Dry eye disease(DED)is a common ocular surface disorder worldwide, primarily characterized by a loss of homeostasis of the tear film, and frequently associated with meibomian gland dysfunction(MGD), decreased tear film stability, ocular discomfort, and visual impairment. In recent years, factors such as the widespread use of digital devices,the aging population, and environmental changes have contributed to a significant increase in its global prevalence, making it a major public health concern. Red light therapy(RLT), also known as low-level laser therapy(LLLT)or photobiomodulation(PBM), is a non-invasive treatment that utilizes low-energy red or near-infrared light to irradiate tissues. It exerts photobiomodulatory effects to promote cellular repair and functional recovery. This therapy has demonstrated considerable potential in treating various ocular conditions. Its broader clinical application could improve therapeutic outcomes, alleviate patient discomfort and financial burden, and reduce the consumption of healthcare resources, thereby yielding significant socio-economic benefits. This paper systematically reviews the multifaceted mechanisms and application prospects of RLT in managing DED, including its anti-inflammatory effects, improvement of meibomian gland function, promotion of conjunctival goblet cell repair, and alleviation of visual fatigue, aiming to provide a theoretical foundation and practical reference for its clinical adoption.

Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Renal fibrosis represents the pivotal pathological process driving the progression of chronic kidney disease (CKD) towards end-stage renal disease. Its core manifestations include chronic inflammation, excessive deposition of extracellular matrix (ECM), and tubulointerstitial injury resulting in functional deterioration. Emerging research on the molecular mechanisms underlying renal fibrosis has established that, beyond the canonical Smad-dependent pathway, transforming growth factor-β1 (TGF-β1) also modulates fibrogenesis through non-canonical signaling pathways, notably the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascades. These non-canonical pathways engage in crosstalk with the canonical Smad pathway, synergistically regulating key processes such as ECM metabolism, inflammatory responses, and epithelial-mesenchymal transition (EMT), thereby collectively orchestrating the initiation and progression of renal fibrosis. Notably, various active components derived from traditional Chinese medicine have demonstrated anti-fibrotic efficacy by modulating these pathways, highlighting their promising multi-target therapeutic potential. This review aims to systematically summarize recent advances in understanding the roles of TGF-β1-mediated MAPK and PI3K/Akt non-canonical signaling pathways in renal fibrosis and to discuss potential therapeutic strategies targeting these pathways.

[Objective] To explore the feasibility of using whole blood as a source of NK cells for allogeneic CAR NK cell therapy and activated NK cell reinfusion therapy, and initially construct a technical system for the separation and purification of NK cells from whole blood. [Methods] All peripheral blood mononuclear cells (PBMCs) were enriched from 400 mL of whole blood by manual separation and machine separation, respectively. The erythrocyte loss rate, PBMCs number, NK cell purity of the two methods were compared. NK cells were sorted from PBMCs by three separation and enrichment methods as immunomagnetic bead negative selection method, platelet lysate culture expansion and PERCOLL density gradient separation method, and the purity and yield of NK cells, the activity of NK cells and the tumor-killing ability of the three separation and enrichment methods were compared. [Results] The proportion of NK cells in the lymphocyte population was higher in the manual separation method than in the machine separation method[(13.16±5.16)% vs (8.56±3.92)%, P<0.05]; the number PBMCs was lower in the manual separation method than in the machine separation method[(4.09±1.80)×10⁸vs (6.49±2.16)×10⁸, P<0.05], and there was no difference in the red blood cell loss between the two methods (P>0.05). The purity of NK cells isolated and enriched from PBMCs by manual separation method using immunomagnetic was (96.77±2.31)%; the yield was (56.27±10.47)%; the inhibition of tumor proliferation was (38.67±14.05)%; and the tumor killing rate was (19.90±8.05)%. The purity of NK cells isolated and enriched from PBMCs by manual separation method using platelet lysis culture expansion method was the highest at day 7, which was (54.84±15.80)%; the cell expansion multiple could reach 16.92±6.28 at day 7; the in vitro tumor killing rate of NK cells was (15.83±5.5)%; the tumor inhibition rate was (44.33±13.5)%; and there was no difference in the toxicity and activity of NK cells between the two methods (P>0.05). The purity of NK cells isolated and enriched by PERCOLL density gradient separation method was (15.83±5.82)%, and the yield was (14±6.25)%, which was significantly lower than the other two methods. [Conclusion] PBMCs isolated from whole blood by manual separation and NK cells enriched by negative selection with immunomagnetic beads have the potential to provide NK cell materials for CAR-NK cell therapy, and NK cells enriched by platelet lysate-conditioned medium have the potential to provide NK cells for large-scale NK cell activation reinfusion therapy.

Objective To conduct a unique and pioneering molecular epidemiological investigation of a case of Eurasian avian-like H1N1 swine influenza identified in Yunnan Province in 2022(the fourth such case in the province)and to understand its genetic characteristics so as to reveal its potential impact on human health.Methods Real-time fluorescent quantitative PCR detection technology was used for the nucleic acid testing of the case's pharyngeal swab samples,close contacts,and environmental samples from the living area.Positive samples were subjected to virus isolation using MDCK cells.Cell cultures were authenticated using erythrocyte agglutination assay with guinea pig blood and real-time fluorescence quantitative RT-PCR.Whole genome sequencing was performed using the Illumina MiseqNext-generation sequencing platform,and a phylogenetic tree was constructed using MEGA 7.0 software to analyze the genetic molecular characteristics.Results The first G5 genotype Eurasian avian-like H1N1 swine influenza virus in Yunnan Province was successfully isolated,and the whole genome sequence of the virus was obtained.This virus possessed the molecular characteristics associated with increased adaptability,virulence,or transmissibility in mammals and had a nucleotide consistency of 99.2％～99.7％with a porcine strain isolated in Jiangsu province.These findings underscored the potential threat this virus poses to human health.Conclusion The study underscores the importance of further monitoring swine influenza in preventing new influenza virus subtypes that can infect humans.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

ObjectiveTo investigate the correlation between iron metabolism parameters and various syndrome types of unstable angina pectoris （UAP）. MethodsA cross-sectional study was conducted from October 2021 to October 2023， encompassing 213 patients diagnosed with UAP at Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences. Additionally， 30 healthy individuals were selected as control cases. Single-factor analysis was used to investigate the differences in clinical data among different Traditional Chinese Medicine （TCM） syndrome types of UAP and their correlation with iron metabolism indices. The study conducted a comparative analysis of the aforementioned clinical data among patients with and without heat-toxic and blood-stasis syndrome. Logistic regression was used to analyze the correlation between TCM syndrome types and related factors. The receiver operator characteristic （ROC） curve was employed to assess the predictive value of iron metabolism indices， along with their sensitivity and specificity. ResultsCompared to those in the control group， serum iron （SI） and serum ferritin （SF） levels were significantly increased in the UAP group （P<0.01）， while transferrin （TRF） and total iron binding capacity （TIBC） levels were decreased （P<0.01）. However， there was no significant difference in unsaturated iron binding capacity （UIBC）. Multivariate binary Logistic regression analysis identified apolipoprotein A1 （ApoA1）， homocysteine （HCY）， high-sensitivity C-reactive protein （hs-CRP）， and SF as independent influencing factors for the UAP patients （P<0.05， P<0.01）. Additionally， statistically significant differences were observed in SI， SF， TRF， and TIBC among 213 patients with different TCM types （P<0.01）. Patients with heat-toxic and blood-stasis syndrome had higher SI and SF values than those without the syndrome （P<0.01）， while their TIBC and TRF values were lower （P<0.01）. Multivariate binary logistic regression analysis showed that SI and LDL-C levels were closely associated with the differentiation of heat-toxic and blood-stasis syndrome. ConclusionUAP patients often experience iron metabolism disorders， and the heat-toxic and blood-stasis syndrome are significantly correlated with iron metabolism parameters. The SI and LDL-C levels have high specificity and sensitivity in diagnosing heat-toxic and blood-stasis syndrome.

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

The incidence of less common tumors is intermediate between rare tumors and high-prevalence tumors,while these less common tumors such as biliary tract cancers generate a significant regional health burden. The overall incidence of less common tumors is relatively low, and thus their clinical epidemiological studies face challenges such as recruitment difficulties,poor representation,and low standardization. Surgical center-based disease-specific cohorts have the advantages of case concentration,complete samples,and well-developed data,which are uniquely valuable in clinical epidemiological studies. Taking the disease-specific cohort of biliary tract cancers as an example,the authors combed through the relevant references and summarized the thinking in the practice of constructing disease-specific cohorts of less common tumors based on surgical centers. The architecture of the disease-specific cohort construction has been generalized as follows: the hardware includes a database, a biobank, and a platform of information synchronization, and the software follows the design principle of “high cohesion and low coupling”. The authors also recommend an orderly expansion of study size and implementation of quality control through all segments of cohort construction, and hope that these reflections could provide a reference for similar disease-specific cohorts.