OBJECTIVE To systematically analyze the compatibility stability of commonly used intravenous antibiotics in the intensive care unit （ICU）， and to provide evidence-based support for rational clinical drug use. METHODS Medication data from the ICU of Hebei General Hospital between January and December 2024 were extracted from the Prescription Automatic Screening System. Commonly used intravenous antibiotics and other intravenous drugs in the ICU were selected through consultations with critical care and pharmacy experts in Hebei province， drug package inserts and compatibility information retrieved from Micromedex， Trissel’s Injectable Drug Handbook and PubMed. The physicochemical stability of drug combinations was analyzed. In addition， Cytoscape 3.10.2 software was used to construct a drug compatibility network for identifying high-risk drugs. RESULTS &CONCLUSIONS A total of 904 pairwise drug combinations involving 16 antibacterial agents and 65 intravenous drugs were collected. Among them， 549 combinations （60.7%） were compatible， 88 combinations （9.7%） were incompatible， 82 combinations （9.1%） had conflicting evidence， and 185 combinations （20.5%） lacked valid data support. High-risk combination drugs primarily involved Amphotericin B for injection， Ceftazidime for injection， Imipenem-cilastatin for injection， Ceftriaxone sodium for injection， Vancomycin hydrochloride for injection， etc. The main risk factors for drug-drug incompatibility included drug concentration， temperature， mixing rate， pH， and chemical structure. In clinical practice， drugs and diluents should be selected rationally based on specific compatibility data， and research and monitoring of drug compatibility should be further strengthened.

Objective To analyze the application value of uterine artery flow and cerebral placental rate(CPR)in diagnosing fetal growth restriction(FGR).Methods A total of 114 pregnant women with clinically diagnosed late-onset FGR who were hospitalized in Jiangxi Maternal and Child Health Hospital from January 2021 to June 2022 were assigned to study group,and 122 pregnant women with normal intrauterine development were assigned to control group.The blood flow parameters of uterine artery(UtA),umbilical artery(UA)and middle cerebral artery(MCA)in two groups were determined by ultrasound,and CPR in two groups was calculated.The blood flow difference and pregnancy outcome of two groups were compared.Receiver operating characteristic(ROC)curve was used to analyze the application value of UtA and CPR alone and combined in the clinical diagnosis of FGR.Results The UtA resistance index(RI)of pregnant women in study group was higher than that of control group,the fetal UA blood flow parameter was higher than that of control group,the MCA blood flow parameter and the CPR value were both lower than those of control group,the differences were statistically significant(P<0.05).The birth weight and 1min Apgar score of study group were lower than those of control group(P<0.001).In addition,the incidence of emergency cesarean section operation,premature delivery and neonates transferred to neonatal intensive care unit(NICU)due to various complications in study group were significantly higher than those in control group(P<0.05).ROC curve showed that in predicting FGR,the area under the curve(AUC)of UtA-RI was 0.82(95%CI:0.77-0.88).The predictive efficiency of CPR was 0.75(95%CI:0.69-0.81).The combination of UtA-RI and CPR parameters had the highest efficiency in predicting FGR,with an AUC of 0.92(95%CI:0.89-0.95).Conclusion CPR combined with UtA-RI monitoring has clinical application value for early detection of FGR,guiding intervention,and improving adverse perinatal outcomes.

Antidepressants are mainly used to treat mental illnesses. Traditional antidepressants mainly target monoamine neurotransmitters, but these drugs are slow to be effective and cannot meet clinical needs. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis and focus on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in clinical practice. This article mainly summarizes the research mechanisms and treatment programs of new antidepressants, and briefly reviews common rapid-acting antidepressants.

Objective: The molecular classification system of endometrial carcinoma (EC) in ‘The Cancer Genome Atlas’ is widely acknowledged for its prognostic utility. Subsequently, more simplified classification system that incorporate DNA polymerase epsilon (POLE) exonuclease domain mutations, mismatch repair deficiencies (MMRd), and abnormal p53 (P53abn) has also demonstrated its clinical utility. These classifications helped identifying a ‘POLE ultramutated’ (POLEmut) category of patients, most of whom show excellent prognoses despite having high-grade ECs. We aimed to investigate the clinicopathological and molecular characteristics of high-grade ECs with POLEmut. Methods: We investigated 414 patients with high-grade ECs (including endometrioid carcinomas grade 3, serous carcinomas, clear cell carcinomas, mixed carcinomas, undifferentiated and dedifferentiated carcinomas, and carcinosarcomas) by sequencing and immunohistochemical staining. Results: Forty-three tumors (10.4%) were classified as POLEmut, including 2 with new, possibly pathogenic POLE mutations at P286C and L424V. These patients had very good prognoses except for 1 with stage IV disease and residual tumor. Eleven patients in this group also had P53abn and 4 had MMRd; molecular analysis revealed that patients with synchronous POLE pathogenic mutation and other mutations had a POLEmut or MMRd phenotype; survival analysis found no difference in prognosis between these patient categories. The prognoses of patients in the POLEmut EC group were not significantly influenced by treatment or risk category. Conclusions Patients with high-grade EC exhibiting POLEmut have very good clinical outcomes, and should be identified urgently in daily work owing to their conflicting morphology. Our findings also provide guidance on subclassifying ECs with poor histological appearance.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Objective:To investigate the expression of B7 homolog 4 (B7-H4) and its clinical significance in endometrial cancer.Methods:A total of 833 patients with endometrial cancer admitted to Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from 2009 to 2019, were enrolled. The expression of B7-H4, mismatch repair (MMR), p53, programmed cell death ligand 1 (PD-L1) protein, and CD 8+ T lymphocyte density in endometrial cancer tissues were detected by the EnVision two-step method of immunohistochemical staining. First-generation sequencing (Sanger method) was used to determine molecular subtyping of endometrial cancer. The χ2 test was used to compare the differences in positive expression rate of B7-H4 protein in endometrial cancer tissues with different clinicopathological features and molecular subtyping, PD-L1 protein expression, and CD 8+ T lymphocyte density. Survival analyses [including recurrence-free survival (RFS) and disease-specific survival (DSS)] were performed for 664 patients with follow-up time≥3 months, with a median follow-up time of 31 months (range: 4-121 months), and the Cox proportional hazards regression model was used to analyze the relevant factors affecting the prognosis of patients with endometrial cancer. Results:(1) The median age of 833 patients was 58 years (range: 25-88 years); pathological type: 595 with endometrioid carcinoma, 238 with non-endometrioid carcinoma; surgical-pathological staging: 542 cases at stage Ⅰ, 38 cases at stage Ⅱ, 173 cases at stage Ⅲ, and 45 cases at stage Ⅳ. Molecular subtyping was performed in 590 patients, including 50 with POLE mutation, 163 with mismatch repair defect (MMR-d) type, 246 with nospecific molecular change (NSMP) type, and 131 with p53 mutation subtype. (2) B7-H4 protein was expressed with brownish-yellow stainind in the cell membrane and cytoplasm of endometrial carcinoma, and the positivity rate of B7-H4 protein was 71.5% (596/833). The positivity rates of B7-H4 protein among patients with different age, surgical-pathological stage, tumor grade, pathological type, depth of muscular invasion, presence or absence of lymphovascular space invasion, and molecular subtype were significantly different (all P<0.05). The positivity rates of B7-H4 protein among patients with different PD-L1 protein expression and CD 8+ T lymphocyte density were not significantly different ( P>0.05). The 5-year RFS (83.9%) and DSS (87.3%) of B7-H4 protein-positive patients had an increasing trend compared with the 5-year RFS (77.2%) and DSS (78.1%) of B7-H4 protein-negative patients, but there were not statistically significant differences ( P=0.053, P=0.083). (3) Univariate analysis showed that the 5-year RFS and DSS of patients with different age, tumor grade, surgical-pathological stage, pathological type, depth of muscular invasion, lymphovascular space invasion, and molecular subtype were significantly different (all P<0.01). There were no significant differences in 5-year RFS ( P=0.184, P=0.113) and DSS ( P=0.549, P=0.247) among patients with different CD 8+ T lymphocyte density and PD-L1 protein expression. Further analysis according to molecular subtype, the results of CD 8+ T lymphocyte density and PD-L1 protein expression showed that the 5-year RFS and DSS of B7-H4 protein-positive patients were higher than those of B7-H4 protein-negative patients with NSMP subtype, low density of CD 8+ T lymphocyte and PD-L1 protein-negative endometrial carcinoma (all P<0.05), however, there was no significant difference in 5-year DSS between B7-H4 protein-positive patients and B7-H4 protein-negative patients with PD-L1 protein-negative endometrial cancer ( P=0.060). Multivariate analysis showed that positive expression of B7-H4 protein was an independent factor for 5-year RFS ( HR=0.27, 95% CI: 0.09-0.78, P=0.016) and DSS ( HR=0.16, 95% CI: 0.05-0.58, P=0.005) in patients with NSMP subtype endometrial carcinoma. In patients with low-density CD 8+ T lymphocytes endometrial cancer, positive expression of B7-H4 protein was an independent factor for 5-year RFS ( HR=0.45, 95% CI: 0.26-0.80, P=0.006), but it was not an independent factor for 5-year DSS. In patients with PD-L1 protein-negative endometrial cancer, B7-H4 protein was not an independent factor for 5-year RFS. Conclusion:B7-H4 protein expressed highly in endometrial carcinoma tissues, and its high expression is closely related to clinicopathological features, molecular subtype of p53 mutant and NSMP, and the favorable prognosis of patients with low density of CD 8+ T lymphocyte immunophenotype endometrial carcinoma.

Objective To investigate the feasibility and safety of laparoscopic combined with choledochoscopy for choledocholithotomy and primary suture. Methods 82 patients who underwent laparoscopic combined with choledochoscopy for choledocholithotomy and primary suture from Hechi People's Hospital from June 2016 to August 2018 were enrolled as study objects. They were divided into study group and control group according to the different treatment methods of common bile duct incision. 40 patients in the study group underwent primary suture of the common bile duct and 42 patients in the control group underwent T-tube drainage. The surgical outcomes and complications of the 2 groups were compared. Results All the patients in the two groups were operated smoothly and there were no cases of conversion to open surgery. The operation time, intraoperative blood loss, postoperative ambulation time, time of removal of abdominal drainage tube, and hospitalization time were lower in the study group than those in the control group, but the difference was not statistically significant (P>0.05). The incidence of electrolyte disturbance, postoperative recovery time, and hospitalization cost in the study group were lower than those in the control group, and the difference was statistically significant (P<0.05). The incidence of surgical complications in the study group was lower than that in the control group, but the difference was not statistically significant (P>0.05). Conclusion Laparoscopic combined with choledochoscopy for choledocholithotomy and primary suture in the treatment of intrahepatic and extrahepatic bile duct stones has good curative effect, rapid recovery, less internal environment disorder and low hospitalization cost. It is safe and feasible.

Objective:To determine and investigate the stability of ginkgo biloba extract injection from three different manufactur-ers respectively in 0.9% NaCl infusion and 5% glucose infusion under different conditions (room temperature, high temperature and light). Methods:Ginkgo biloba extract injection was mixed with the two kinds of infusions,and then divided into the normal tempera-ture group,the high temperature group and the light group. The appearance,insoluble particles,pH and content of flavonoids after the relevant treatment were investigated. The appearance and insoluble particles were tested according to the characteristics of the inspec-tion method described in Chinese Pharmacopoeia(2015 edition,volume IV,the general rule),and the content of flavonoids was detec-ted by HPLC-UV. Results:All the mixed solutions were yellow. No significant changes were found in the appearance,pH value,in-soluble particles and contents of quercetin and isorhamnetin in all the mixed solutions in 24 h. The pH value of the mixed solution with 5% glucose infusion was lower than that with 0.9% NaCl infusion,and all the pH values met the standard in Chinese Pharmacopeias. The kaemphenol content in the injection from Shenwei pharmaceutical company was higher than that from the other manufacturers, while the content of kaemphenol in all the injections was within the standard range. Conclusion:The quality of Ginkgo biloba extract injection from the three different manufacturers is stable under different conditions.

A new method for chiral separation and purity inspection of landiolol hydrochloride and its stereoisomers was developed by ultra-performance convergence chromatography ( UPC2 ) . The mobile phase was the mixture of supercritical CO2 and methanol/n-butyl alcohol/acetonitrile (1:1:1, V/V) plus 0. 5%NH3?H2O. The separation was carried out on the Daicel CHIRALPAK? IF column (150 mm × 4. 6 mm, 3 μm) with a flow rate of 2. 8 mL/min at 50℃ using 223 nm as detection wavelength. Under the optimized experimental conditions, for R,R-stereoisomer, R,S-stereoisomer and S,R-stereoisomer, the detection limits (LOD, S/N=3) were 0. 3, 0. 4 and 0. 3 mg/L, the linear ranges were 2-300 mg/L, 5-300 mg/L and 2-300 mg/L, the recoveries of spike samples were 103. 4%±2. 5%, 91. 8%±2. 5% and 101. 7%±1. 5%, and the injection repeatabilities were 0. 06%, 0. 09% and 0. 08% (n=6), respectively. The experimental results demonstrate that the UPC2-based method can be used for the analysis and determination of landiolol hydrochloride and its stereoisomers.

Objective To analyze the distribution characteristics of Pseudomonas aeruginosa and Acinetobacter baumannii ,and to investigate the changing pattern of antimicrobial resistance of these strains isolated during 2012 - 2014 .Methods Strains of Pseud‐omonas aeruginosa and Acinetobacter baumannii isolated from January 2012 to December 2014 were collected .Antimicrobial suscep‐tibility of clinical isolates was tested by Kirby‐Bauer method .Results In the past three years ,214 strains of Pseudomonas aerugino‐sa and 347 strains of Acinetobacter baumannii were isolated .The nosocomial infection rate of Pseudomonas aeruginosa decreased year by year ,while the Acinetobacter baumannii ′s increased .Most strains were isolated from sputum ,wound secretion and urine . The strains of Pseudomonas aeruginosa and Acinetobacter baumannii were distributed in various departments of the hospital .The detection rates of these strains were the highest in ICU ,respectively 27 .6% and 34 .9% .Both the resistance rates of Pseudomonas aeruginosa to ceftazidime ,imipenem ,Amikacin and Acinetobacter baumannii to Piperacillin/Tazobactam and imipenem had in‐creased ,while the resistance rates of Acinetobacter baumannii to polymyxin B had decreased with each passing year .Conclusion Pseudomonas aeruginosa and Acinetobacter baumannii causes severe nosocomial infections and the antimicrobial resistance rates in‐creased ,especially the resistance rates to carbapenem are becoming more higher in recent years .Acinetobacter baumannii shows strong antibacterial activity in vitro to Polymyxin B .Therefore ,antimicrobial resistance surveillance should be strengthened to direct rational use of antibiotics .