Ulcerative colitis is a chronic relapsing inflammatory bowel disease. Modern research indicates that immune dysregulation resulting from disruptions in circadian rhythm is closely associated with its pathogenesis. Both Western chronomedicine and traditional Chinese medicine（TCM）" treatment based on temporal factors" emphasize the temporal relationship between natural rhythms and human physiology and pathology. The " midnight-noon and ebb-flow " theory represents the concrete application and deepening of TCM " treatment based on temporal factors" within the realm of chronomedicine. This article correlates the onset time of ulcerative colitis with specific periods in the " midnight-noon and ebb-flow"theory：the Mao period（05：00-07：00），when the yangming large intestine meridian of hand is dominant； the Si period（09：00-11：00），when the taiyin spleen meridian of foot is dominant； and the You period（17：00-19：00），when the shaoyin kidney meridian of foot is dominant. According to this perspective，if the disease manifests during the Mao period，the pathogenesis is attributed to dampnessheat accumulation and disorder of qi and blood. Treatment should focus on clearing heat，resolving dampness，and harmonizing qi and blood，using modified formulas such as Shaoyao Decoction or Baitouweng Decoction. If it occurs during the Si period，the pathogenesis involves spleen deficiency with dampness obstruction and disharmony of qi and blood. Treatment should focus on strengthening the spleen，eliminating dampness，and restoring qi and blood，using modified formulas such as Huangya Decoction or Shenling Baizhu Powder. If it presents during the You period，the pathogenesis is characterized by fire failing to warm earth，and consumption resulting in qi and blood leakage. Treatment should focus on warming the kidney and spleen，and securing qi and blood，using modified formulas such as Sishen Pill or Tianhun Decoction. In addition to oral administration of Chinese herbal medicine，comprehensive therapies including acupuncture，herbal enemas，and acupoint application can provide novel insights for the clinical diagnosis and treatment of ulcerative colitis.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

[摘 要] 目的：探讨X连锁锌指蛋白（ZFX）通过Nectin-4表达影响食管鳞状细胞癌（ESCC）进展的分子机制及其对PI3K/AKT信号通路的激活作用。方法：收集2022年8月至2023年7月在南充市中心医院手术切除的30对ESCC组织及癌旁组织标本。采用人食管上皮细胞HET-1A及ESCC细胞KYSE-30、KYSE-150、KYSE-410、KYSE-510和TE-1。基于2018年至2019年收集的6例ESCC配对标本转录组测序数据筛选Nectin-4，通过TIMER2.0数据库、RT-qPCR和WB法、免疫组织化学（IHC）检测ESCC组织及细胞中Nectin-4的表达水平。采用shRNA技术在KYSE-410和KYSE-510细胞中敲低Nectin-4，通过CCK-8、克隆形成、划痕愈合及Transwell实验检测敲低Nectin-4对细胞增殖、迁移和侵袭能力的影响，采用WB法检测敲低Nectin-4对细胞PI3K/AKT通路及EMT相关蛋白表达水平的影响。通过生物信息学预测并结合双萤光素酶报告基因实验，鉴定并验证ZFX作为Nectin-4的上游转录调控因子。结果：综合分析显示，ESCC组织及细胞系中Nectin-4表达显著高于癌旁组织及HET-1A细胞（均P < 0.01）。功能研究表明，敲低Nectin-4显著抑制KYSE-410和KYSE-510细胞的增殖活性、克隆形成能力，以及迁移和侵袭能力（均P < 0.01）。机制方面，敲低Nectin-4时细胞中E-cadherin表达上调、N-cadherin下调（均P < 0.01），并抑制PI3K/AKT通路相关蛋白的磷酸化水平（P < 0.01）。结论： ZFX通过上调Nectin-4表达激活PI3K/AKT信号通路促进ESCC进展，为ESCC的治疗提供了潜在的新靶点。

ObjectiveThis study aims to investigate the therapeutic effects of Wenyang Xiaoyin Prescription （Linggui Zhugan Tang combined with Tingli Dazao Xiefei Tang） on a doxorubicin-induced mouse model of chronic heart failure （CHF）. The multi-targeting action mechanism of the therapy is revealed， based on the arginine vasopressin （AVP）-vasopressin V₂ receptor （V2R）-aquaporin 2 （AQP2） signaling pathway and nuclear transcription factor -κB （NF-κB） pathway mediated by the liver X receptor （LXR） in the heart， brain， and kidney tissue. MethodsCHF mouse models were established by using intraperitoneal injection of doxorubicin and subsequently divided into a blank control group， a model control group， Wenyang Xiaoyin Prescription groups （Linggui Zhugan decoction combined with Tingli Dazao Xiefei decoction） with various doses， a captopril group， and a combination group receiving both Wenyang Xiaoyin prescription （as before） and captopril. Cardiac function was assessed by using color Doppler echocardiography， while the levels of brain natriuretic peptide （BNP）， AVP， and the renin-angiotensin-aldosterone system （RAAS） in the serum were measured via enzyme-linked immunosorbent assay （ELISA）. Pathological changes and ventricular remodeling in ventricular tissues were evaluated through hematoxylin and eosin （HE） and Masson staining， and myocardial cell apoptosis of mice was assessed by using TdT-mediated dUTP Nick-End Labeling （TUNEL） staining. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to detect the protein and RNA expression levels of LXRα， nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS） in the cardiac tissue， LXRβ， AVP in the hypothalamus， and LXRβ， V2R， and AQP2 in the kidneys. Furthermore， immunohistochemistry was used to quantify AQP2-positive collecting ducts in renal tissues. ResultsThe Wenyang Xiaoyin prescription significantly enhanced cardiac function indicators in CHF mice， reducing levels of BNP， AVP， and RAAS in the serum. It also mitigated myocardial cell damage and fibrosis change. The Wenyang Xiaoyin prescription inhibited the expressions of NF-κB and its downstream targets TNF-α and iNOS and improved myocardial inflammatory response， cell apoptosis， and ventricular remodeling by upregulating the expression of LXRα in cardiac tissues. Concurrently， the Wenyang Xiaoyin prescription elevated LXRβ expression in the kidneys and hypothalamus while downregulating the expression levels of AVP， V2R， and AQP2， as well as water permeability in the collecting ducts， thereby alleviating cardiac load. ConclusionThe intervention of Wenyang Xiaoyin prescription demonstrates a significant therapeutic effect on CHF， and its role involves the multi-target effect mechanism of the AVP/V2R/AQP2 and NF-κB pathways mediated by the nuclear receptor LXR in the heart， brain， and kidney tissue.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Follicular Helper T Cells(TFH)are a specialized subset of CD4+T cells that predominantly lo-calize within lymphoid follicles.These cells play a crucial role in facilitating B cell proliferation,differentia-tion,and antibody production,thereby thereby serving as a pivotal component of the adaptive immune re-sponse against infections.Given the significant function of TFH cells in regulating humoral immunity,they have become a focal point in the research of infectious diseases and related vaccine development in recent years.This review summarizes the surface markers of T follicular helper(Tfh)cells,their differentiation reg-ulatory mechanisms,and the latest research progress of Tfh cells in SARS-CoV-2 infection and vaccine stud-ies.It aims to provide new theoretical foundations and research insights for optimizing the design of SARS-CoV-2 vaccines and enhancing the cross-protection ability against SARS-CoV-2 variants.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high global incidence rate, accounting for about 10.54% of all new cancer cases and posing a serious threat to human health. Due to significant individual variations in the efficacy of immunotherapy among NSCLC patients, it is necessary to identify accurate detection indicators to screen appropriate populations, monitor treatment efficacy, and assist in prognosis assessment. Programmed death-ligand 1 (PD-L1), as an immunosuppressive molecule expressed on the surface of tumor cells and various immune cell membranes, can serve as a "companion diagnostic" or "supplementary diagnostic" tool to guide clinical treatment decisions for metastatic NSCLC patients. Given that tumor tissue PD-L1 testing is an invasive procedure and its reliability is still under debate, the assessment of PD-L1 expression via liquid biopsies, such as circulating tumor cells, will play a significant role in predicting treatment response and prognosis in NSCLC patients.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

Objective To investigate the efficacy of Yiqi Wenyang Sanjie Decoction in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution,and to observe its effect on serum inflammatory factors and immune function.Methods From January 2020 to June 2024,a total of 106 patients with pulmonary ground glass nodules and yang-deficiency constitution admitted to the Department of Respiratory Medicine and Preventive Treatment of Disease Center of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected.The patients were randomly divided into control group and Chinese medicine group by random number table method,with 53 cases in each group.The patients in the control group were only given follow-up without any intervention,and the patients in the Chinese medicine group were treated with Yiqi Wenyang Sanjie Decoction for 3 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,maximum diameter of pulmonary ground glass nodules,serum levels of inflammatory factors of interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α),and levels of immune function indicators of peripheral blood CD3+,CD4+cell percentage and CD4+/CD8+ratio.After treatment,the efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the control group and 3 cases fell off from the Chinese medicine group.A total of 98 cases were eventually included,and 48 cases were in the control group and 50 cases were in the Chinese medicine group.(2)After 3 months of treatment,the total effective rate of the Chinese medicine group was 46.00%(23/50),and that of the control group was 10.42%(5/48).The intergroup comparison(tested by chi-square test)showed that the efficacy of the Chinese medicine group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group were lowered(P＜0.05),while the TCM syndrome score and the maximum diameter showed no obvious changes compared with those at enrollment(P＞0.05);the intergroup comparison showed that the reduction of TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum inflammatory factors of IL-6,IL-17A and TNF-α in the Chinese medicine group were significantly lowered compared with those at enrollment(P＜0.05),while there was no significant change in serum IL-6,IL-17A and TNF-α levels of the control group(P＞0.05);the intergroup comparison showed that the decrease of serum IL-6,IL-17A and TNF-α levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the percentage of T lymphocyte subset CD4+and the ratio of CD4+/CD8+in the Chinese medicine group were significantly increased compared with those at enrollment(P＜0.05),while there was no significant change in the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+of the control group and in the percentage of CD3+cells of the Chinese medicine group(P＞0.05).The intergroup comparison showed that the increase of CD4+percentage and CD4+/CD8+ratio in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(6)There were no obvious adverse reactions occurring in the Chinese medicine group during the treatment,showing relatively high safety.Conclusion Yiqi Wenyang Sanjie Decoction exerts certain effect in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution.It can effectively promote the reduction of nodules,relieve clinical symptoms,decrease serum levels of inflammatory factors,improve immune function,and has good safety.

Objective Accurate speed perception is crucial for tasks such as man-controlled rendezvous and docking,and teleoperation of space manipulator.Therefore,it is necessary to conduct in-orbit experiments to explore the influence of long-term spaceflight on human speed perception characteristics.Methods The Time-to-Collision(TTC)paradigm was selected to develop experimental software,using a tablet computer for stimulus presentation.Human speed perception characteristics were evaluated based on the subjects'keystroke response data on the keyboard.Through ground-based experiments,the usability and reliability of the paradigm were explored,and the gravity internal model effect was quantitatively analyzed.Through in-orbit experiments on space station tasks,the influence of long-term spaceflight on human speed perception characteristics was further investigated.Results Under the 1G environment on the ground,the TTC paradigm has a high test-retest reliability(r>0.8),and indicators such as average deviation rate and absolute value of average deviation rate show no practice effect.In addition,ground experiments found that compared to vertical upward movement,vertical downward movement is estimated to be faster(i.e.,keystroke time is advanced),showing the existence of the gravity internal model effect.In the microgravity environment of spaceflight,there are no significant differences in average deviation rate and absolute value of average deviation rate among three stages(pre-flight,in-flight,post-flight)and seven tests,indicating that no obvious changes in astronauts'speed perception ability were found at the existing test time points and paradigms.However,the gravity internal model effect(difference between vertical downward and vertical upward)showed a trend of fading in the early stage of astronauts entering orbit.Conclusion Based on the computer screen TTC estimation paradigm,no significant changes in human speed perception ability were found during long-term spaceflight,but microgravity may weaken the human brain's gravity internal model.