Objective: To establish a high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS) method for the determination of PA-824 in the plasma of Beagle dogs, and study the pharmacokinetics of PA-824 in Beagle dogs. Methods:Carbamazepine was used as the internal standard, and the plasma samples were pretreated with ethyl acetate for the liquid-liquid extraction of PA-824. An Eclipse Plus C18 column (100 mm × 2. 1 mm, 3. 5 μm) was used with the mobile phase consisting of methanol-water (90 :10). The flow rate was 0. 6 ml·min-1 and the column temperature was 30 ℃. The injection volume was 5 μl and the sample analysis time was 5 min. The determination was performed with an electrospray ionization ( ESI) source in the positive multiple reaction monitoring (MRM) mode. The ion pairs were m/z 360. 1→m/z 175. 0 (collision energy of 35, solution cluster volt-age of 65) for PA-824 and m/z 237. 2→m/z 194. 0 (collision energy of 28, solution cluster voltage of 83) for carbamazepine. After the oral administration, PA-824 in plasma was measured at different time points, and then the pharmacokinetic parameters were calcu-lated by DAS 2. 0 software. Results: PA-824 showed a good linear relationship within the range of 50-10000 ng · ml-1 ( r =0. 9991). The recovery was 97. 7%-105. 1%, and the RSDs of intra-day and inter-day were less than 5. 0%. At three different dosa-ges (100, 200 and 500 mg) of PA-824, AUC0-twere (5735. 18 ± 1918. 76),(11548. 47 ± 1838. 04) and (21987. 88 ± 4587. 58) ng·min·ml-1,t1/2 were(14.17 ±5.97),(11.11 ±4.39) and (13.13 ±5.46)h,and Cmaxwere(626.66 ±188.48),(2399.13 ± 516.51) and (4861.33 ±2253.61)ng·ml-1, respectively. Conclusion:The method is simple, accurate, rapid and reproducible, and suitable for the pharmacokinetic study of PA-824 in the plasma of Beagle dogs.

Objective:To discover the epidemiological characteristics and clinical manifestations of Nontyphoidal Salmonella(NTS) infection in children suffering from diarrhea in Guangzhou, and to provide references for the prevention and treatment of salmonella infection. Methods:A total of 570 diarrhea children and 296 non-diarrhea controls were collected with stratified sampling from three districts of Guangzhou Women and Children′s Medical Center from January 2019 to December 2019. Through bacterial culture, corresponding colonies were selected and Salmonella diagnostic serum was applied for preliminary serum diagnosis, and then systemic biochemical method was adopted for diagnosis. A structured questionnaire was conducted to record the demographic information and clinical symptoms from each subject. Results:The detection rate of NTS was 6.67% (38/570 cases, 95% CI: 4.90%-9.02%) in children with diarrhea, and 1.01% (3/296 cases, 95% CI: 0.34%-2.93%) in children without diarrhea. There were statistically differences in NTS detection rate between children with diarrhea and the control ( χ2=13.805, P<0.05, OR=6.976, 95% CI: 2.135-22.796). There were no significant differences in NTS detection rate between male and female children with diarrhea ( χ2=0.395, P>0.05, OR=1.254, 95% CI: 0.619-2.541). The detection rate of NTS was 5.30% (22/416 cases, 95% CI: 3.52%-7.88%) in children younger than 2 years old, and was 10.40% (16/154 cases, 95% CI: 6.50%-15.21%) in children over 2 years old. There were statistically differences ( χ2=4.700, P<0.05, OR=2.076, 95% CI: 1.060-4.068) between the younger and the older groups.The detection rate of NTS was 5.40% (25/460 cases, 95% CI: 3.70%-7.89%) for children with diarrhea in outpatient department and 11.80% (13/110 cases, 95% CI: 7.04 %-19.18%) for children with diarrhea in inpatient department, with statistically significant differences ( χ2=5.813, P<0.05, OR=2.332, 95% CI: 1.152-4.721). The detection rate of NTS diarrhea in children was 4.60% (10/217 cases, 95% CI: 2.52%-8.28%) in spring, 8.50% (12/141 cases, 95% CI: 4.93%-14.29%) in summer, 9.60% (15/144 cases, 95% CI: 6.41%-16.48%) in autumn and 1.50% (1/168 cases, 95% CI: 0.11%-3.30%) in winter, respectively, with statistically differences among the four seasons( χ2=9.404, P<0.05). There were significant differences in most common clinical symptoms of fever, vomiting, abdominal pain, bloody stool and pasty stool between NTS positive and negative children(all P<0.05). Salmonella enteritis is the main type, and Salmonella typhimurium is the second type. Conclusions:NTS is one of the most important bacterial pathogens and leads to diarrhea in children in Guangzhou city, without differences in gender.Children over 2 years old are more likely to suffer from NTS infection.High incidence is in autumn.The most common clinical symptoms include fever, vomiting, abdominal pain, bloody stool and pasty stool. Salmonella enteritis is the main type, and Salmonella typhimurium is the second type.Laboratory tests can provide references for the diagnosis and treatment of NTS-related diarrhea.

Previous studies have suggested that various kinds of inflammatory factors can influence the formation and development of tumor cells.Researche has shown that gallbladder cancer is closely linked with local inflammation,which is a risk factor for the development of gallbladder cancer.It is widely known that cholecystitis is closely correlated with gallstones,and that bile obtained from patients with gallbladder cancer contains a large variety of bacteria,such as Salmonella typhi,Helicobacter,and Escherichia coli.It is proposed that the gallbladder may be the result of the joint action of inflammation with the bacterial flora.Similarly,the inflammatory “tumor infiltrating lymphocyte” (TIL)can be observed in the tumor and its surrounding tissues,and may also play a role in tumor growth and metastasis.However,detailed mechanisms about the relationship between inflammation and gallbladder cancer is still not clear.No specific anti-inflammatory drugs for gallbladder cancer have been developed. In the near future,anti inflammatory drugs may play a more important role in gallbladder cancer prevention and treatment.

Objective To investigate the inhibitory effect of apigenin-7-o-glucoside (AGL) on the viability of Huh7 cells and tumor growth in Huh7-xenograft tumor nude mice. Methods CCK-8 was used to detect the proliferation inhibitory effect and the half inhibitory concentration of AGL on Huh7 cells. The mitochondrial membrane potential measurement was used to analyze the early apoptosis of Huh7 cells after AGL treatment. Flow cytometry was used to analyze the effect of AGL on Huh7 cell apoptosis, and Western blot was used to explore the expression level of the proteins associated with apoptosis and inflammation, as well as the possible related mechanism. In Huh7-xenograft tumor nude mice, vernier caliper was used to measure tumor volume to analyze the effect of AGL on tumor growth rate. HE staining was used to observe the pathological state of mouse organs, and the inflammation-related factors in serum were detected with ELISA. Results After Huh7 cells were treated with AGL, the mitochondrial membrane potential reduced, the content of ROS increased and the apoptosis rate was increased to 25.23% by 50 μmol/L AGL treatment; while the expression levels of Bax, Bad, Cleaved Caspase-3 and Cleaved Caspase-9 increased, and the expression levels of Bcl2 and Bcl-x^L decreased, the phosphorylation level of NF-κB, IKKα/β and IκBα decreased; the tumor growth rate decreased, the serum IL-6 and TNF-α levels significantly decreased, while the IL-2 and IL-10 levels increased. Conclusion AGL could promote the apoptosis of Huh7 cells and relieve the tumor development in Huh7-xenograft tumor nude mice, which may be related to the NF-κB pathway.

Standardized residency training is the only way for medical students to grow into clin-icians. At present, the number of under training residents in China has reached 190000 (excluding special-ized degree graduate students). It is very important to manage each stage of this training well, which is an guarantee for improving the effect of standardized training. The residents who attend the training are com-posed of "unit personnel" and "intra-industry social personnel", and after standardized and homogenized training, the two types of students have officially become the new force in the medical industry after passing the final examination. In order to do a good job in the management of standardized residency training, to achieve fine management at all stages , this paper focuses on the differences between the two types of students, analyzes in detail the characteristics of these two types of students in the recruitment, training and welfare guarantee stages. "Unit personnel" are given the security, supervision and containment of the origi-nal unit, while due to the pressure of job-hunting and the uncertainty of future welfare, "intra-industry so-cial personnel" are equipped with more initiative. Based on advanced management experience in Beijing,Shanghai, Sichuan and Tianjin, this paper aims to summarize the key points in management of the two types of students in training, propose countermeasures to the difficulties in management, innovative management solutions, and provide reference for the optimization management of standardized residency training.

Objective To observe if VIR576, an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin (a1-AT) which inhibits human immunodeficiency virus type 1 (HIV-1) entry into the target cells by interacting with fusion peptide (FP), can also directly inhibit CD4+T cell activation in vitro. Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation. Both primary CD4+CD25-T cells from DO11.10 mice and CD4+T cell line A2b were activated with specific antigens to evaluate the effects of VIR576. Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation, which bypassed the crosstalk between the CD3-signaling complex and TCR. We furthermore observed that VIR576 could also down-regulate antigen-specific CD4+ T-cell activation. Conclusion Given the high susceptibility of activated CD4+ T cells in the mucosa to HIV-1 infection, the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4+T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.

Tumor immune checkpoint inhibitors (ICIs) present a dual nature, offering therapeutic benefits alongside possible toxic side effects. Despite their significant clinical advantages, immune-related adverse events (irAEs) are major concern. In particular, the multi-organ irAEs (MO-irAEs) caused by ICIs present complex clinical manifestations, affecting a high proportion of critically ill patients. There is a lack of clinical awareness and attention towards these adverse events, making management relatively difficult, thus potentially threatening the life of patients. Reasonable application of hormones and immune modulators, along with symptomatic and supportive treatment, as well as careful monitoring and long-term follow-up are crucial measures to control MO-irAEs. Clinical characteristics, peripheral blood indicators, and genetic predisposition can serve as predictive markers for MO-irAEs occurrence and progression to some extent. A comprehensive understanding of clinical features, intervention measures, prognosis, potential molecular mechanisms and predictive factors of MO-irAEs can help to effectively control MO-irAEs, ultimately improving patient outcomes.

Objective To observe if VIR576, an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin (a1-AT) which inhibits human immunodeficiency virus type 1 (HIV-1) entry into the target cells by interacting with fusion peptide (FP), can also directly inhibit CD4+T cell activation in vitro. Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation. Both primary CD4+CD25-T cells from DO11.10 mice and CD4+T cell line A2b were activated with specific antigens to evaluate the effects of VIR576. Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation, which bypassed the crosstalk between the CD3-signaling complex and TCR. We furthermore observed that VIR576 could also down-regulate antigen-specific CD4+ T-cell activation. Conclusion Given the high susceptibility of activated CD4+ T cells in the mucosa to HIV-1 infection, the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4+T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.

Objective To analyze the predictive value of cone beam computed tomography(CBCT)in styloid process syndrome(SPS)via logistic regression combined with receiver operating characteristic(ROC)curve.Methods A retrospective analysis was conducted on imaging data of 186 patients who underwent styloid CBCT.Among them,65 patients were clinically diagnosed with SPS(patient group),while 121 constituted the healthy controls(control group).The styloid length,inclination angle,and anteversion angle were measured,respectively.Logistic regression analysis was employed,and ROC curves were plotted to calculate sensitivity,specificity,and Youden index,the diagnostic cut-off values for SPS was obtained.Results In the control group,the styloid length was(29.66±7.22)mm,inclination angle was(22.34±3.05)°,and anteversion angle was(31.01±4.13)°.In the patient group,the styloid length was(40.30±8.65)mm,inclination angle was(21.86±3.74)°,and anteversion angle was(35.88±6.37)°.Logistic regression analysis revealed that styloid length and anteversion angle were risk factors for diagnosing SPS(P＜0.05),while inclination angle was not a risk factor for diagno-sing SPS(P＞0.05).ROC curve analysis demonstrated that diagnosing SPS,the area under the curve(AUC),sensitivity,specificity,and optimal cut-off value for styloid length were 0.868,92.3％,69.7％,and 31.23 mm,respectively;and for anteversion angle were 0.765,63.1％,89.3％,and 35.15°,respectively.Conclusion CBCT measurements of styloid length,inclination angle,and antever-sion angle suggest that a styloid length exceeding 31.23 mm and an styloid anteversion angle greater than 35.15° may indicate a higher likelihood of SPS.CBCT is a convenient,cost-effective,and safe diagnostic tool with positive clinical implications.