ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg^-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.

The development of primary-level prevention and control of osteoporosis in China has started relatively late, and the effectiveness of standardized prevention and control at the grassroots level requires further improvement. Observational and cross-sectional studies focused on postmenopausal women with osteoporosis vertebral fracture in community settings reveal issues such as low screening rates, low awareness, low diagnosis rates, and low treatment rates. These findings highlight the importance of addressing osteoporosis prevention and treatment at the community level. In response, 15 experts from across the country engaged in an intensive discussion on how to enhance the basic management of primary osteoporosis and promote multilevel referral. This article summarizes the discussion.

Sepsis is a prevalent form of acute and critical illness encountered in intensive care unit (ICU), characterized by a high mortality and cognitive impairments among survivors. The pathogenesis of sepsis primarily involves immune dysfunction and excessive oxidative stress. Consequently, immune modulation, along with anti-inflammatory and antioxidant strategies, has emerged as a focal point in the treatment of sepsis. Recent studies have highlighted the potential of B vitamins to modulate immune cell activity while exhibiting anti-inflammatory and antioxidant properties, thereby garnering significant interest regarding their therapeutic efficacy in sepsis management. Notably, vitamin B2 and vitamin B9 are recognized for their roles in regulating immune cells and facilitating immune modulation. Vitamins B1, B2, B6, and B12 demonstrate notable anti-inflammatory and antioxidant effects. Specifically, vitamin B1 exerts its antioxidant influence through the regulation of the tricarboxylic acid cycle while mitigating inflammation by modulating inflammatory factor levels in septic patients—an application that has been integrated into clinical practice. The anti-inflammatory action of vitamin B2 is achieved through the regulation of inflammatory mediators in septic patients alongside reducing inflammasome activation within macrophages. Vitamin B6 contributes to both anti-inflammatory responses and antioxidative defense by scavenging free radicals and enhancing the production of antioxidant enzymes. Furthermore, vitamins B1, B6, B9, and B14 have shown promise in improving neurocognitive function among individuals suffering from sepsis. This article reviews the immunomodulatory functions as well as the anti-inflammatory and antioxidative effects associated with various B vitamins while exploring their applications within sepsis treatment to propose novel therapeutic avenues.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To explore the risk factors related to acute rejection (AR) after pediatric kidney transplantation (KT).Methods:Retrospective analysis was performed for 189 pediatric KT recipients from September 2011 to August 2022.They were divided into two groups of AR (n=33) and non-AR (n=156).Univariate and multivariate Logistic regression analyses were performed for identifying potential risk factors of AR.And the effects of AR on graft function and survival were also examined.Results:During follow-ups, a total of 33(17.5%) patients developed AR with a 1-year cumulative incidence of AR of 16.9%(32/189).Univariate analysis revealed that median time on dialysis was longer in AR group than that in non-AR group (19 vs. 11 months, P=0.034).Median age of donors (12 vs. 24 months, P=0.033), median weight of donors (9.5 vs. 12 kg, P=0.025) and median donor/recipient body weight ratio (0.36 vs. 0.50, P=0.005) were lower in AR group than those in non-AR group.And the proportion of subtherapeutic tacrolimus (TAC) trough level was higher in AR group than that in non-AR group (45.5% vs. 21.2%, P=0.004).Multivariate regression analysis indicated that subtherapeutic TAC trough level was an independent risk factor for AR ( OR=2.977, 95% CI: 1.314-6.743, P=0.009).At the last follow-up, serum creatinine and eGFR were (78.4±24.3) vs. (74.6±24.7) μmol/L and (85.3±26.3) vs. (89.5±24.2) ml·min -1·1.73 m -2 in AR and non-AR groups respectively.There were no significant differences.1/5-year patient survival rate was both 97% in AR group and both 99.4% in non-AR group; 1/5-year graft survival rate both 90.9% in AR group and was 98.1% and 97.4% in non-AR group.No significant inter-group differences existed in patient and graft survival. Conclusions:Although an occurrence of early AR does not negatively impact graft outcomes, the incidence of AR remains high after pediatric KT.Therefore prompt diagnosis and treatment of AR should be strengthened.

Limb replantation and transplantation is the optimal treatment for traumatic limb amputation. Safe and effective limb preservation is the key factor to determine the success of limb replantation and transplantation. Currently, static cold storage is the gold standard of limb preservation. However, the preservation time is short, which may no longer meet clinical requirements. With rapid development of organ preservation in recent years, novel preservation technologies, such as ultra-low temperature preservation, supercooling preservation and mechanical perfusion preservation, have successively emerged. However, at present, these techniques are primarily applied to the preservation of solid organs rather than composite tissue allografts with blood vessels including limbs. In this article, research status and progress on the application of static cold storage and mechanical perfusion preservation in limb preservation were reviewed, aiming to provide reference for clinical application of limb preservation technology and promote the development of limb replantation and transplantation.

Bacillus spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
Anti-Bacterial Agents ; Anti-Infective Agents/pharmacology* ; Bacillus ; Bacillus subtilis ; Lipopeptides/pharmacology* ; Peptides, Cyclic/pharmacology*