Fuchs endothelial corneal dystrophy(FECD)is a progressive dystrophic disease characterized by gradual damage to the corneal endothelium, ultimately leading to endothelial decompensation. The current standard treatment, corneal transplantation, has several limitations. Recent studies have shown that Rho-associated kinase(ROCK)inhibitors can promote cell proliferation by modulating the cyclin D and p27 signaling pathways. Additionally, ROCK inhibitors activate Rac1, which drives the actin-related protein complex(ARPC2)to enhance cell adhesion, and regulate processes such as membrane blebbing, nuclear disintegration, and apoptotic body formation, thereby inhibiting the apoptosis of corneal endothelial cells. These findings suggest that ROCK inhibitors may be a promising therapeutic approach for FECD. This review provides an overview of the pharmacological effects, basic research, clinical trials, and potential adverse reactions associated with ROCK inhibitors in the treatment of FECD, with the aim of developing compounds with stable efficacy and minimal side effects for the treatment of FECD in the near future.

BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Objective:To investigate the teaching activity based on an online radiological teaching case library that integrates various teaching models including problem-based learning (PBL), case-based learning (CBL), flipped classroom, and microclass, as well as its application effect in standardized residency training in department of radiology.Methods:A total of 65 physicians who completed standardized residency training in Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, from 2016 to 2022 were enrolled as subjects and were divided into control group with 32 physicians and experimental group with 33 physicians. The physicians in the control group received traditional teaching, and those in the experimental group received blended teaching with PBL, CBL, flipped classroom, and microclass based on a teaching case library. The two groups were compared in terms of the test scores of clinical thinking and decision making at the end of the course and their assessment and feedback for the teaching method. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:For the assessment of clinical thinking and decision making, compared with the control group, the experimental group had significantly higher score of objective essay questions (49.83±1.27 vs. 48.74±1.64, P<0.05), score of subjective essay questions (39.57±1.75 vs. 36.02±1.81, P<0.05), and total score (89.40±1.54 vs. 84.76±1.93, P<0.05). The experimental group had significantly better assessment and feedback for the teaching method than the control group ( P<0.05). Conclusions:For physicians participating in standardized residency training, the blended teaching model based on teaching case library that integrates PBL, CBL, flipped classroom, and microclass can effectively improve the test scores of clinical thinking and decision making, stimulate their learning initiative and participation enthusiasm in medical imaging, and enhance their comprehensive ability for clinical diagnosis.

Indole-3-propionic acid(3-IPA)is a metabolic product of tryptophan by gut microbiota,which plays an important role in maintaining host health and metabolic balance.3-IPA is suggested to influence host physical ac-tivities via enhancing the intestinal epithelial barrier,exerting anti-oxidative and anti-inflammatory effects,as well as im-mune modulation.Recent studies have indicated that deficiency of 3-IPA or gut microbiota imbalance is involved in the de-velopment of various metabolic disorders including obesity,diabetes and cardiovascular diseases,indicating 3-IPA is a po-tential marker in diagnosing these disorders.Furthermore,supplementation with 3-IPA or fecal microbiota transplantation(FMT)have been shown to effectively improve the metabolic diseases.This review summarizes the role and mechanism of 3-IPA in metabolic diseases,suggesting that strategies such as modifying dietary patterns or improving the microbial envi-ronment could provide new approaches for the prevention and treatment of these diseases.

Objective To explore the efficacy and safety of using a tourniquet in amputation for lower limb gangrene. Methods All patients underwent amputation for lower limb gangrene from January,2009 to June,2023 in Beijing Bo'ai Hospital were reviewed,involving 41 patients with a total of 44 limbs,and they were divided into non-tourniquet group(n=28)and tourniquet group(n=16)according to whether a tourniquet was used during surgery.The am-putation field clearness,surgical bleeding,incision healing,reoperation rate within 30 days post-operation,intra-operative blood pressure and heart rate,and operation time were compared. Results The amputation field was clearer in the tourniquet group(χ2=42.385,P＜0.001),with less bleeding(Z=-2.082,P＜0.05).No tourniquet-related local damages,such as nerve damage and skin injuries,was observed in the limbs using tourniquets.The incidence of grade A of incision healing was not significantly different(χ2=0.028,P=0.624). Conclusion Application of tourniquet can improve the amputation field clearness and reduce bleeding during amputation for lower limb gangrene,without affecting incision healing.

Objective To analyze the impact of different clinical and rehabilitation characteristics on the prognosis of diabetic foot amputees. Methods Related literatures were searched in CNKI,Wanfang Data,PubMed,Cochrane Library and Google Scholar from establishment to August,2024.The literatures were screened and extracted by two researchers independent-ly,the Newcastle-Ottawa Scale(NOS)and the evaluation criteria recommended by Agency for Healthcare Re-search and Quality(US)were used for quality evaluation,and literatures with above medium quality were includ-ed,and a systematic review was conducted. Results A total of 17 articles involving 9 239 subjects were included,in which three were Chinese,and 14 were English.The study designs were case-control study,cohort study and cross-sectional study.They mainly came from the fields of rehabilitation medicine,orthopedics,sports medicine and disability studies,and were published between 1998 to 2023.Clinical and rehabilitation characteristics related to the prognosis of diabetic foot amputees includ-ed amputation level,socioeconomic determinants(educational attainment,economic status,social participation,etc.),psychological states(anxiety,depression,etc.)and physiological factors(age,gender,pain,prosthetic limb usage,and ambulatory capacity,etc.).These different characteristics could affect the quality of life of diabetic foot amputees,and even lead to re-amputation or death. Conclusion Factors of amputation level,socioeconomic status,psychological status and physiological status are impor-tant for poor prognosis in diabetic foot amputees.Controlling the above factors can effectively reduce the re-am-putation rate and mortality,and improve the quality of life in diabetic foot amputees,thus improving their progno-sis,and promoting functional rehabilitation.

Zuoguiwan， one of the classic formulas of traditional Chinese medicine （TCM）， has the effects of nourishing genuine Yin， supplementing essence， and replenishing marrow， and it is widely used in the clinical treatment of diseases caused by congenital essence deficiency. This article systematically reviewed the ancient books involving congenital deficiency and the modern research reports on the treatment of congenital deficiency with Zuoguiwan. From the formulation principle of Zuoguiwan and the TCM concept of congenital deficiency， this article discussed the theoretical basis of treating congenital deficiency with Zuoguiwan based on the modern research results. Ancient physicians have discovered that the deficiency of parents can lead to abnormal physical development and weakness of the offspring. ZHANG Jingyue divided congenital essence Qi into genuine Yin and primordial Yang and formulated Zuoguiwan based on the principle of Yin-Yang mutual assistance for supplementing congenital genuine Yin. Experimental studies have shown that Zuoguiwan can up-regulate the expression of connexin 43 （Cx43） protein and improve gap junction intercellular communication （GJIC） function to promote osteogenic differentiation and maturation of bone marrow mesenchymal stem cells and ameliorate abnormal bone development caused by congenital essence deficiency. Zuoguiwan can enhance the expression and activity of Reelin to ameliorate abnormal brain development. It can upregulate the expression of Cx43 protein to intervene in the phosphatidylinositol 3 kinase/protein kinase B （PI3K/Akt） pathway， thus repairing the reproductive functions. Zuiguiwan can promote the development and maturation of T cells and activate the Wnt/β-catenin signaling pathway in the thymus to improve immune functions. In addition， it can promote the expression of β-catenin and inhibit the expression of microtubule-associated proteins 1 light chain 3 （LC3） to attenuate skin dysfunctions. Moreover， Zuoguiwan can guide the differentiation of stem cells via the correlation between essence and vitality in TCM. Zuoguiwan has demonstrated significant therapeutic effects on some diseases in the pediatric， andrological， gynecological， geriatric， internal medicine， orthopedic and skin disease departments. On the basis of the results of experiments and clinical applications， this paper analyzes the specific connotation of congenital deficiency proposes that congenital deficiency should be subdivided into the four aspects of essence， Qi， Yin， and Yang. Congenital essence deficiency as the deficiency of genuine Yin can lead to deficiency of kidney essence in the offspring and dysfunction of kidney storing essence. Pharmacological studies have discovered that Cuscutae Semen， Lycii Fructus， and Achyranthis Bidentatae Radix in Zuoguiwan contain active components such as quercetin and kaempferol， which act on the targets such as recombinant prostaglandin endoperoxide synthase 2 （PTGS2）， interleukin-6 （IL-6）， mitogen-activated protein kinases （MAPK14）， tumor necrosis factor （TNF）， TP53， Vascular permeability factor A （VEGFA）， and albumin （ALB） to play a role in reproductive system development and hormone responses. Zuoguiwan has unique advantages over Liuwei Dihuangwan in nourishing congenital genuine Yin in the kidney and can achieve better therapeutic effects on the syndromes and diseases caused by congenital essence deficiency. This review is expected to enrich the knowledge about the efficacy and clinical application of Zuoguiwan， provide new perspectives and methods for the prevention and treatment of congenital deficiency and congenital essence deficiency， and give insights into the application of Zuoguiwan in modern healthcare， especially in the nurturing of offspring.

Objective To investigate the relationship between serum fatty acid binding protein(FABP)1,FABP2 and diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM)and its diagnostic value.Methods A total of 170 patients with T2DM diagnosed and treated in this hospital from January 2020 to December 2022 were selected as the research objects.According to urinary albumin to creatinine ratio(UACR),they were divided into non-DKD group(UACR<30 mg/g,72 cases)and DKD group(UACR≥30 mg/g,98 cases).A total of 60 healthy people in the same hospital during the same period were selected as the control group.Pearson correlation analysis was used to analyze the correlation between serum FABP1,FABP2 and renal function related indicators.Multivariate Logistic regression was used to analyze the influencing fac-tors of DKD.Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of serum FABP1 and FABP2 for DKD.Results The DKD group had significantly higher serum levels of FABP1 and FABP2 than the non-DKD group and the control group(P<0.05),and the non-DKD group had significantly higher serum levels of FABP1 and FABP2 than the control group(P<0.05).Compared with the non-DKD group,the DKD group had a significantly lower eGFR and significantly higher UACR,serum creatinine,blood urea nitrogen,and serum uric acid levels(P<0.05).Serum FABP1 and FABP2 levels were positively correla-ted with UACR,serum creatinine,blood urea nitrogen,and negatively correlated with eGFR(P<0.05).In-creased serum FABP1 and FABP2 levels were independent risk factors for DKD.The serum FABP1,FABP2 joint detection diagnosis efficiency was better than that of serum FABP1,FABP2 detection alone(Z=4.712,4.363,P=0.001,0.002).Conclusion The serum levels of FABP1 and FABP2 are increased in patients with DKD,and they are related to the degree of renal function damage,which are independent risk factors for the occurrence of DKD in patients with T2DM.The combined detection of FABP1 and FABP2 has a high diagnos-tic efficiency for the occurrence of DKD in patients with T2DM.

Objective : To evaluate the effect of Arthroscopic Treatment of Popliteal Cyst through the modified double posteromedial portal． Methods : A total of 210 patients who diagnosed with popliteal cyst between April 2019 and June 2021 were chosen．62 patients underwent surgical treatment，include open excision and arthroscopic surgery．At the same time，31 patients with conservative treatment were included as conservative treatment group．The Visual Analogue Score( VAS score) ，Lysholm knee function score，and Knee Society Score ( KSS) scores were as- sessed before and 3 months after the operation. Results : In the open excision group，preoperative VAS score was 3. 69 ± 0. 93，Lysholm score was 63. 75 ± 4. 76，KSS score was 60. 87 ± 5. 85，and postoperative VAS score was 2. 04 ± 1. 04，Lysholm score was 76. 81 ± 6. 35，KSS score was 70. 42 ± 4. 87．In the arthroscopic surgery group，preoper- ative VAS score was 3. 81 ± 0. 84，Lysholm score was 62. 84 ± 4. 85，KSS score was 58. 95 ± 4. 79，and postoperative VAS score was 1. 47 ± 0. 85，Lysholm score was 82. 35 ± 7. 34，KSS score was 78. 52 ± 5. 67．In conservative treatment group，preoperative VAS score was 3. 92 ± 1. 02，Lysholm score was 61. 39 ± 3. 92，KSS score was 62. 42 ± 6. 78，and postoperative VAS score was 3. 94 ± 1. 14，Lysholm score was 61. 85 ± 7. 48，KSS score was 60. 52 ± 6. 37．Significant improvement was observed in all the measurements after the operation compared to before the oper- ation(P ＜0. 001 ) ．Compared with the open excision group，the arthroscopic surgery group improved better (P < 0. 05) ． Conclusion Arthroscopy through the modified double posteromedial portal in the treatment of popliteal cyst has satisfactory results.