue fluid samples were collected from skin lesions. Silver staining was performed to detect Tp, and PCR to amplify the Tp polA gene for the diagnosis of early syphilis. Positive samples were subjected to PCR amplification of a 60-bp tandem repeat region within the arp gene, restriction fragment length polymorphism(RFLP)analysis of the tpr Ⅱgene after digestion with Mse Ⅰ enzyme and tp0548 genotyping. Results Finally, 215 patients were diagnosed with early syphilis, including 210(97.7%)patients positive for PCR and 105(48.8%)patients positive for silver staining, and the positive rate significantly differed between the two methods (χ2 = 103.01, P < 0.05). Among the PCR-positive samples, 190 could be genotyped by analysis of three target genes, and 17 genotypes were identified. The genotype 14d/f was predominant (45.3%, 86/190), followed by 15d/f (13.7%, 26/190), 16d/f(11.6%, 22/190), 17d/f(7.4%, 14/190), 13d/f(6.8%, 13/190), 10d/f(4.2%, 8/190), 18d/f(1.6%, 3/190), 16a/f(1.6%, 3/190), 5d/f(1.1%, 2/190), 7d/f(1.1%, 2/190), 12d/f(1.1%, 2/190), 16d/e(1.1%, 2/190), 14a/f(1.1%, 2/190), 9h/c(1.1%, 2/190), 15l/f(0.5%, 1/190), 25a/e(0.5%, 1/190), 15i/f(0.5%, 1/190). Conclusion Tp genotypes are diversified in patients with early syphilis in Guangxi, and the genotype 14 d/f is predominant.

Objective:To assess the susceptibility of gonococcal clinical isolates to gentamicin in Guangxi region, China, and to analyze the correlation between the minimum inhibitory concentration (MIC) of gentamicin and MICs of 7 other antibiotics.Methods:From December 2020 to December 2021, 584 gonococcal clinical isolates were collected from 37 medical institutions in 14 prefecture-level cities in Guangxi region. The susceptibility of gonococcal clinical isolates to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, tetracycline, ciprofloxacin and gentamicin was determined by using an agar dilution method. The MIC values of antibiotics were logarithmically transformed with base 2, and Spearman correlation analysis was carried out to evaluate the correlation between the MIC of gentamicin and MICs of the other 7 antibiotics.Results:The MIC of gentamicin ranged from 1 to 16 mg/L, and the MIC50 and MIC90 values were 4 and 8 mg/L, respectively; 361 strains (61.8%) were fully sensitive to gentamicin with the MIC ≤ 4 mg/L, 223 strains (38.2%) moderately sensitive with the MIC ranging from 8 to 16 mg/L, and no gentamicin-resistant strains were found. The number of strains resistant to azithromycin, penicillin, tetracycline and ciprofloxacin was 136 (23.3%), 415 (71.1%), 339 (58.0%) and 574 (98.3%) respectively, the number of lowly sensitive strains to ceftriaxone and cefixime was 17 (2.9%) and 6 (1.0%) respectively, and no spectinomycin-resistant strains were found. Spearman correlation analysis showed that the MIC of gentamicin was weakly correlated with the MICs of azithromycin, spectinomycin, penicillin, tetracycline, and ciprofloxacin (all P < 0.05), but was uncorrelated with the MICs of ceftriaxone and cefixime (both P > 0.05) . Conclusion:All gonococcal clinical isolates tested in this study showed a certain degree of susceptibility to gentamicin, and cross-resistance between gentamicin and other antibiotics was less likely to occur.

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg^-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.