OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

Objective: To investigate follow-up participation situation, negative conversion, and tuberculosis incidence among boarding junior and senior high school freshmen with latent tuberculosis infection(LTBI) in Zhuhai, so as to provide a reference for better LTBI management in school settings. Methods: A prospective cohort study enrolled 413 LTBI and 27 184 non LTBI boarding junior and senior high school freshmen in Zhuhai from September to October 2023. The LTBI group underwent follow up retesting at >3-6, >6-12, >12-24, >24 months after screening. The followup content included mycobacterium tuberculosis infection testing,chest X ray examination,and questionaire survey(basic demographic information, lifestyle, history of close contact with tuberculosis, and suspected symptoms of pulmonary tuberculosis). Follow-up participation, negative conversion, and tuberculosis incidence were analyzed. Rate was compared by using the Chi-square test, and factors associated with negative conversion were assessed by multivariate Logistic regression analysis. Results: Follow-up participation rates increased initially and then declined, with rates of 25.67% within >3-6 months, 37.05% within >6-12 months, 82.02% within >12-24 months, and 52.21% after 24 months. The overall negative conversion rate was 61.03%. The differences in the conversion rate to negative of mycobacterium tuberculosis infection detection among junior and senior high school freshmen in the LTBI group by different testing methods, school types, smoking history, sleep status, and academic stress were all statistically significant( χ 2=124.96, 22.70, 4.71, 6.31, 6.08, all P <0.05). Multivariate Logistic regression analysis identified testing methods, smoking history, and sleep status as factors associated with negative conversion ( OR =1.90-21.67, all P <0.05). The cumulative incidence of tuberculosis was 726.39 per 100 000 in the LTBI group versus 14.71 per 100 000 in the non-LTBI group ( RR =49.37, 95% CI =11.08-219.87, P <0.01). Conclusions Boarding junior and senior high school freshmen with LTBI in Zhuhai have a higher risk of tuberculosis than concurrent non-LTBI students; they therefore represent a priority group for tuberculosis prevention and control. Centralized follow up is recommended to improve participation, and high specificity methods should be used in follow up retesting and maintain consistency across assessments.

Objective: To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures. Methods: Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC). Results: A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively. Conclusions The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.

Since the 90s of the 20th century, thyroid endoscopic surgery has undergone the development from multi-port to single-site, from endoscopy to robot. In recent years, the emergence of da Vinci single-port robots and domestic single-port robots have further promoted the technological innovation of minimally invasive thyroid surgery. This article reviewed the development process of minimally invasive thyroid surgery from the development of endoscopic thyroid surgery, the breakthrough of single-site endoscopic surgery, and the realization of robotic thyroid surgery and single-port robotic thyroid surgery, and discussed the future of thyroid surgery in the era of artificial intelligence.

Objective To investigate the correlation between changes in physiological indicators and altitude,age,and sex among ethnic Tibetan college students living in Xizang on long-term basis upon their first ever visit to a low-altitude region,thereby providing health guidance for long-term residents of high-altitude regions when they visit low-altitude environments for the first time.Methods A cluster random sampling method was used to select 170 healthy first-year college students of Tibetan ethnicity(85 males and 85 females),from Xizang Minzu University.The participants did not have any respiratory,circulatory,or nervous system diseases,nor any family history of such conditions.Based on their responses to questionnaires and the monitoring data of their physiological indicators,an analysis was conducted to assess the incidence and duration of deacclimatization symptoms among these Tibetan college students during the first month after their arrival at a low-altitude region.In addition,the R programming language and the SPSS software were used to analyze the correlation between changes in blood pressure,heart rate,and body weight and the participants'age,sex,and the altitude of their long-term residence in Xizang before and after their arrival at a low-altitude region.Results Statistical analysis revealed that Tibetan college students experienced deacclimatization symptoms within the first week of their first ever visit to a low-altitude region,primarily characterized by dizziness,fatigue,and drowsiness.The incidence was 41.9％among female students and 22.5％among male students.Furthermore,after arriving at low-altitude region,the participants experience an initial decrease followed by a recovery in both blood pressure and heart rate.They gained an average of 1.5 kg in body mass compared with their initial measurements upon arrival in a low-altitude region.Significant differences in blood pressure,heart rate,and body mass were observed among Tibetan students of different sexes and altitudes of their long-term residence in Xizang after their arrival in a low-altitude region.Conclusion After arriving at a low-altitude region,Tibetan college students exhibit marked changes in physiological indicators,showing strong correlations between systolic blood pressure,body mass,etc.,and sex,altitude,and other parameters.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective:To explore the association between uric acid and new-onset chronic kidney disease (CKD) in middle-aged and elderly hypertensive patients.Methods:This was a retrospective cohort study. Middle-aged and elderly hypertensive patients who had attended at least two annual health examinations at Yongshun Community Health Service Center in Tongzhou District, Beijing, from June 2016 to December 2020 were enrolled. The time interval between the two physical examinations was three years. The first physical examination time served as the baseline, and the second as the end of follow-up. Based on the uric acid level at baseline, the participants were divided into the normal uric acid group and the hyperuricemia group. The relevant clinical data of the participants were collected. The endpoint of the study was new-onset CKD. A multivariate logistic regression model was used to analyze the association between uric acid and new-onset CKD in hypertensive patients.Results:A total of 2 472 middle-aged and elderly hypertensive patients with an average age of (62.43±7.02) years were included. Of these, 733(29.7%) were male. There were 710 patients with hyperuricemia (hyperuricemia group) and 1 762 patients with normal uric acid levels (normal uric acid group).After adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes mellitus, estimated glomerular filtration rate (eGFR), and uric acid-lowering treatment, multivariate logistic regression analysis showed that combined with hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001). The results of multivariate logistic analysis showed that elevated uric acid level was an independent risk factor for new-onset CKD in both male and female middle-aged and elderly hypertensive patients (both P<0.05), and there was no sex interaction ( P for interactio n>0.05). The results of multivariate logistic analysis showed that the combination of asymptomatic hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001), and there was no gender interaction ( P for interactio n>0.05). Conclusions:Hyperuricemia is an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients, and elevated uric acid levels increase the risk of new-onset CKD in both male and female patients. Moreover, asymptomatic hyperuricemia may increase the risk of new-onset CKD.