Objective To develop a liquid chromatography technique coupled with tandem mass spectrometry(LC-MS/MS)for simultaneous determination of four active catechins EGCC,ECG,EGC,and EC of tea polyphenols(TP)in rat plasma in order to further study its multi-component pharmacokinetics.Methods Following a single step liquid-liquid extraction of plasma samples with ethyl acetate,the four catechins were separated on a Hypersil ODS C18 column using an isocratic mobile phase composed of methanol-water(30:70).The detection using a mass spectrometer was performed under negative ESI in the MRM mode.The analytes were identified by reference to both MRM and tR values and quantified using peak area internal standard method.Results The method was shown to be specific without interference from matrix,metabolites,and impurities present in TP raw material and to be sensitive with LOD and LOQ of 1.5 and 10 ng/mL(EGCG)as well as 0.75 and 5 ng/mL(ECG,EGC,and EC).A good linearity was obtained over a wide range of 10-10000 ng/mL for EGCG and 5-5000 ng/mL for other three catechins(r > 0.996).The method was validated to be reproducible and reliable,as evidenced by intra-batch and inter-batch precision of less than 10% and 11%,accuracy of 97.13%-106.05% and 99.22%-103.14%,respectively.The recovery of extraction ranged from 72.74% to89.13%,matrix effect from 88.76% to 105.97% for four cateckins.The method was successfully used to study the pharmacokinetics of TP iv administered to rats at a dose of 100 mg/kg.Conclusion This method is shown to completely meet requirements for the multi-component pharmacokinetic study of TP in rats.

Most of the current experiments are obsolete and verified,the students are not interested in and the experiments are out of touch with the actual work.These are the common problems in the experiment teaching of occupational health and occupational medicine.By taking the students who majored in preventive medicine as the subjects,this study aimed to explore the effects of independent designed experiment teaching mode,which was based on dividing the groups before class,choosing the projects by students themselves,deciding the design of the program via the discussion of teacher and students and doing the experimental reports and sharing the experience.The results showed that,in the premise of the preliminary master of the theory and basic skills of occupational health and occupational medicine,carrying out independent designed experiments in the last three weeks of semester,to a certain extent,could arouse students' interest in learning,cultivate their abilities of independent thinking,practice,problem analysis and solution,and team cooperation.However,restricted by lack of teachers,inadequate equipment and high cost and other factors,this teaching mode is only suitable for small class.

Objective:To identify the transmission relationship between HIV infection cases the non-marital non-commercial heterosexual contact in Zhejiang Province.Methods:When HIV positive was informed during January 2020 to January 2022, the staff conducted an epidemiological investigation to collect cases information on sociodemographic characteristics, mobility information, past HIV testing history, high-risk sexual behaviors, sexual partners, and etcetera. At the same time, 6-8 ml of blood from the new diagnosis of people infected with HIV before antiviral treatment was collected to separate the bleeding plasma. pol gene was amplified by nucleic acid extraction and PCR, sequenced by Sequencer 5.0 software, and Cytoscape 3.6.0 software was used to draw HIV molecular transmission network. Results:From January 2020 to January 2022, 88 HIV infected individuals were found in Pujiang County, of which 74 were transmitted through heterosexual transmission, of which 31 were infected through non-marital non-commercial heterosexual contact. Preliminary case studies have found that three female cases have engaged in unprotected non-marital non-commercial heterosexual contact with one male case. Among the 4 infected individuals, 2 of their spouses tested positive for HIV antibodies. Molecular transmission network monitoring was carried out on 65 newly diagnosed cases of heterosexual transmission with acquired sequences, forming 9 transmission clusters. The largest cluster contained 10 cases. A total of 11 HIV-infected individuals were involved in this HIV cluster epidemic. They were 3 males and 8 females, all over 50 years old and were farmers or rural housewives. They were traced to 7 sexual partners (6 negatives of HIV, 1 undetected). Among the 18 respondents' sexual social network relationships, there were 6 couples, 8 permanent partners, and 3 temporary partners. Among 11 HIV infected individuals, there were 9 cases of non-marital non-commercial heterosexual transmission and 2 cases of intramarital transmission. The epidemiological association between 7 non-married non-commercial heterosexual partners and case 2 (56-year-old male farmer), 3 cases confirmed by epidemiological investigation and molecular transmission cluster results, 3 cases confirmed by molecular transmission cluster and epidemiological investigation results, and 1 case confirmed by epidemiological investigation results.Conclusions:The transmission mode of this cluster epidemic was to spread HIV through heterosexual sex with a male case as the core, then cause the transmission within marriage and between fixed sexual partners. The combination of epidemiological investigation and molecular transmission network traceability survey supports the conclusion of this study.

OBJECTIVE: To explore the genetic basis of cerebral palsy (CP). METHODS: A pair of twins with cerebral palsy and different phenotypes were subjected to whole genome sequencing, and other 8 children with CP were subjected to whole exome sequencing. Genetic variations were screened by a self-designed filtration process in order to explore the CP-related biological pathways and genes. RESULTS: Three biological pathways related to CP were identified, which included axon guiding, transmission across chemical synapses and protein-protein interactions at synapses, and 25 susceptibility genes for CP were identified. CONCLUSION The molecular mechanism of CP has been explored, which may provide clues for development of new treatment for CP.
Cerebral Palsy ; genetics ; Child ; Genetic Testing ; Humans ; Phenotype ; Whole Exome Sequencing ; Whole Genome Sequencing

Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC 0–24h /MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E max (Hill) equation. The dose was calculated based on the AUC 0–24h /MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. suis infections.

Objective We aimed to explore the clinical efficacy of precise electro-acupuncture stimulation in the pterygopalatine fossa for the treatment of chronic sinusitis.Methods In total,40 patients with chronic sinusitis who visited the Xiyuan Hospital,China Academy of Chinese Medical Sciences between January 2022 and January 2023 were selected.The subjects were randomly divided into two groups:the treatment group(receiving precise electro-acupuncture in the pterygopalatine fossa)and the control group(receiving standard western medical treatment),with 20 cases in each groups.The treatments were administered twice a week for a period of 12 weeks.The effectiveness of the treatments was evaluated through computed tomography(CT)of the sinus changes and the Lund-Mackay scoring system.Results In cases of total opacity and partial opacity,there were significant differences between the two patient groups before and after treatment(P<0.05).Intra-group comparison revealed statistically significant improvements in both groups before and after treatment(P<0.05).The treatment group exhibited significant improvement in various sinus conditions(P<0.05),while in the control group,a significant improvement was only observed in the left maxillary sinus(P<0.05).Inter-group comparison also demonstrated that the treatment group's improvements were superior to those of the control group across multiple indicators(P<0.05).Conclusion The precise electro-acupuncture stimulation technique in the pterygopalatine fossa demonstrated significant therapeutic effects in the treatment of chronic sinusitis,with superior outcomes with respect to radiological changes compared to standard western medicine treatment.

Objective? To expLore the effects of Home FaLL Hazards Assessment (HFHA) on the incidence rate of home faLLs and recovery of hip function in patients receiving totaL hip arthropLasty (THA). Methods? TotaLLy 423 patients who received uniLateraL THA for the first time in the Department of Orthopedics, Nanjing Drum Tower HospitaL admitted from JuLy 2015 to JuLy 2017 were seLected by convenient sampLing and divided into the controL group (n=203) and the treatment group (n=220). Patients in the controL group received conventionaL postoperative nursing care and discharge guidance, whiLe the home faLL hazards of patients in the treatment group were evaLuated by HFHA in addition to conventionaL postoperative nursing care and discharge guidance. Nursing care was provided to them based on the assessment resuLts. The joint function score at discharge and 3 months after discharge, the incidence rate of faLLs over the past one year and the severity of injury caused by faLLs were compared between the two groups. ResuLts? There was no statisticaL difference in Harris index and BartheL index scores between the two groups at discharge (P＞ 0.05). Harris index and BartheL index scores 3 months after discharge were statisticaL differences in both groups (P＜0.05). 55 faLLs occurred over the past one year in the controL group, 7 of them with moderate or above injuries, whiLe 35 faLLs occurred over the past one year in the treatment group, 1 of them with moderate or above injuries. There were statisticaL differences in the incidence rate of faLLs and injury degrees between the two groups (P＜0.05). ConcLusions? HFHA, when used to assess the home faLL hazards, enabLes THA patients to know and note the high-risk hazards contributing to faLLs in their environment of rehabiLitation and effectiveLy reduces the patients home faLLs by improving the home environment.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.