Da Chaihutang from the Treatise on Febrile Disease （Shanghanlun） has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases， especially malignant tumors. By review of the articles published in the last 20 years， this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis， clinical research， and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system， release interior and exterior to expel pathogen， and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice， Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer， pancreatic cancer， intestinal cancer， gastric cancer， and gallbladder cancer. In addition， it can relieve common complications of digestive system malignant tumors， such as cancerous fever， malignant obstructive jaundice， and constipation. Moreover， it can alleviate the adverse reactions caused by Western medical treatment， such as post-embolization syndrome， side effects of chemotherapy， and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms， improve prognosis， and prolong survival of advanced patients and is safe and non-toxic， suitable for long-term use by tumor patients. Regarding the mechanism， Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells， reduce inflammation and inflammatory injury， and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research， aiming to provide reference for the application of this formula in treating digestive system tumors， the establishment of Chinese and Western medicine treatment schemes of tumors， and the research and development of anti-tumor drugs.

Objective To observe the effects of Bushen Zhuyun Prescription on regulating mitochondrial function and endometrial angiogenesis;To explore its mechanism of improving endometrial receptivity.Methods The mouse model of controlled ovarian hyperstimulation(COH)was established,and the mice were randomly divided into normal group,model group,and Bushen group,with 20 mice in each group.Bushen group received Bushen Zhuyun Prescription for gavage for 11 d,and the normal group and model group received normal saline for gavage.The number of embryo implantation was counted,the endometrial morphology was observed by HE staining,α-smooth muscle actin(α-SMA)expression was observed by immunofluorescence staining.Human endometrial microvascular endothelial cells(HEMECs)were cultured in vitro,they were divided into control group,VEGFA group,Bushen group and VEGFA + Bushen group,and were intervened with VEGFA and/or Bushen Zhuyun Prescription medicated serum.The activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ,the content of ATP,the expression of PCNA and Caspase-3 were detected.Results Animal experiment showed that,compared with the normal group,the number of embryo implantation in model group significantly decreased(P<0.05),α-SMA protein expression in endometrial tissue significantly decreased(P<0.05);compared with the model group,the number of embryo implantation in Bushen group significantly increased(P<0.05),α-SMA protein expression in endometrial tissue significantly increased(P<0.05).Cell experiment showed that,Bushen Zhuyun Prescription medicated serum could increase the activity of mitochondrial respiratory chain complexes Ⅰ-Ⅳ and ATP content in HEMECs,promote PCNA protein expression,and inhibit Caspase-3 protein expression(P<0.05,P<0.01).Conclusion Bushen Zhuyun Prescription can promote endometrial angiogenesis through improving mitochondrial function.

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

Hepatocellular carcinoma is the most common malignant tumor of the liver, and more than half of the patients are in the middle and late stage, seriously threatening the life and health of the Chinese people. Although surgical resection remains the only treatment option for liver cancer patients to achieve a cure, the low surgical resection rate and high postoperative recurrence rate greatly limit the survival benefits of patients. Recently, with the continuous successful development and clinical application of systemic new drugs, multi-mode therapy such as TKIs combined ICIs has sprung up, breaking the limitations of a single treatment model, and has become an important corner of "surgery-based comprehensive treatment" for liver cancer. Neoadjuvant therapy, adjuvant therapy and conversion therapy have gradually become the focus of new research, and their success is expected to further improve the survival prognosis of patients with liver cancer, but there are still many challenges. The author reviews the current first-line systematic treatment of liver cancer, and elaborates on the characteristics and advantages of its clinical application.

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 investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P＜0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P＜0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P＜0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.

Objective To construct recombinant human butyrylcholinesterase(rhBChE)knock-in goat fetal fibroblast cell lines(GFFs)by using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-mediated homology-directed repair mechanism for subsequent production of goat expressing rhBChE.Methods The efficient sgRNA sites targeting goat[3-casein(CSN2)gene were designed and screened,and the targeting efficiency of the sgRNA in goat mammary epithelial cells(GMECs)was confirmed by electro-transfection,flow sorting,and sequencing of PCR products.The red fluorescent reporter gene homology repair vector(P2A-mCherry)targeting the sgRNA was constructed,and then the integration and expression efficiency was detected by flow cytometry.The rhBChE homology repair vector(P2A-rhBChE)targeting the sgRNA of CSN2 gene was constructed in GFFs,the rhBChE positive cell clones were obtained via electro-transfection and flow sorting,and the rhBChE knock-in cell lines was identified by sequencing of PCR products.Results The sgRNA4 was identified as an efficient target of goat CSN2 gene,which could be also used for targeted integration of other genes.Three rhBChE knock-in cell lines were successfully constructed.Conclusion The rhBChE knock-in GFFs targeting goat CSN2 gene lays the foundation for the production of mammary bioreactors expressing rhBChE.

Objective:To analyze independent factors for treatment-requiring retinopathy of prematurity (TR-ROP) and establish a predictive nomogram model for TR-ROP.Method:A retrospective cohort study. A total of 6 998 preterm infants who were born at Guangdong Women's and Children's Hospital between January 1, 2012 and March 31, 2022 and were screened for retinopathy of prematurity (ROP) were included in the study. TR-ROP was defined as type 1 ROP and aggressive ROP; 22 independent factors including general information, maternal perinatal conditions, interventions and neonatal diseases related to ROP were collected. The infants were divided at the level at an 8:2 ratio according to clinical experience, with 5 598 in the training cohort and 1 400 in the validation cohort. t test was used for comparison of quantitative data and χ 2 test was used for comparison of counting data between groups. Multivariate logistic regression analysis was carried out for the indicators with differences in the univariate analysis. The visualized regression analysis results of R software were used to obtain the histogram. The accuracy of the nomogram was verified by C-index and receiver operating characteristic curve (ROC curve). Results:Among the 6 998 children tested, 4 069 were males and 2 920 were females. Gestational age was (33.69±3.19) weeks; birth weight was (2 090±660) g. There were 376 cases of TR-ROP (5.4%, 376/6 998). The results of multivariate logistic regression analysis showed that gestational age [odds ratio ( OR) =0.63, 95% confidence interval ( CI) 0.47-0.85, P=0.002], intrauterine distress ( OR=0.30, 95% CI 0.10-0.99, P=0.048), bronchopulmonary dysplasia ( OR=0.23, 95% CI 0.09-0.60, P=0.003), hypoxic-ischemic encephalopathy ( OR=5.40, 95% CI 1.45-20.10, P=0.012), blood transfusion history ( OR=4.05, 95% CI 1.50-10.95, P=0.006) were the independent influencing factors of TR-ROP. Based on this and combined with birth weight, a nomogram prediction model was established. The C-index of the training set and validation set were 0.940 and 0.885, respectively, and the area under ROC curve were 0.945 (95% CI 0.930-0.961) and 0.931 (95% CI 0.876-0.986), respectively. The sensitivity and specificity were 86.2%, 94.0% and 83.2%, 93.3%, respectively. Conclusions:Gestational age, intrauterine distress, bronchopulmonary dysplasia, hypoxic-ischemic encephalopathy and blood transfusion history are the independent factors influencing the occurrence of TR-ROP. The TR-ROP nomogram prediction model based on independent influencing factors has high sensitivity and specificity.

Humans ; Asthma/drug therapy* ; Biological Therapy