OBJECTIVE To investigate the protective effect and mechanism of saikosaponin C （SSC） on acute liver injury （ALI） in mice induced by carbon tetrachloride （CCl4） based on serum metabolomics. METHODS Forty mice were divided into blank group （water）， model group （water）， positive control drug group （Biphenyl diester drop pills， 150 mg/kg）， and SSC low- and high-dose groups （2.5， 10 mg/kg） using the random number table method， with 8 mice in each group. They were given water/ relevant drugs， once a day， for 7 consecutive days. One hour after the last administration， all mice were intraperitoneally injected with 0.2% CCl4 olive oil to induce ALI model， except for the blank group. After 17 hours of the modeling， the liver index of mice was calculated. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in serum of mice were detected. The histopathological changes of liver tissue were observed. Meanwhile， the serum metabolomics of mice were analyzed by liquid chromatography-mass spectrometry. RESULTS Compared with the blank group， the levels of liver index， ALT， AST， LDH， TNF-α， IL-6， and IL-1β in the model group were significantly increased （P＜0.01）. Hepatocytes were edema， vacuolar degeneration， more necrosis， and a large number of inflammatory cells were infiltrated. Compared with the model group， liver index and serum index levels of mice were significantly decreased （P＜0.05 or P＜0.01）， accompanied by marked improvement in histopathological damage to the liver tissue. The metabolomics results showed that compared with the model group， there were 63 up-regulated and 256 down-regulated differential metabolites in the serum of mice in the SSC high-dose group， including prostaglandin B2， 20-hydroxy-leukotriene B4， 5- hydroxy-L-tryptophan， 7α -hydroxycholesterol， etc.； these metabolites were primarily involved in metabolic pathways such as arachidonic acid metabolism， 5-hydroxytryptamine synapse， primary bile acid biosynthesis. CONCLUSIONS SSC exerts a protective effect against CCl4-induced ALI by down-regulating the level of key metabolites such as prostaglandin B2 and 20-hydroxy-leukotriene B4， and then ruducing metabolic pathways such as arachidonic acid metabolism， 5- hydroxytryptamine synapse， and primary bile acid biosynthesis.

Objective To explore the effects of image registration using various regions of interest(ROI)on the setup error for nasopharyngeal carcinoma(NPC)patients who were immobilized individually.Methods Forty-three NPC patients who required radiotherapy were enrolled.The patients were immobilized with customized plastic foam and thermoplastic mask,and CBCT verification was performed once a week.In CBCT images,ROI was divided into the whole ROI(ROIPTV)and 7 local ROI containing different cervical structures(ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,ROIneck4,ROIneck5,ROIneck6,and ROIneck7),which were then used for registrations with localized CT image.The setup errors in superior-inferior(SI),left-right(LR),anterior-posterior(AP),Pitch,Roll,and Yaw directions were recorded.Results In SI direction,the setup errors within 0.3 cm accounted for 89.74%for ROIneck7,and more than 90%for the other ROI.The proportion of setup errors within 0.3 cm gradually increased with the neck upward in LR direction,and they were 76.78%,81.70%,85.26%,and above 90%for ROIneck7,ROIneck6,ROIneck5,and the other ROI,respectively.In AP direction,the proportions of setup errors within 0.3 cm were less than 90%,except for ROIatlantoaxial and ROIneck3.The setup errors of ROIsphenoid sinus,ROIatlantoaxial,ROIneck3,and ROIneck4 were significantly positively correlated with ROIPTV in SI direction,and the correlation coefficients(R)were 0.94,0.95,0.90,and 0.83,respectively.In LR direction,there were positive correlations between the setup errors of ROIatlantoaxial and ROIsphenoid sinus(R=0.95),ROIneck3 and ROIsphenoid sinus(R=0.91),ROIPTV and ROIneck3(R=0.91).The setup errors of ROIPTV in AP direction were positively correlated with ROIatlantoaxial vertebrae and ROIneck3(R=0.88,0.90).The margins of all ROIs ranged from 0.38 cm to 1.01 cm.The extension of ROIneck6 and ROIneck7 in AP direction exceeded 0.9 cm,and the extension of ROIneck7 reached 0.95 cm in SI direction.Conclusion ROIPTV and ROIsphenoid sinus,ROIatlantoaxial,ROIneck3 are significantly correlated in SI,LR,and AP directions.The setup error of nasopharyngeal carcinoma patients gradually increases with the neck down.The nasopharyngeal and cervical regions need to be expanded in segments when patients are immobilized individually.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.
Mice ; Animals ; Mice, Obese ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Network Pharmacology ; RNA, Ribosomal, 16S ; Diabetes Mellitus, Type 2/complications* ; Obesity/genetics* ; Body Weight ; Lipids ; Insulin ; Transcription Factors ; Dyslipidemias/genetics* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88％on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66％on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.