Autoimmune uveitis is a blinding intraocular inflammation primarily caused by immune dysregulation mediated by CD4+ T cells. CD4+ T cells differentiate into various functional subsets, including Th1, Th2, Th17, and Treg cells. These subsets participate in immune responses and mediate the initiation and resolution of inflammation by secreting different cytokines. This article primarily focuses on the functional characteristics and interplay network of Th1/Th2 and Th17/Treg cells, along with the specific effects of their key secreted cytokines(e.g., IFN-γ, TNF-α, IL-17, IL-10, TGF-β)in driving or suppressing ocular inflammation. The goal is to clarify the fundamental pathogenesis of this disease from the perspective of immune balance. Furthermore, this work explores potential therapeutic targets based on restoring the balance between Th1/Th2 and Th17/Treg, such as modulating the differentiation of specific subsets, blocking key pro-inflammatory cytokines, or enhancing anti-inflammatory functions. This investigation aims to provide a scientific rationale and guidance for optimizing existing diagnostic and therapeutic strategies, as well as developing new immunotherapies(e.g., biological agents, cell therapies).

Objective To investigate the seroprevalence of Toxoplasma gondii infections among patients with hematological diseases, so as to provide insights into improving the prognosis and quality of life among patients with hematological diseases. Methods A total of 240 patients with hematological diseases (including 170 patients with hematological tumors and 70 patients with non-tumor hematological diseases) admitted to The Affiliated Hospital of Putian University during the period from January 1, 2021 through October 10, 2023 and 500 healthy volunteers in the hospital during the same period were enrolled. Subjects’ demographics and serum samples were collected, and serum specific IgG and IgM antibodies against T. gondii were detected using the chemiluminescence assay, with any of a positive IgG or IgM antibody defined as a positive T. gondii infection. The seroprevalence of specific IgG and IgM antibodies against T. gondii was compared between patients with hematological diseases and healthy volunteers. Results The mean age (F = 2.034, P > 0.05) and gender distribution (χ² = 0.462, P > 0.05) were comparable among patients with hematological tumors, patients with non-tumor hematological diseases and healthy volunteers, and there was no significant difference in the proportion of history of cat or dog contacts between patients with hematological diseases and healthy volunteers (χ² = 0, P > 0.05). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological diseases than among healthy volunteers (15.8% vs. 0.6%; χ² = 71.902, P < 0.01), and there was a significant difference in the seroprevalence of anti-T. gondii antibody among patients with hematological tumors (18.2%), patients with non-tumor hematological diseases (10.0%) and healthy volunteers (χ² = 78.327, P < 0.01). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological tumors and non-tumor hematological diseases than among healthy volunteers (both P values < 0.05), while no significant difference was seen in the seroprevalence of anti-T. gondii antibody between patients with hematological tumors and non-tumor hematological diseases (P > 0.05). In addition, the proportion of history of cat or dog contacts was significantly higher among patients with hematological diseases that were positive for serum anti-T. gondii anti-body than among those negative for serum anti-T. gondii antibody (21.1% vs. 5.4%; χ² = 8.653, P < 0.05). Conclusions There is a high seroprevalene rate of T. gondii infections among hematological diseases, which is significantly greater than that among healthy volunteers.

BACKGROUND:Studies have shown that there are significant differences in the geometric morphology of the distal femur of different races and genders,and there are more short female patients in southern China,so the phenomenon of overhanging or insufficient coverage of imported knee prostheses often occurs during surgery. OBJECTIVE:To investigate the characteristics of distal femur bones in southern Chinese women and compare them with imported joint prostheses by simulating the three-dimensional reconstruction of the distal femur bone and matching the femoral side after osteotomy with common imported joint prostheses. METHODS:From January to December 2021,120 female volunteers underwent a CT scan of knee joints.The images were imported into Mimics 20.0 software in Dicom format for three-dimensional reconstruction and then imported into Magic 22.0 software to simulate osteotomy by posterior cruciate ligament preserved total knee arthroplasty and to conduct a matching study with a normal imported joint prosthesis. RESULTS AND CONCLUSION:(1)The functional anteroposterior dimension(fAP)of the distal femur and Persona matched prosthesis had a total overhang rate of 25%(30/120).The fAP≤47 mm group had an overhang than the other groups(P<0.05).The poor coverage rate of Triathlon prosthesis was 12.5%(15/120),and poor coverage was more likely in fAP>53 mm group than in fAP≤53 mm group(P<0.05).(2)The total poor coverage rate of femoral intercondylar width matching with Triathlon prosthesis was 27.5%(33/120).Therefore,the poor coverage rate of bone surface in the central region of the distal femur was more likely in the fAP≤47 mm group than in other groups(P<0.05).The overhang rate of Journey II was 21.6%(26/120),and the overhang rate was higher in the fAP>53 mm group than in the fAP≤53 mm group(P<0.05).(3)Journey II CR prosthesis had the largest difference with the length of the anterior mediolateral diameter of the femur,which was easy to hang out on the anterolateral side of the femoral prosthesis.The Persona CR prosthesis has the largest difference with the length of the posterior mediolateral diameter of the femur,which is easy to be poorly covered in the posterior medial part of the prosthesis.It is recommended to increase the femoral prosthesis with reduced mediolateral diameter in the fAP≤47 mm group and add wider and narrower sizes than the conventional size of intercondylar width,and optimize the anterolateral angular arc design of the femoral prosthesis to improve the matching of posterior cruciate ligament reserved knee prosthesis.

BACKGROUND:Prosthesis restricted selection,soft tissue release,patellar trajectory recovery,and bone defect reconstruction were need to be optimized in total knee arthroplasty for moderate and severe valgus knee.The medial parapatellar approach has disadvantages in the treatment of valgus knee,such as aggravating the medial soft tissue relaxation.In recent years,it has been found that the lateral parapatellar approach has advantages in the treatment of valgus knee,such as exposure and release. OBJECTIVE:To observe the efficacy of the lateral and medial parapatellar approach in total knee arthroplasty for moderate and severe valgus knee,and to explore a more suitable surgical approach for moderate and severe valgus knee. METHODS:Totally 56 patients with moderate and severe valgus knee underwent total knee arthroplasty and would take turns performing surgery through the medial and lateral parapatellar approach according to the order of admission.The lateral group(n=28)underwent total knee arthroplasty through lateral parapatellar approach,and the medial group(n=28)through medial parapatellar approach.Posterior stablized knee prosthesis was used in all patients.The restricted types of prosthesis,thickness of polyethylene,operation time,amount of blood loss,femoro-tibia angle,patellar tilt angle,range of motion,Hospital for Special Surgery score,Western Ontario and McMaster Universities Arthritis Index(WOMAC)score,and complications were collected as observation indexes for statistical analysis. RESULTS AND CONCLUSION:(1)The utilization rate of condyle-restricted prosthesis in the lateral group was significantly lower than that in the medial group.The average thickness of polyethylene liner was lower,and the operation time was shorter in the lateral group compared with the medial group.There were significant differences between the two groups(P<0.05),and there was no significant difference in the amount of surgical bleeding.(2)56 patients were followed up for an average of 2-5 years.There were no signs of prosthesis loosening or bone resorption in all patients.The average patellar tilt angle and femoral tibial angle of the lateral group were lower than those of the medial group,and the average Hospital for Special Surgery score and WOMAC score of the lateral group were higher than those of the medial group,with significant differences(P<0.05).There was no significant difference in the range of motion of the knees between the two groups.(3)Incision fat liquefaction and calf intermuscular venous thrombosis occurred in one case in each group.No infection,poor incision healing,incisional hematoma,prosthesis dislocation,iatrogenic nerve injury,ectopic ossification,or periprosthesis fracture occurred during follow-up.(4)In conclusion,the treatment of moderate and severe valgus knee by lateral parapatellar approach can better protect the tension of the medial soft tissue of the knee,use less condylar restrictive prostheses,and have a more friendly patellar trajectory and higher postoperative function score.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Humans ; Cohort Studies ; Body Mass Index ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Inflammation ; Treatment Outcome ; Risk Factors

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Objective:To investigate the effect of autophagy inhibitor 3-methyladenine (3-MA) on uric acid (UA)-induced apoptosis of renal tubular epithelial cells.Methods:(1) Totally 24 SD rats were randomly divided into 4 groups: control group, treatment with 3-MA group, hyperuricemic nephropathy (HN) group, and HN+3-MA group, with 6 rats in each group. According to the body weight of the rats, adenine (100 mg/kg) and potassium oxonate (1 500 mg/kg) were mixed with distilled water to make a suspension, and the rats were given intragastrically once daily for consecutive 21 days to establish HN rat model. The control group and the 3-MA treatment group were fed an equivalent amount of distilled water. At the same time, the 3-MA treatment group and the HN+3-MA group were intraperitoneally injected with 3-MA (15 mg/kg), and the control group and HN group were intraperitoneally injected with an equal volume of saline once daily for 21 consecutive days. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to observe renal cell apoptosis. Western blotting was used to detect the expression levels of cleaved caspase-3 and Bax, and immunofluorescence staining was used to detect the expression and localization of cleaved caspase-3 in renal tissue. (2) Human renal tubular epithelial cells (HK-2) were stimulated with UA (800 μmol/L), and cells were administrated with different concentrations of 3-MA or Beclin-1 small interfering RNA (siRNA). The apoptosis of renal tubular epithelial cells was detected by Western blotting and immunofluorescence staining.Results:Compared with the normal rats, the apoptosis of renal tubular epithelial cells in the HN group was significantly increased ( P<0.01), and the expression levels of cleaved caspase-3 and Bax were significantly up-regulated (both P<0.05). Compared with the HN group, the apoptosis of renal tubular epithelial cells in the HN+3-MA group was significantly decreased ( P<0.01). In addition, high level of uric acid could significantly increase the levels of apoptosis associated proteins in HK-2 cells (all P<0.05), and using different concentrations of 3-MA or transfecting with Beclin-1 siRNA could significantly reduce the expression of cleaved caspase-3 and Bax (all P<0.05). Conclusion:Autophagy plays an important role in uric acid-induced apoptosis of renal tubular epithelial cells. Inhibiting the excessive activation of autophagy may be a new strategy to prevent the progression of HN.