ObjectiveTo observe the clinical effectiveness and safety of Xiaozhong Zhitong Mixture （消肿止痛合剂） combined with antibiotic bone cement in the treatment of diabetic foot ulcer （DFU） with damp-heat obstructing syndrome. MethodsA total of 72 DFU patients with damp-heat obstructing syndrome were randomly assigned to treatment group （36 cases） and the control group （36 cases）. Both groups received standard treatment and topical antibiotic bone cement for ulcer wounds， while the treatment group received oral Xiaozhong Zhitong Mixture （50 ml per time， three times daily） in additionally. Both groups underwent daily wound dressing changes for 21 consecutive days. Ulcer healing rate， serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， malondialdehyde （MDA）， superoxide dismutase （SOD）， C-reactive protein （CRP）， and white blood cell （WBC） count were observed before and after treatment， and visual analog scale （VAS） scores for wound pain， traditional Chinese medicine （TCM） syndrome scores， and the DFU Healing Scale （DMIST scale） were also compared. Liver and kidney function were evaluated before and after treatment， and adverse events such as allergic reactions， worsening ulcer pain were recorded. ResultsTotally 35 patients in the treatment group and 33 in the control group were included in the final analysis. The ulcer healing rate in the treatment group was （87.93±9.34）%， significantly higher than （81.82±12.02）% in the control group （P = 0.035）. Compared to pre-treatment levels， both groups showed significant reductions in serum CRP， WBC， MDA， IL-1β， and TNF-α levels， with an increase in SOD level （P＜0.05）. TCM syndrome scores， VAS， and DMIST scores also significantly decreased in both groups （P＜0.05）， with greater improvements in the treatment group （P＜0.05）. No significant adverse reactions were observed in either group during treatment. ConclusionXiaozhong Zhitong Mixture combined with antibiotic bone cement has significant advantages in promoting DFU healing， reducing inflammatory response， and alleviating oxidative stress in DFU patients with damp-heat obstructing syndrome， with good safety for DFU patients with damp-heat obstructing syndrome.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Objective To investigate the epidemiological characteristics of cross-county imported dengue fever cases within Yunnan province in 2023, so as to provide insights into formulation of preventive and control measures for intra-provincial spread of dengue fever. Methods All data pertaining cross-county imported dengue fever cases within Yunnan Province in 2023 were collected, and the temporal, regional and population distributions of the cases were descriptively analyzed. Results A total of 1 664 intra-provincial cross-county imported dengue fever cases were reported in 95 counties (cities, districts) cross 16 profectures (cities) in Yunnan Province in 2023, accounting for 12.34% of total cases in the province. Cross-county imported dengue fever cases were predominantly reported during the period between August and October (1 516 cases, 91.11% of total cases), and peaked in September (659 cases), with a single-day peak on October 8 (36 cases). During the period from September 4 to 10, five counties (cities) with local dengue fever epidemics, including Jinghong City of Xishuangbanna Dai Autonomous Prefecture, Gengma Dai and Wa Autonomous County of Lincang City, Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, Mengla Coun ty of Xishuangbanna Dai Autonomous Prefecture, and Zhenkang County of Lincang City, exported 165 cross-county imported dengue fever cases to the rest of the province. Among the 1 644 intra-provincial cross-county imported dengue fever cases, the male to female ratio was 1.40∶1.00, and 1 329 cases were at ages of 15 to 55 years (79.87%), with farmers as the predominant occupation (886 cases, 53.25%). The top 5 counties (cities/districts) reporting the highest number of intra-provincial cross-county imported dengue fever cases included Simao District (266 cases) and Lancang Lahu Autonomous County (118 cases) of Pu’er City, Mengla County (91 cases) and Menghai County (91 cases) of Xishuangbanna Dai Autonomous Prefecture, and Mangshi City (73 cases) of Dehong Dai and Jingpo Autonomous Prefecture, which accounting for 38.40% of total imported cases. These intra-provincial cross-county imported dengue fever cases originated from 7 counties (cities/districts) in 4 prefectures (cities), including 1 261 cases (76.70%) from Jinghong City of Xishuangbanna Dai Autonomous Prefecture, 224 cases (13.63%) from Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, 103 cases (6.27%) from Gengma Dai and Wa Autonomous County of Lincang City, 31 cases (1.89%) from Mengla County of Xishuangbanna Dai Autonomous Prefecture, 30 cases (1.82%) from Zhenkang County of Lincang City, 10 cases (0.61%) from Cangyuan Wa Autonomous County of Lincang City, and 5 cases (0.30%) from Mohan-Boten Economic Cooperation Zone of Kunming City. In addition, local dengue fever epidemics following intra-provincial cross-county importation of dengue fevers cases in Simao District, Jinggu Dai and Yi Autonomous County, Mangshi City, Longchuan County, and Cangyuan Wa Autonomous County. Conclusions Farmers and students are high-risk populations for intra-provincial cross-county imported dengue fever cases in Yunnan Province, and health education pertaining personal protection against dengue fever should be strengthened among these high-risk populations by governments at all levels. There is a high risk of local out-break of dengue fever following continuous introduction of intra-provincial cross-county imported cases. Standardized management of intra-provincial cross-county imported dengue fever cases should be reinforced to reduce the risk of local epidemics.

OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E₂-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

Objective:To compare the differences in inhaled medication prescriptions among patients with chronic obstructive pulmonary disease (COPD) who visited the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD 2023) one year after its release and the previous year, and to analyze the impact of GOLD 2023 on physician inhaled medication prescriptions.Methods:This study was a cross-sectional study, with data sourced from the RealDTC study. The study subjects were chronic obstructive pulmonary disease patients who visited the respiratory and critical care departments of 13 hospitals in southern China from November 14, 2021 to November 15, 2023. According to the time of patient visits, they are divided into the following two groups: the group 1 year before the release of GOLD 2023 (November 14, 2021 to November 14, 2022), and the group 1 year after the release of GOLD 2023 (November 15, 2022 to November 15, 2023). We collected demographic characteristics, lung function, symptom scores, history of acute exacerbation in the past year, and inhaled medication prescriptions from patients. According to the symptom score of COPD patients in GOLD 2023 and their history of acute exacerbation in the past year, they were divided into three groups: A, B, and E. The treatment status of inhaled drugs in groups A, B, and E before and after the release of GOLD 2023 was compared.Results:There were statistically significant differences in COPD Assessment Test (CAT) scores, Modified Medical Research Council (mMRC) scores, and the number of acute exacerbations in the past year between patients with COPD before and after the release of GOLD 2023 (all P<0.05). Compared with the group one year before the release of GOLD 2023, the proportion of patients in the group one year after the release of GOLD 2023 using long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)+ long-acting β2-receptor agonists (LABA) was lower, while the proportion of patients using LABA+ LAMA and ICS+ LABA+ LAMA was higher (all P<0.05). There was no statistically significant difference ( P>0.05) in the proportion of patients in group A using LAMA between the year before and after the release of GOLD 2023. Compared to the year before the release of GOLD 2023, the proportion of patients in group A who prescribed ICS+ LABA was lower, while the proportion of using LABA+ LAMA and ICS+ LABA+ LAMA was higher (all P<0.05); The proportion of patients in group B who prescribed LAMA and ICS+ LABA was lower (all P<0.05), while the proportion of using LABA+ LAMA and ICS+ LABA+ LAMA was higher (all P<0.05); The proportion of patients in group E who prescribed LAMA and ICS+ LABA was lower (all P<0.05), while the proportion of using LABA+ LAMA and ICS+ LABA+ LAMA was higher (all P<0.05). Conclusions:After the release of GOLD 2023, the prescription of ICS+ LAMA in groups A, B, and E decreased, and the prescriptions of LABA+ LAMA and ICS+ LABA+ LAMA increased compared to before; However, in the real world, the compliance of physicians with GOLD 2023 is still not ideal.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas. Flap survival is closely related to a variety of factors including cellular autophagy, oxidative stress, inflammatory response, mesenchymal stem cells (MSCs) function, and vascular regeneration. Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair. Excessive oxidative stress and inflammatory responses pose a threat to flaps, affecting their survival and successful transplantation. Endothelial cells are involved in vascular regeneration through proliferation, migration, and production of angiogenic factors, and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action. The multiple roles played by cellular autophagy, oxidative stress, inflammatory response, MSCs function, and vascular regeneration in influencing postoperative flap survival are hereby elaborated. The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival, improve the success rate of flap surgery, reduce complications, and bring more hope for the recovery and quality of life of patients.