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.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

AIM: To observe the clinical outcomes of Phorcides analytic engine-assisted topography-guided personalized laser assisted in situ keratomileusis(LASIK)for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from corneal topography.METHODS: Retrospective clinical study. A total of 32 cases(42 eyes)with myopia and astigmatism that received corneal topography-guided personalized LASIK in the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to March 2021 were selected. The uncorrected distance visual acuity(UDVA), best corrected distance visual acuity(CDVA), refractive state and aberrations before and at 6 mo after surgery were recorded.RESULTS: There were 15 males and 17 females, with an age of 23.00(18.00, 29.25)years old; preoperative sphere was -5.75(-6.25, -4.00)D, and cylinder was -0.75(-1.38, -0.25)D. At 6 mo postoperatively, the UDVA exceeded the preoperative CDVA in 19 eyes(45%). The spherical equivalent(SEQ)of all eyes(100%)was -0.50 to +0.50 D at 6 mo postoperatively, and the postoperative SEQ of 23 eyes(55%)was -0.13 to +0.13 D. There were 33 eyes(79%)had a postoperative astigmatism ≤ 0.25 D, the target-induced astigmatism(TIA)was 0.94±0.96 D, and the surgically induced astigmatism(SIA)was 0.94±0.86 D, with no statistical significance between TIA and SIA(P>0.05). The astigmatism axial deviation ranged from -5° to +5° in 33 eyes(79%)at 6 mo postoperatively. Compared to pre-operation, the total higher-order aberrations and spherical aberrations within the central 6 mm diameter of the anterior corneal surface increased at 6 mo postoperatively(Z=-3.778, P<0.001; Z=-4.929, P<0.001); the postoperative coma aberrations had no change(Z=-1.763, P=0.078); the postoperative trefoil aberrations decreased(Z=-2.490, P=0.013). Compared to pre-operation, the Strehl ratio of the anterior corneal surface increased significantly at 6 mo after surgeries(t=-5.401, P=0.013).CONCLUSION: Using the Phorcides analytic engine to assist topography-guided personalized LASIK for the treatment of myopia and astigmatism in virgin eyes with the refractive astigmatism significantly deviating from topography-measured astigmatism can achieve good therapeutic effects. Postoperative UDVA exceeded preoperative CDVA in nearly half of the eyes, and the quality of postoperative corneal imaging was improved.

Objective:To investigate the overall drug resistance, drug resistance trend and distribution of drug resistance mutation sites in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients with antiviral therapy failure in Yunnan Province.Methods:The demographic data and genotype drug resistance of HIV/AIDS population with antiviral therapy failure in Yunnan Province from January 2021 to December 2023 were collected and analyzed by cross-sectional investigation. Statistical analyses were performed using chi-square test.Results:Among 15 159 HIV/AIDS patients, 12 215 cases tested positive by amplification. The circulating recombinant form (CRF) 08_BC was the predominant genetic subtype, accounting for 54.97%(6 714/12 215), followed by CRF01_AE (16.14%(1 972/12 215)) and CRF07_BC (14.48% (1 769/12 215)). When the viral load was ≥200 to <1 000 copies/mL, the incidence of drug resistance was 21.48%(99/461). When it was ≥1 000 to <10 000 copies/mL, the incidence was 51.29%(2 867/5 590). When it was ≥10 000 to <100 000 copies/mL, the incidence was 69.39% (3 979/5 734). When it was ≥100 000 copies/mL, the incidence was 81.86%(352/430). A total of 7 297 drug resistant cases were detected, with a drug resistance rate of 59.74% (7 297/12 215), thus the estimated drug resistance incidence rate among the antiviral treated population in Yunnan Province was 2.00% (7 297/364 238). From 2021 to 2023, the annual drug resistance rates among patients were 60.71%(2 554/4 207), 60.28%(1 671/2 772), and 58.67% (3 072/5 236), respectively, with no statistically significant difference ( χ2=4.47, P=0.107). Among the population with antiviral therapy failure, the drug resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) were 93.70%(6 837/7 297), 44.10%(3 218/7 297) and 5.15%(376/7 297), respectively. The mutation sites with the highest frequencies among the three classes of drugs including NRTI, NNRTI and PI were M184V/I (46.13%(2 123/4 602)), K103N/S (37.14%(2 648/7 129)), L33F (15.50%(82/529)) and M46I/L (15.50%(82/529)), respectively. Analysis of the degree of drug resistance showed that among NNRTI drugs, nevirapine (49.01%(5 987/12 215)) and efavirenz (48.00%(5 863/12 215)) had the highest drug resistance rates, followed by emtricitabine (23.59%(2 882/12 215)) and lamivudine (23.58%(2 881/12 215)) among NRTI drugs. Conclusions:Among HIV/AIDS patients with antiviral therapy failure in Yunnan Province from 2021 to 2023, CRF08_BC is the main genetic subtype. The drug resistance rate of patients increases with the increase of HIV-1 viral load. There is no significant change in the drug resistance rate from 2021 to 2023. NNRTI has the highest drug resistance rate, followed by NRTI, and PI has the lowest. The main mutation sites are M184V/I for NRTI, K103N/S for NNRTI, and M46I/L and L33F for PI. The drug resistance rates of nevirapine, efavirenz, emtricitabine and lamivudine are relatively high.

Objective:To analyze the practical experiences and challenges faced by nurses in community-based elderly care institutions in the management of insulin therapy for elderly patients with diabetes.Methods:This qualitative study employed purpose sampling to recruit nurses from two community-based elderly care institutions in Beijing from June to October 2023. Semi-structured interviews were conducted focusing on their experiences and challenges in insulin use for elderly patients with type 2 diabetes. All interviews were audio-recorded and transcribed into text. Framework analysis was used to analyze the interview data.Results:A total of 15 nurses participated in the interviews, all of whom were female with work experience ranging from 4 to 12 years. The analysis revealed three main themes and 2-3 subthemes under each theme. Theme 1 patients′ experiences with insulin injection: concerns about adverse reactions such as hypoglycemia, obesity, and injection pain; attention to insulin dosage, blood glucose levels, dietary management, and weight control. Theme 2 nurses′ practices and challenges in insulin management: communication and emotional support; trust-building between nurses and elderly patients; impact of insufficient human resources. Theme 3 nurses′ experiences with diabetes knowledge education and training: motivation for training; adaptation of training content, format and frequency to local conditions; implementation and significance of health education.Conclusions:The management of elderly people with diabetes in community-based elderly care institutions presents significant challenges. It is essential to provide personalized insulin management support, emotional support, and psychological counseling for elderly diabetic patients. Additionally, nurses require access to relevant diabetes knowledge education and training to enhance their ability of effective care.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To investigate effects of human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSCs-Exo)on bisphenol AF(BPAF)-induced oxidative damage and inflammatory factor release from endometrial stromal cells(hESCs).Methods:hESCs were divided into Control group,BPAF group(25 μmol/L BPAF treatment),BPAF+Exo group(25 μmol/L BPAF+hUCMSCs-Exo treatment),BPAF+Exo+LY group(25 μmol/L BPAF+hUCMSCs-Exo+10 μmol/L LY294002 treatment).Cell prolifera-tion was detected by MTT assay;apoptosis,intracellular ROS level,and mitochondrial membrane potential level were detected by flow cytometry;protein expressions of Bcl-2,Bax,Cleaved-caspase-3 and PI3K/AKT signaling pathway were detected by Western blot;mRNA expressions of inflammatory factors TNF-α,IL-6 and IL-1β were detected by RT-qPCR.Results:Compared with Control group,hESCs survival rate was gradually decreased(P<0.01),apoptosis rate was gradually increased with the increased concentration of BPAF(≥25 μmol/L).Compared with Control group,BPAF group showed increased ROS level,decreased mitochondrial membrane potential level,increased Bax and Cleaved-caspase-3 protein expressions,and decreased Bcl-2,p-PI3K and p-AKT protein expressions.Compared with BPAF group,cell survival rate of BPAF+Exo group was increased(P<0.01),ROS level decreased,mitochondrial membrane potential level increased,expressions of Bax and Cleaved-caspase-3 proteins decreased,and expressions of Bcl-2,p-PI3K and p-AKT increased.Compared with BPAF+Exo group,expressions of Bax and Cleaved-caspase-3 protein in cells of BPAF+Exo+LY group were increased,while expressions of Bcl-2,p-PI3K and p-AKT protein were decreased.Expressions of inflammatory factors TNF-α,IL-6 and IL-1β mRNA were significantly up-regulated in BPAF group compared with Control group(P<0.01),and expressions of inflammatory factors mRNA were significantly down-regulated in BPAF+Exo group compared with BPAF group(P<0.05).Conclu-sion:BPAF(≥25 μmol/L)inhibits proliferation of hESCs and promoted apoptosis.hUCMSCs-Exo inhibits BPAF-induced oxidative dam-age and inflammatory factors expressions in hESCs through PI3K/AKT signaling pathway.

Objective:To explore the mechanism of Hegu(LI4)point's effect on facial nerve from the perspective of modern medicine.Additionally,it seeks to investigate the specificity of LI4 effect on the face in comparison with other points,providing guidance for the clinical practice of acupuncture.Method:Twenty healthy subjects were enrolled in a crossover design(homozygous self before and after con-trol).The volunteers were randomly assigned to the LI4 group and the Quchi(LI11)group,with a two-week interval between the two groups was used as the washout period.The motor evoked potentials(MEPs)of the facial buccal muscles were compared before and after acupuncture in the LI4 and LI11 groups under various in-tensities of transcranial magnetic stimulation(TMS).The latency and amplitude of MEPs were measured at each intensity of TMS.At the end of the first trial,all volunteers entered the second trial after a two-week in-terval,with the grouping method of the second trial being the same as that of the first trial.The amplitude and latency of buccal muscle MEPs were recorded at eight time points(before needling,needling,leaving the needle in place for 3 minutes,electro-acupuncture,3 minutes after electro-acupuncture,switching off electro-acu-puncture,3 minutes after switching off electro-acupuncture and pulling out the needle)at a stimulation intensity.Result:The amplitude of buccal muscle MEPs increased significantly and the latency decreased significantly before and after the intervention in the LI4 and LI11 groups under TMS intensity of 1％to 25％.The differ-ence was statistically significant(P<0.001),and the rate of change in the amplitude of buccal muscle MEPs in the LI4 and the rate of change in the amplitude of buccal muscle MEPs in the LI4 group was significantly higher than that in the LI11 group(P<0.01).In test 2,the amplitude of buccal muscle MEPs in the LI4 group was lower than that in the LI11 group before acupuncture(P<0.01).The amplitude of buccal muscle MEPs was higher than that in the LI11group after electro-acupuncture,electro-acupuncture for 3 minutes,switching off electro-acupuncture,and switching off electro-acupuncture for 3 minutes(P<0.05).The latency of buccal muscle MEPs was lower than that of the LI4 group in the LI11group before,after,electro-acupunc-ture,electro-acupuncture,electro-acupuncture for 3 minutes,and switching off electro-acupuncture(P<0.05).There was no statistically significant difference between the two groups in other intervention phases(P>0.05).Conclusion:In the physiological state,needling both Hegu and Quchi increased buccal muscle excitability,and Hegu acupoints were more specific for increasing buccal muscle excitability compared with Quchi acu-points.