According to General Chapter 1145 of Division IV in the Chinese Pharmacopoeia (2020 Edition), the test for depressor substances is a common method for drug testing. It determines whether the level of depressor substances in a test sample complies with the specified standards by comparing the extent of blood pressure reduction in anesthetized cats induced by the histamine reference substance and the test sample. If an out-of-specification (OOS) result occurs in the test for depressor substances, it may be caused by inherent quality issues of the drug or errors in the testing process. Therefore, analyzing the causes of OOS is particularly important for confirming the test results and evaluating drug quality. Cats are used as experimental animals in the test for depressor substances. Compared with conventional laboratory animals, they are less stable, surgery procedures are more challenging, and the testing process is more complex. These factors make it more difficult to investigate the causes of OOS in this test. Based on a review of the literature and practical work experience, this article analyzes the causes of OOS in the test for depressor substances from the following five aspects: (1) an analysis of the impact of drug standards on OOS from three aspects: standard determination, standard content, and standard drafting; (2) personnel qualifications, including pre-employment training, compliance with standard operating procedures during experimental operations, and the ability to operate instruments; (3) factors related to cats, used as experimental animals in the test for depressor substances, including physiological characteristics, genetic background, and abnormal conditions during the experiment; (4) reference substances, reagents, test samples, and key instruments such as the multi-channel physiological signal instrument; (5) experimental operations including animal anesthesia, arterial and venous catheterization, drug administration, and data processing. This article aims to provide reference approaches for professionals engaged in the testing of pharmaceuticals and biological products when analyzing the causes of OOS in the test for depressor substances.

According to General Chapter 1145 of Division IV in the Chinese Pharmacopoeia (2020 Edition), the test for depressor substances is a common method for drug testing. It determines whether the level of depressor substances in a test sample complies with the specified standards by comparing the extent of blood pressure reduction in anesthetized cats induced by the histamine reference substance and the test sample. If an out-of-specification (OOS) result occurs in the test for depressor substances, it may be caused by inherent quality issues of the drug or errors in the testing process. Therefore, analyzing the causes of OOS is particularly important for confirming the test results and evaluating drug quality. Cats are used as experimental animals in the test for depressor substances. Compared with conventional laboratory animals, they are less stable, surgery procedures are more challenging, and the testing process is more complex. These factors make it more difficult to investigate the causes of OOS in this test. Based on a review of the literature and practical work experience, this article analyzes the causes of OOS in the test for depressor substances from the following five aspects: (1) an analysis of the impact of drug standards on OOS from three aspects: standard determination, standard content, and standard drafting; (2) personnel qualifications, including pre-employment training, compliance with standard operating procedures during experimental operations, and the ability to operate instruments; (3) factors related to cats, used as experimental animals in the test for depressor substances, including physiological characteristics, genetic background, and abnormal conditions during the experiment; (4) reference substances, reagents, test samples, and key instruments such as the multi-channel physiological signal instrument; (5) experimental operations including animal anesthesia, arterial and venous catheterization, drug administration, and data processing. This article aims to provide reference approaches for professionals engaged in the testing of pharmaceuticals and biological products when analyzing the causes of OOS in the test for depressor substances.

Objective:To explore the teaching effect of combining diversified teaching modes with individualized teaching methods in musculoskeletal ultrasound training classes compared with traditional teaching modes.Methods:The 109 trainees participated in the muscle and bone ultrasound training classes from June 2020 to June 2022 were included as the research subjects and divided into the observation group ( n=53) and control group ( n=56). The control group received traditional teaching modes, while the observation group received diversified teaching modes in combination with individualized teaching methods. The differences in teaching satisfaction and final exam scores between the two groups were compared after training. Statistical analysis was conducted using the software SPSS 27.0. Categorical data were presented as cases and percentages, while continuous data were presented as mean±standard deviation. The intergroup differences in continuous variables were compared using the t-test, while the intergroup differences in categorical variables were compared using the chi-square test. Results:There were no significant differences in age, sex, education, and professional title between the control group and the observation group ( P>0.05). The comprehensive satisfaction score of ultrasound teaching was (88.08±6.65) in the observation group and (80.71±8.59) in the control group, with a significant difference between the two groups ( χ2=5.02, P<0.01). Before training, the test scores of the control group and the observation group were (62.61±5.39) and (63.87±7.77), respectively, and there was no significant difference between the two groups ( t=0.98, P=0.330). The final scores, theoretical exam, computer operation, and video reading exam scores of the control group were (84.07±1.49), (82.39±1.97), (85.13±2.55), and (86.79±6.06), respectively, while those of the observation group were (90.06±2.17), (88.28±3.19), (88.92±3.23), and (96.23±5.96); there were significant differences between the two groups in these four indicators ( t=16.75, 11.53, 6.79, and 8.20, respectively; P<0.01). The scores were compared for the two groups of trainees classified based on their unit level, professional title, and educational background. Trainees with the same unit level, professional title, and educational background showed no significant differences in test scores between the two groups, though their final scores were significantly different ( P<0.01). Conclusions:The combination of diversified teaching modes and individualized teaching methods can increase the learning enthusiasm of trainees, improve the teaching effect of training classes, and increase the satisfaction of trainees.

Kirsten rat sarcoma viral oncogene homolog(KRAS)gene is one of the most commonly mutated oncogenes.It has been found that KRAS inhibitors have the potential therapeutic effect on cancer patients with this gene mutation.In this study,machine learning was applied to develop a QSAR(quantitative structure-activity relationship)model for KRAS small molecule inhibitors.A total of 1857data points of IC50 and SMILES(simplified molecular input line entry system)for KRAS inhibitors were collected from three databases:ChEMBL,BindingDB,and PubChem.And nine different classifiers were constructed using three different feature screening methods combined with three machine learning models,namely,random forest,support vector machine,and extreme gradient boosting machine.The results showed that the SVM model combined with mutual information feature selection exhibited the best performance:AUCtest=0.912,ACCtest=0.859,F1test=0.890.Moreover,it also demonstrated good predictive performance on the external validation set(AUCExt=0.944,RecallExt=0.856,FPRExt=0.111).This study provides a new technical route for KRAS inhibitor screening in natural product databases using artificial intelligence methods.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

BACKGROUND: The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC. METHODS: 46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC. RESULTS: Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC. CONCLUSIONS Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.
Humans ; Male ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Programmed Cell Death 1 Receptor/genetics* ; Retrospective Studies ; Antineoplastic Agents, Immunological/therapeutic use* ; Prognosis ; DNA Helicases/genetics* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Administration, Intravenous ; Ascorbic Acid/therapeutic use* ; COVID-19 ; Humans ; Pneumonia ; SARS-CoV-2

Objective To analyze the changes of CD4⁺ T cell numbers at different periods of antiviral therapy in HIV-infected and AIDS patients (HIV/AIDS) in Yichang City. Methods The relevant information was retrieved from the National AIDS Comprehensive Prevention Information System-Antiretroviral Treatment Management Database. Changes in the number of CD4⁺ T cells were analyzed in HIV/AIDS patients who started receiving highly active antiretroviral therapy (HAART) and continued the treatment for 3 years from January 1, 2003 to December 31, 2017 in Yichang. Results The number of CD4⁺T lymphocytes in 550 HIV/AIDS cases increased significantly at various time points within 3 years after treatment, and increased with the increase of treatment time（F=100.20，P<0.001）. The CD4+T cell counts of different baseline level groups were statistically different before and after treatment（F=8.57，P<0.01）. The CD4+ T cell counts of patients who started treatment at age of 15-30 years old increased faster than those who started treatment at age of over 30 years old（F=1.27，P<0.05）. Conclusion HAART has a significant effect on the increase of CD4+T cells, and the early treatment is more effective. Early detection, diagnosis and treatment should be promoted, and anti-viral treatment should be actively carried out.

In order to improve the cure rate of critically ill patients in Wuhan epidemic area and reduce the fatality rate, the state have dispatched medical staffs from the whole country to support Wuhan and treat critically ill patients in dedicated facilities. A medical team from the First Affiliated Hospital of Xi’an Jiaotong University, consisting of 133 medical staffs major in critical care medicine, respiralogy, infection, cardiology, and general surgery, entirely took over the critical care unit of the East Hospital of the Renmin Hospital of Wuhan University, and formed a multidisciplinary collaboration team with local medical staffs to treat patients together. Up to March 13th in 2020, the author′s medical team has admitted a total of 109 patients, of which 48 had been discharged up on recovery. Critically ill patients with Corona Virus Disease 2019 mainly have elder age, comorbidities, complicated conditions, and difficult diagnosis and treatment. The author and the author′s team combined with clinical practice, share experience and strategies of general surgery related issues in the treatment of critically ill patients, providing reference for collegues in general surgery.

Objective To investigate the clinical effect of ibuprofen on preventing intracranial hemorrhage in premature infants and its influence on the levels of NT-proBNP and ET-1.Methods From January 2016 to December 2017,112 premature infants in Taizhou Hospital were selected as study objects after screening by inclusion and exclusion criteria.The infants were randomly divided into observation group and control group according to the digital table,with 56 cases in each group.The control group was treated with routine therapy,and the observation group was given ibuprofen prophylaxis.The incidence of intracranial hemorrhage,clinical index and serum NT-proBNP,ET-1 levels were compared between the two groups.Results There was significant difference in the incidence rate of intracranial hemorrhage between the observation group (17.86％) and the control group (30.36％)(x2 =12.472,P ＜0.05).The serum levels of NT-proBNP and ET-1 in the observation group were significantly lower than those in the control group(all P ＜ 0.05).There were no statistically significant differences in liver function,renal function,coagulation abnormality and oliguria between the two groups (all P ＞ 0.05).There were no statistically significant differences in feeding intolerance and gastric hemorrhage between the two groups (all P ＞ 0.05).Conclusion The application of ibuprofen suspension can effectively prevent intracranial hemorrhage in premature infants,which is worthy of clinical use.