ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

ObjectiveTo evaluate the effect of Ningying Formula （宁瘿方） combined with low-dose antithyroid drugs （ATDs） on the relapse risk for patients with Graves' hyperthyroidism （GH） during the remission phase， and to analyze the related factors between GH relapse and thyrotropin receptor antibody （TRAb） negativity， so as to provide evidence for the standardized management of GH in remission stage. MethodsA single-center retrospective cohort study was conducted， including 269 GH patients in the remission stage. After propensity score matching （PSM）， 102 matched pairs （204 patients） were established. The control group received low-dose ATDs as maintenance therapy， while the exposure group received the core Ningying Formula in addition to low-dose ATDs. The primary outcome was the GH recurrence rate； the secondary outcome was the thyrotropin receptor antibody （TRAb） negativity rate （TRAb＜1.75 IU/L）. Safety outcomes included treatment-related adverse events. Differences between groups were assessed using Cox regression models and Kaplan-Meier curves， with sensitivity analysis performed using inverse probability of treatment weighting （IPTW）. ResultsThe median follow-up in the matched cohort was 28.07 months. Regarding the GH recurrence outcome， the recurrence rate in the exposure group （18/102， 17.6%） was significantly lower than that in the control group （31/102， 30.4%； χ²=4.539， P=0.033）； regarding the TRAb negativity outcome， the TRAb negativity rate in the exposure group （50/102， 49.0%） was significantly higher than that in the control group （23/102， 22.5%； χ²=15.551， P＜0.001）. Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence ［HR=0.324， 95%CI（0.170， 0.617）， P＜0.001］. Male ［HR=2.209， 95%CI（1.079， 4.520）， P=0.030］， higher initial TRAb level ［per 1 IU/L increase： HR=1.033， 95%CI（1.003， 1.064）， P=0.032］， and larger thyroid volume ［per 1 ml increase： HR=1.045， 95%CI（1.003， 1.088）， P=0.035］ were identified as independent risk factors for recurrence； multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity ［HR=1.826， 95%CI（1.091， 3.056）， P=0.022］， while a higher initial TRAb level was associated with a lower probability of negativity ［HR=0.974， 95%CI（0.950， 0.998）， P=0.032］. Survival analysis showed significant differences in relapse rate between groups （Log-Rank P=0.003） and in TRAb outcomes （Log-Rank P=0.034）. The incidence of treatment-related adverse events was similar between groups （P=0.757）. The IPTW sensitivity analysis was consistent with the primary analysis， indicating robust results. ConclusionThe Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage， without increasing common adverse events， making it an optional strategy for reducing relapse risk during remission. Male gender， higher baseline TRAb level， and larger thyroid volume indicate a higher risk of recurrence， warranting focused follow-up and stratified management.

ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Microbial infections are a prevalent challenge in the prevention and treatment of oral diseases. Antibiotic therapy faces clinical limitations due to its single-target mechanism and tendency to induce resistance with repeated use, necessitating novel antibacterial strategies. Stimuli-responsive antibacterial materials, whose antimicrobial activity can be modulated by external stimuli, offer advantages such as remote controllability, potential for localized precision treatment, and a reduced risk of inducing resistance. Among these materials, mechanical force-triggered piezoelectric materials exhibit significant antibacterial activity in the biomedical field owing to their unique piezoelectric effect, excellent stability, and good biocompatibility. Research has shown that piezoelectric materials can convert mechanical energy into electrical energy in response to external forces, which enables antibacterial effects without requiring an external power source. The underlying mechanisms primarily include direct electric field effects, generation of reactive oxygen species, and immune modulation. Preliminary applications in treating oral infections (e.g., dental caries, periodontitis, and peri-implantitis) have confirmed their stability and biocompatibility, establishing a foundation for clinical translation. However, long-term efficacy and biosafety in the complex oral microenvironment require further validation. Future research should focus on optimizing material preparation protocols to enhance antibacterial efficacy and stability, further investigating the underlying antimicrobial mechanisms, and systematically evaluating their therapeutic outcomes and safety profiles across various types of oral infections. This review summarizes the antibacterial effects, mechanisms, stability, safety, and research progress of piezoelectric materials in the stomatologic field, aiming to provide new insights for further research and application in this area.

Objective: To understand the prevalence of myopia among primary and secondary school students in minority areas of Yunnan Province, and to explore the influence of outdoor activities and short-distance use of eyes, so as to provide a basis for early myopia intervention. Methods: In October 2020, the survey was conducted among 1 782 primary and secondary school students in three cities of Yunnan through a multi stage random cluster sampling method. All subjects underwent a questionnaire survey and the visual acuity examination at baseline. The first follow-up was conducted in October 2021 to obtain 1 691 valid samples, and the second follow-up was conducted in May 2023 to obtain 1 367 valid samples. Factors associated with myopia among primary and secondary school students were explored by using generalized estimating equations. Results: The prevalence rates of myopia in 2020, 2021 and 2023 were 52.64%, 61.62% and 69.35%, respectively, showing an increasing trend ( χ 2 trend =91.77, P <0.05). The results of multivariate regression analysis on the generalized estimation equations showed that age at baseline ( OR =1.31), girls ( OR =1.76), Hani ethnicity ( OR =0.75), Bai ethnicity ( OR =0.69), parental myopia ( OR =1.97-2.29), parents often reducing children s exercise time for homework or tutoring ( OR =1.35), less than 1 time or 2-3 times of ball sports per week ( OR =1.27, 1.20 ), reading and writing in the classroom during the break ( OR =1.27), reading in direct sunlight occasionally ( OR =1.20), using only desk lamp for writing at home ( OR =0.71), more than 1 hours of short-distance eye use for a break once ( OR =1.23) were associated with myopia among primary and secondary school students ( P <0.05). Conclusions Outdoor activities and short-distance use of eye among primary and middle school students in minority areas in Yunnan province are suboptimal. Enhancing the related environmental and behavioral factors can effectively mitigate the occurrence and progression of myopia.

Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.