ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata（ARLP） in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group， model group， Shengfupian（SFP） group， Paofuzi（PFZ） group， Heishunpian（HSP） group and Paofupian（PFP） group with 6 rats in each group. Except for the control group， rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days， each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg^-1·d^-1 for 7 d， while the control and model groups received an equivalent volume of physiological saline. After the end of administration， body weight， spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol（TC）， triglyceride（TG）， lactic dehydrogenase（LDH） and lactate（LAC） levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the contents of 17-hydroxycorticosteroid（17-OHCS）， cortisol（CORT）， triiodothyronine（T₃）， thyroxine（T₄）， thyrotropin（TSH）， immunoglobulin（Ig） M， IgG， cyclic adenosine monophosphate（cAMP） and cyclic guanosine monophosphate（cGMP）. Western blot was used to measure the protein expression levels of protein kinase A（PKA）， cAMP response element-binding protein（CREB）， silent information regulator 1（Sirt1） and peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）. And high performance liquid chromatography（HPLC） was used to determine the content of major alkaloids， followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling， compare with the control group， the model rats exhibited symptoms such as lethargy and loose stools， mild abnormalities were observed in adrenal tissue structure， and both spleen and thymus indices were significantly reduced（P<0.01）. Thyroid， adrenal and immune system functions were suppressed， with decreased serum cAMP level and significantly elevated cGMP level（P<0.01）. Compared with the model group， the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups（P<0.05， P<0.01）. The thymus index in SFP and PFZ groups were increased significantly（P<0.05）. The contents of T₃， TSH， 17-OHCS and CORT were increased significantly in SFP and PFZ groups（P<0.05）. In addition， the content of IgG in SFP， PFZ and PFP groups were increased significantly（P<0.01）， while the content of IgM in PFZ and HSP groups were also increased significantly（P<0.05）. Regarding the cyclic nucleotide system， PFZ significantly elevated cAMP level while reducing cGMP level（P<0.05）， exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators， PFZ significantly improved abnormal markers including TC， TG， LDH， and LAC（P<0.05）. HSP showed marked improvement effects on TG， LDH， and LAC（P<0.05）. Both PFZ and SFP significantly elevated the expression levels of PKA， CREB， Sirt1， and PGC-1α proteins（P<0.01）. Additionally， the diester alkaloids in ARLP showed a strong positive correlation with TG， IgG， and CORT， a strong negative correlation with LAC， a moderate positive correlation with T₄， and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG， strong negative correlations with LAC， moderate positive correlations with CORT and T₄， and moderate negative correlations with cAMP and spleen index. However， the content of water-soluble alkaloids showed strong positive correlations with TC， LDH， 17-OHCS， T₃， TSH， and thymus index， moderate positive correlations with cAMP， CORT， T₄， and spleen index， and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces， PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid， adrenal， immune， cyclic nucleotide systems， and material-energy metabolism pathways. Among these， water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore， PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.

ObjectiveTo analyze scarlet fever surveillance data in Harbin City from 2010 to 2024, to preliminarily understand its incidence level and epidemiological characteristics, and to provide a scientific basis for the further formulation of effective prevention and control strategies. MethodsScarlet fever surveillance data for Harbin City from January 1, 2010 to December 31, 2024 were collected through the China Disease Prevention and Control Information System. Descriptive epidemiological analyses were conducted using incidence rates and constituent ratios. ResultsFrom 2010 to 2024, a total of 11 052 scarlet fever cases were reported in Harbin City, during the 15-year period, with an average annual reported incidence of 7.65/100 000. The overall annual incidence rate showed a fluctuating downward trend, with epidemic peaks occurring from April to July each year and from November to January of the following year. The age group of 0 to 9 years had the highest incidence rate at 6.47/100 000. The majority of cases were students (4 707 cases, 42.59%), children in nurseries and kindergartens(3 289 cases, 29.76%) and scattered children (2 941 cases, 26.61%), together accounting for 98.96% of all cases. The incidence ratio of male to female was 1.53∶1. The average annual incidence rate was 9.23/100 000 for males and 6.07/100 000 for females. Over the 15-year period, all 18 districts (counties) in Harbin City had reported cases. The top five areas with the highest average annual reported incidence of scarlet fever were Acheng District (14.45/100 000), Xiangfang District (12.73/100 000), Pingfang District (12.10/100 000), Bin County (10.29/100 000) and Daowai District (10.08/100 000). ConclusionFrom 2010 to 2024, the overall incidence of scarlet fever in Harbin City presented a downward trend. The disease prevailed mainly in spring-summer and autumn-winter, rather than year-round, with cases concentrated in densely populated districts and counties. Children and adolescents constituted the major affected population. The incidence was slightly higher in males, and school-age children accounted for a larger proportion than other age groups. Comprehensive preventive measures should focus on health education in key endemic areas, strengthen targeted protection for high-risk groups, and enhance epidemic surveillance and early warning.

Pharmacovigilance runs through the whole life cycle of drugs. This paper systematically sorts out the development course of pharmacovigilance in China， from the initial establishment of the adverse drug reaction reporting system to the gradual construction of a complete pharmacovigilance system aligned with international standards. It focuses on analyzing the evolutionary features of the organizational system， legal system and monitoring system during this process. On this basis， this paper further discusses the future development trends of pharmacovigilance in China. In general， remarkable progress has been achieved in both regulatory construction and practical implementation of China’s pharmacovigilance system. In the future， efforts should be continuously made to improve the pharmacovigilance system， such as accelerating the implementation of the “one-body with two-wings” working framework and strengthening the primary responsibility of marketing authorization holders. It is also necessary to cultivate and reserve professional talents and promote information-based construction， including optimizing the spontaneous reporting system and establishing active monitoring systems. These measures can provide more solid support for ensuring public drug safety and facilitating high-quality development of the pharmaceutical industry.

ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT （DLCT） parameters in predicting lymph node metastasis （LNM） of non-functional pancreatic neuroendocrine neoplasms （NF-pNENs）. MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest （ROIs） were manually delineated on three representative slices of the solid component of the lesion， and the mean values were recorded. Conventional CT parameters， monochromatic energy images （40 keV， 70 keV， 100 keV）， iodine concentration maps， and effective atomic number （Z_eff） maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters， including clinical characteristics， imaging features， conventional CT and DLCT quantitative parameters， were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator （LASSO） regression. Receiver operating characteristic （ROC） curves were generated for each predictive model， and the area under the curve （AUC） was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled， including 37 males and 45 females， with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression， LASSO regression and multivariate stepwise logistic regression analyses， body mass index （BMI）， organ invasion， normalized CT value in the portal venous phase （nCTv） and normalized iodine concentration in the portal venous phase （nICv） were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model （BMI+organ invasion）， conventional CT model （nCTv）， DLCT model （nICv） and comprehensive model （organ invasion+nICv） were 0.815 （0.719， 0.910）， 0.750 （0.642， 0.858）， 0.829 （0.733， 0.925） and 0.865 （0.879， 0.953）， respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs， enabling non-invasive preoperative prediction and assisting clinical decision-making.

ObjectiveTo investigate the value of preoperative dual-layer spectral detector CT （DLCT） parameters in predicting lymph node metastasis （LNM） of non-functional pancreatic neuroendocrine neoplasms （NF-pNENs）. MethodsA retrospective study was conducted on patients with pathologically confirmed NF-pNENs who underwent preoperative contrast-enhanced DLCT examination between September 2019 and July 2024. Regions of interest （ROIs） were manually delineated on three representative slices of the solid component of the lesion， and the mean values were recorded. Conventional CT parameters， monochromatic energy images （40 keV， 70 keV， 100 keV）， iodine concentration maps， and effective atomic number （Z_eff） maps in the pancreatic parenchymal phase and portal venous phase were acquired. A total of 34 parameters， including clinical characteristics， imaging features， conventional CT and DLCT quantitative parameters， were analyzed. Intergroup differences were compared between the LNM and non-LNM groups. Independent predictive factors were screened using logistic regression and least absolute shrinkage and selection operator （LASSO） regression. Receiver operating characteristic （ROC） curves were generated for each predictive model， and the area under the curve （AUC） was calculated to evaluate the predictive efficacy. ResultsA total of 82 patients with NF-pNENs were enrolled， including 37 males and 45 females， with a mean age of 49.7±14.7 years. Thirty patients were performed with LNM and 52 were with non-LNM. After univariate logistic regression， LASSO regression and multivariate stepwise logistic regression analyses， body mass index （BMI）， organ invasion， normalized CT value in the portal venous phase （nCTv） and normalized iodine concentration in the portal venous phase （nICv） were identified as independent predictive factors. The AUCs of the clinical-radiological qualitative model （BMI+organ invasion）， conventional CT model （nCTv）， DLCT model （nICv） and comprehensive model （organ invasion+nICv） were 0.815 （0.719， 0.910）， 0.750 （0.642， 0.858）， 0.829 （0.733， 0.925） and 0.865 （0.879， 0.953）， respectively. The comprehensive model combining clinical-radiological and DLCT characteristics exhibited superior predictive performance. ConclusionDLCT parameters are more effective than conventional CT parameters in predicting LNM in NF-pNENs， enabling non-invasive preoperative prediction and assisting clinical decision-making.

Objective To identify candidate compounds that activate thermogenesis during cold exposure by integrating the Library of Integrated Network-Based Cellular Signatures(LINCS)with RNA expression profiles specific to cold-induced thermogenesis.Methods Gene expression profiles of interscapular brown adipose tissue(BAT)and inguinal white adipose tissue(iWAT)were generated from 8-week-old C57BL/6J mice which were housed at 5 ℃ or room temperature(23 ℃)for 7 days.The gene expression signatures of the cold-induced BAT and iWAT were compared to the LINCS dataset to predict potential candidates for testing in a cold challenge model that was intended to assess thermogenesis activation.The pharmacological potential of the identified compounds was evaluated in a cold-exposed mouse model.The core body temperature and infrared thermal imaging were collected to monitor physiological responses during cold exposure.Additionally,hematoxylin and eosin(HE)staining was used to assess morphological changes of fat cells of BAT,iWAT,and epididymal white adipose tissue(eWAT).Results The transcriptomic signatures related to cold-induced thermogenesis were obtained and the top 20 candidate compounds were identified by comparison with the LINCS dataset.Mice treated with withaferin A(WA)during the cold challenge exhibited elevated rectal temperatures and smaller adipocyte sizes compared to controls.Conclusion Our drug repurposing strategy,which connects transcriptional profiles with LINCS data,identifies potential compounds.WA enhances thermogenesis and metabolic activity in adipose tissue,which helps maintain body temperature,and improves cold tolerance during exposure to low temperatures.

Objective : To explore the role and mechanism of 25-hydroxycholesterol (25-HC) in inflammatory bow- el disease (IBD) in mice． Methods : All mice were divided into three groups : the control group was fed normally ; the DSS model group was fed with 2. 5% dextran sulfate sodium (DSS) solution ; the DSS + 25-HC experimental group was fed with 2. 5% DSS solution and he mice in the experimental group were intraperitoneally injected with 25-HC．The symptom changes of the mice were evaluated by assessing the disease activity index(DAI) ，and the tis- sue changes were judged by histological scoring．The expression of interleukin-17 and its signaling pathways in the mice were detected by Western blot，qRT-PCR, immunohistochemistry /fluorescence，and flow cytometry．Combined with the detection of tight junction proteins in the intestinal epithelium of the mice，the mechanism by which 25-HC affects IBD in mice was explored． Results : In comparison to the DSS control group，The DSS + 25-HC experimen- tal group mice exhibited a reduction in body weight ( F = 30. 1，P ＜0. 000 1) ，a shortened colon ( F = 63. 8，P < 0. 05) ，and elevated DAI(F = 774. 5，P＜0. 000 1) and histopathological scores(F = 141. 5，P＜0. 05) ．Addition- ally，the expression of tight junction-associated proteins(ZO-2，Occludin，JAM and Claudin-4) was found to be sig- nificantly reduced．The level of IL-17 significantly decreased，and its expression level was positively correlated with tight junction proteins． Conclusion 25-HC inhibited IL-17 production by colonic γδ T cells through the RORγt pathway，aggravated mucosal injury，and promoted the development of DSS-induced acute colitis in mice．

Objective:To understand the prevalence and related factors of three common chronic diseases, hyperlipidemia, hypertension and diabetes in HIV-infected persons.Methods:As of December 2023, HIV-infected persons >15 years old who are receiving antiviral therapy (ART) and follow-up in Henan Province were selected as the study objects. Questionnaires, physical examinations, and blood samples were collected to collect demographic information, ART, body weight, blood lipids, blood pressure, and blood sugar of HIV-infected persons. The logistic regression model was used to analyze the related factors of hyperlipidemia, hypertension and diabetes.Results:Among 4 023 HIV-infected patients, the prevalence rates of hyperlipidemia, hypertension, and diabetes were 64.47% (2 594/4 023), 16.80% (676/4 023), and 10.54% (424/4 023), respectively. Multivariate analysis showed that hyperlipidemia was positively associated with ≥40 years of age, overweight and obesity, two nucleoside reverse transcriptase inhibitors (NRTIs) + proteasome inhibitors (PIs) regimen and two NRTIs+ integrase inhibitor regimen, and negatively associated with low body weight. Hypertension was positively correlated with the age group ≥40 years old, family history of cardiovascular and cerebrovascular diseases, overweight and obesity, ART time ≥0.5 years, and negatively correlated with low body weight. Diabetes was positively associated with age group ≥40 years, family history of cardiovascular and cerebrovascular disease, overweight and obesity, and negatively associated with the use of two NRTIs+PIs treatment regimens.Conclusions:In 2023, the prevalence of hyperlipidemia, hypertension, and diabetes among HIV-infected people in Henan Province was relatively high, and the risk of common chronic diseases among those ≥40 years old, overweight and obese, and those with a family history of cardiovascular and cerebrovascular diseases was also relatively high. It is recommended to strengthen the prevention and management of common chronic diseases among HIV-infected people.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

AIM:This study aims to investigate the role of histone methyltransferase SET and MYND domain containing 2(SMYD2)in facilitating renal fibrosis through the macrophage-myofibroblast transition in diabetic kidney dis-ease(DKD).METHODS:(1)C57BL/6J mice were intraperitoneally administered 55 mg/kg of streptozotocin to induce diabetes mellitus(DM).The experimental groups were categorized as follows:normal control,DM(20 weeks),DM(28 weeks),and DM(36 weeks).Blood glucose(BG),serum creatinine(SCr)and blood urea nitrogen(BUN)levels were determined using a biochemical analyzer.Hematoxylin-eosin(HE)staining and Masson staining were performed to assess morphological and fibrotic changes in renal tissues.Western blot analysis was used to measure the protein levels of SMYD2,histone H3 lysine 4 trimethylation(H3K4me3),arginase-1,matrix metalloproteinase 9(MMP9),collagen type Ⅰ(Col Ⅰ)and α-smooth muscle actin(α-SMA).Immunofluorescence staining was conducted to examine the localization and expression of F4/80,α-SMA,SMYD2,CD86,CD206 and CD163.(2)Mouse monocyte/macrophage RAW264.7 cells were cultured in vitro and assigned to groups as follows:normal glucose(NG)+negative control siRNA(siNC),high glucose(HG)+siNC,NG+SMYD2 siRNA(siSMYD2),and HG+siSMYD2.Western blot analysis was used to assess the expression of relevant proteins.RESULTS:(1)Compared with normal control group,the levels of BG,SCr and BUN were significantly elevated in DM(28 weeks)and DM(36 weeks)groups(P＜0.05).Renal tissue exhibited tubular atro-phy,dilation,and collagen fiber deposition.The levels of H3K4me3,arginase-1,MMP9,Col Ⅰ and α-SMA proteins were up-regulated(P＜0.05).The CD86,CD206,CD163 and F4/80 were primarily localized in the interstitial macrophages of the renal tubules,α-SMA was predominantly detected in the renal interstitium,and SMYD2 was mainly expressed in renal tubular epithelial cells and the renal interstitium.(2)Compared with NG+siNC group,the protein levels of SMYD2,H3K4me3,arginase-1,CD163,Col Ⅰ,α-SMA,transforming growth factor-β1(TGF-β1)and p-Smad3 in the cells of HG+siNC group were significantly increased(P＜0.05).Knockdown of SMYD2 resulted in a reduction of these indicators(P＜0.05).CONCLUSION:The SMYD2 protein appears to facilitate renal fibrosis in DKD by promoting the macrophage-myofibroblast transition,potentially through the modulation of TGF-β1/Smad3 signaling pathway.