ObjectiveTo develop an early - warning approach for influenza in Anhui province using the moving epidemic method （MEM）， offering a scientific basis for influenza prevention and control in the province. MethodsBased on the surveillance data reported weekly by influenza sentinel hospitals and network laboratories in the “China Influenza Surveillance Information System”， the weekly influenza virus detection positive rate （positive rate， PR） across the province was analyzed. The MEM was used to estimate the epidemic threshold and classification intensity threshold of influenza in Anhui province before and after the COVID-19 pandemic， respectively. The early warning effect of the MEM was evaluated using cross-validation. ResultsEpidemic and graded intensity thresholds of influenza were derived using PR and MEM. Prior to the COVID-19 pandemic， the starting， medium-intensity， high-intensity， extremely-high-intensity， and ending thresholds of influenza epidemics were 17.08%， 38.47%， 53.20%， 59.71%， and 12.34% respectively. At this point， the model exhibited sensitivity of 0.98， specificity of 0.86， Matthews correlation coefficient of 0.84， and Youden index of 0.84. After the COVID-19 pandemic， these thresholds were 25.61%， 43.81%， 63.29%， 74.46%， and 17.82% respectively. At this point， the model demonstrates sensitivity of 0.86， specificity of 0.92， Matthews correlation coefficient of 0.78， and Youden index of 0.77. ConclusionMEM shows good applicability in estimating the epidemic and graded intensity thresholds of influenza during the winter and spring in Anhui province. Both the influenza epidemic threshold and graded intensity thresholds after the COVID-19 pandemic are higher than those before the pandemic.

ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.

To investigate the mechanism of Qitu Erzhi Decoction(QTEZ) in ameliorating chemotherapy-induced myelosuppression and the focus of its decomposed formulae on the effects of hematopoietic cells of the three lineages, respectively. Ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of QTEZ intestinal absorption liquid and obtain the target sites, which were intersected with chemotherapy-induced myelosuppression targets collected from several databases, including OMIM, and an interaction network was established based on network pharmacology for Gene Ontology(GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Hematopoietic stem cells of mice were taken after intraperitoneal injection of 5-fluorouracil for myelosuppression modeling and randomly divided into the model group, Qitu Erzhi group, Astragali Radix-Angelicae Sinensis Radix group, Ligustri Lucidi Fructus-Ecliptae Herba group, Psoraleae Fructus-Cuscutae Semen group, and positive drug group, which were given the corresponding traditional Chinese medicine intestinal absorption liquid and the positive drug granulocyte colony-stimulating factor, respectively. The normal hematopoietic stem cells were taken as the control group and were given the intervention of normal saline. The proliferation of hematopoietic progenitor cells of three lineages was observed by flow cytometry, and the cell cycle and colony formation assay were observed. Western blot was used to verify the effect of QTEZ on the pathway proteins including phosphoinositide 3-kinase(PI3K), phosphorylated PI3K(p-PI3K), protein kinase B(AKT), and phosphorylated AKT(p-AKT). RT-qPCR and Western blot were used to detect the effects of QTEZ on cell cycle-related targets such as CDK inhibitor 1(P21), cyclin D1(CCND1), and cyclin-dependent kinase 4(CDK4). The results showed that a total of 158 components were identified by QTEZ, and 375 component and disease intersecting targets were obtained, 21 core components and 40 core targets were obtained after constructing the network, and GO and KEGG enrichment showed signaling pathways such as PI3K/AKT. QTEZ and its decomposed formulae could promote the 5-fluorouracil-blocked cell cycle to resume operation, and all of them had different degrees of restoration effects on the set of colonies, among which QTEZ had the best restoration effect, and the Astragali Radix-Angelicae Sinensis Radix group had a focused effect on colony forming unit-erythrocyte. Western blot results indicated that there was no significant difference in the expression levels of pathway proteins among the groups. RT-qPCR and Western blot results showed that QTEZ could down-regulate P21 and up-regulate the protein and mRNA expression of CDK4 and CCND1. In conclusion, QTEZ and its decomposed formulas can exert a protective effect on hematopoietic stem cells with 5-fluorouracil-induced myelosuppression by promoting the normal operation of the cell cycle and colony formation, and the mechanism may be related to the down-regulation of the cell cycle-related targets of P21 and the up-regulation of CDK4 and CCND1. In addition, Astragali Radix-Angelicae Sinensis Radix can have a targeted protective effect on erythrocytes.
Animals ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Mice ; Fluorouracil/adverse effects* ; Male ; Antineoplastic Agents/adverse effects* ; Hematopoietic Stem Cells/cytology* ; Humans ; Signal Transduction/drug effects*

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Integrated medical curriculum is an important direction for the development of medical education. While integrated theoretical courses have been practiced for many years, integrated experiments are still in the exploratory stage. Taking the integrated experiments of medical microbiology and immunology in Xi'an Jiaotong University as an example, this article introduces the design concept, implementation details, effectiveness evaluation, improvements, and prospects of integrated experiments established based on clinical practice principles, so as to provide a reference for further optimization of integrated experiments in the future.

Objective To investigate the dosimetric effect of a biological optimization approach combining physical optimization with generalized equivalent uniform dose(gEUD)on hippocampus avoidance whole-brain radiotherapy(HA-WBRT).Methods A retrospective review was conducted of 20 patients with multiple brain metastases who underwent whole-brain radiotherapy at a certain hospital between May 2021 and December 2022.Two radiotherapy plans including plan_DV and plan_gEUD were designed for each patient by using Eclipse V15.6 planning system.Plan_DB used conven-tional dose-volume(DV)physical optimization,and plan_gEUD went through re-optimization with an Upper gEUD function applied to hippocampal region and hippocampal protection zone.Evaluation was carried out in accordance with RTOG 0933 guidance for the absolute values D2%,D98%and D50%received by 2%,98%,and 50%of the target volume in the planning target volume,conformity index(CI),homogeneity index(HI),gradient index(GI)and the dosimetric indexes of hippocampal region,hippocampal protection zone and other organs at risk(OARs).SPSS 26.0 software was used for statistical analysis.Results The two kinds of plans both had the target volume coverage meet the requirements of RTOG 0933 guidance.Plan_gEUD had the D98%,D2%and V105 of the planning target volume lower than those of plan_DV,with the differences being statistically significant(all P<0.05).The two kinds of plans had no significant differences in monitor unit,D50%and Dmax of PTV,HI,CI and GI(all P>0.05).Plan_gEUD had the Dmax and Dmean of hippocampal region and them of hippocampal pro-tection zone lower than those of plan_DV,and the optic nerve Dmax of plan_gEUD was higher than that of plan_DV,with the differences being statistically significant(all P<0.05).There were no statistically significant differences between the two kinds of plans in the Dmax of inner ear,optic chiasm,lens,and eyeball(all P>0.05).Conclusion Physical optimization in the HA-WBRT plan combined with gEUD optimization results in a greater dose reduction to the hippocampus while maintaining target coverage.

OBJECTIVE: This study aimed to identify high-risk areas for type 2 diabetes mellitus (T2DM) mortality to provide relevant evidence for interventions in emerging economies. METHODS: Empirical Bayesian Kriging and a discrete Poisson space-time scan statistic were applied to identify the spatiotemporal clusters of T2DM mortality. The relationships between economic factors, air pollutants, and the mortality risk of T2DM were assessed using regression analysis and the Poisson Log-linear Model. RESULTS: A coastal district in East Guangdong, China, had the highest risk (Relative Risk [RR] = 4.58, P < 0.01), followed by the 10 coastal districts/counties in West Guangdong, China (RR = 2.88, P < 0.01). The coastal county in the Pearl River Delta, China (RR = 2.24, P < 0.01), had the third-highest risk. The remaining risk areas were two coastal counties in East Guangdong, 16 districts/counties in the Pearl River Delta, and two counties in North Guangdong, China. Mortality due to T2DM was associated with gross domestic product per capita (GDP per capita). In pilot assessments, T2DM mortality was significantly associated with carbon monoxide. CONCLUSION High mortality from T2DM occurred in the coastal areas of East and West Guangdong, especially where the economy was progressing towards the upper middle-income level.
Diabetes Mellitus, Type 2/epidemiology* ; China/epidemiology* ; Humans ; Risk Factors ; Spatio-Temporal Analysis ; Air Pollutants/analysis* ; Socioeconomic Factors ; Bayes Theorem ; Female ; Male ; Middle Aged

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.