Objective: To analyze the hepatitis B virus serological markers (HBVM) and abnormal rates of liver function indexes among primary liver cancer (PLC) patients with different HBVM profiles, so as to provide a reference for risk stratification and optimization of diagnosis and treatment strategies for PLC patients. Methods: Patients diagnosed with PLC at Qidong People's Hospital between January 2017 and June 2024 were selected for this study. Basic information such as gender and age was collected through the hospital information management system. Venous blood samples were drawn to test for HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc, as well as ten liver function indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), cholinesterase (CHE), and adenosine deaminase (ADA). Compare the abnormal rates of liver function indexes among the six HBVM profiles: "big three yang" (HBsAg+, HBeAg+, anti-HBc+), "small three yang" (HBsAg+, anti-HBe+, anti-HBc+), triple antibody positive (anti-HBs+, anti-HBe+, anti-HBc+), s/c antibody positive (anti-HBs+, anti-HBc+), e/c antibody positive (anti-HBe+, anti-HBc+), and all negative. Results: A total of 1 434 patients with PLC were enrolled in this study. Among them, 1 043 (72.73%) were males and 391 (27.27%) were females. The median age was 64.00 (interquartile range, 16.00) years. The positive rates for HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc were 51.95%, 29.43%, 10.81%, 60.32%, and 88.42%, respectively. The "big three yang", "small three yang", triple-antibody positive, s/c antibody positive, e/c antibody positive, and all-negative profiles accounted for 85 (5.93%), 491 (34.24%), 170 (11.85%), 148 (10.32%), 100 (6.97%), and 121 (8.44%) cases, respectively. The abnormal rates of ALT among PLC patients with six HBVM profiles were 26.19%, 28.33%, 13.94%, 22.60%, 20.41%, and 14.91%, respectively. The abnormal rates of AST were 33.33%, 36.17%, 23.03%, 24.66%, 22.45%, and 18.42%, respectively. The abnormal rates of LDH were 62.16%, 68.22%, 53.73%, 61.19%, 60.00%, and 68.42%, respectively. The abnormal rates of CHE were 0%, 1.81%, 0%, 2.11%, 2.22%, and 3.88%, respectively. The abnormal rates of ADA were 59.09%, 57.27%, 24.27%, 33.33%, 45.00%, and 37.04%, respectively. These differences were statistically significant (all P<0.05). Conclusions In this study, the HBVM profiles were mainly characterized by "small triple positive" among PLC patients. The significant differences in liver function indexes abnormal rates among PLC patients with six HBVM profiles could reflect the liver injury status.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

OBJECTIVES: To analyze MYO1B expression in gastric cancer, its association with long-term prognosis and its role in regulating biological behaviors of gastric cancer cells. METHODS: We analyzed MYO1B expression in gastric cancer and its correlation with tumor grade, tumor stage, and patient survival using the Cancer Public Database. We also examined MYO1B expression with immunohistochemistry in gastric cancer and paired adjacent tissues from 105 patients receiving radical surgery and analyzed its correlation with cancer progression and postoperative 5-year survival of the patients. GO and KEGG enrichment analyses were used to explore the biological functions of MYO1B and the key pathways. In cultured gastric cancer cells, we examined the changes in cell proliferation, migration and invasion following MYO1B overexpression and knockdown. RESULTS: Data from the Cancer Public Database showed that MYO1B expression was significantly higher in gastric cancer tissues than in normal tissues with strong correlations with tumor grade, stage and patient prognosis (P<0.05). In the clinical tissue samples, MYO1B was significantly overexpressed in gastric cancer tissues in positive correlation with Ki67 expression (r=0.689, P<0.05) and the parameters indicative of gastric cancer progression (CEA ≥5 μg/L, CA19-9 ≥37 kU/L, G3-4, T3-4, and N2-3) (P<0.05). Kaplan-Meier analysis and multivariate Cox regression analysis suggested that high MYO1B expression was associated with decreased postoperative 5-year survival and was an independent risk factor (HR: 3.522, 95%CI: 1.783-6.985, P<0.05). MYO1B expression level was a strong predictor of postoperative survival (cut-off value: 3.11, AUC: 0.753, P<0.05). GO and KEGG analyses suggested that MYO1B may regulate cell migration and the mTOR signaling pathway. In cultured gastric cancer cells, MYO1B overexpression significantly enhanced cell proliferation, migration, and invasion and promoted the phosphorylation of Akt and mTOR. CONCLUSIONS High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is correlated with poor patient prognosis.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Movement ; Myosin Type I/genetics* ; Neoplasm Invasiveness ; Cell Line, Tumor ; Female ; Male

OBJECTIVES: To investigate the effect of monotropein on motor function recovery of mice with spinal cord injury (SCI) and explore the underlying mechanism. METHODS: Forty-five adult female C57BL/6 mice were randomized equally into sham operation group, SCI group, and SCI group with daily intraperitoneal monotropein injection. The mice in the former two groups received daily saline injections. Motor function of the mice was evaluated using BMS scores, slant plate test, and footprint analyses. Pathological changes and neuronal counts in the spinal cord were observed using HE, LFB, and Nissl staining. The biological functions of monotropein were explored using GO and KEGG enrichment analyses. NeuN/cleaved caspase-3 immunofluorescence assay and Western blotting were used to detect neuronal apoptosis in the spinal cord of the mice. In cultured HT22 cells, the effect of monotropein on TNF-α-induced cell apoptosis was evaluated using TUNEL staining and Western blotting. In monotropein-treated HT22 cells and SCI mice, the changes in the PI3K/AKT pathway were examined, and the effect of a PI3K/AKT pathway activator (IGF-1) on HT22 cell apoptosis and motor function recovery of SCI mice were observed. RESULTS: SCI mice with monotropein treatment showed significantly improved motor functions with reduced SCI areas and increased myelin retention and neuron counts in the spinal cord. Bioinformatics analysis suggested a role of PI3K/AKT signaling pathway in mediating the anti-apoptotic effects of monotropein. In SCI mice, monotropein obviously reduced apoptotic neurons, decreased expressions of cleaved caspase-3 and Bax and increased Bcl-2 expression in the spinal cord. In HT22 cells, monotropein significantly inhibited TNF-α-induced apoptosis and PI3K/AKT pathway activation. Treatment with IGF-1 obviously increased apoptosis of HT22 cells and exacerbated locomotor dysfunction in SCI mice. CONCLUSIONS Monotropein promotes motor function recovery in SCI mice by reducing neuronal apoptosis possibly by inhibiting the PI3K/AKT signaling pathway.
Animals ; Spinal Cord Injuries/metabolism* ; Apoptosis/drug effects* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Female ; Phosphatidylinositol 3-Kinases/metabolism* ; Neurons/pathology* ; Recovery of Function

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

OBJECTIVES: To investigate the therapeutic effect of the natural compound niranthin on Crohn's disease-like colitis in mice and explore the underlying molecular mechanisms. METHODS: In a mouse model of colitis induced by 2,4,6-trinitro-benzenesulfonic acid (TNBS), the therapeutic effect of niranthin was evaluated by observing the changes in body weight, disease activity index (DAI), and colon length of the mice. The levels of inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17A and IL-10) in the intestinal mucosal tissue were detected using ELISA and quantitative real-time PCR (qRT-PCR). TUNEL staining and Western blotting were used to assess intestinal epithelial cell apoptosis and the expressions of Bcl-2 and Bax. The expression levels of tight junction proteins (ZO-1 and claudin-1) and the activation of the p38/JNK signaling pathway were investigated using Western blotting, and diprovocim intervention experiments were conducted to explore the molecular regulatory mechanism of niranthin. RESULTS: Niranthin treatment significantly increased body weight of TNBS-treated mice, lowered the DAI and histological inflammation scores, and increased colon length of the mice. The niranthin-treated mouse models showed obviously reduced protein and mRNA levels of IL-6, IL-1β, IL-17A, and TNF-α and upregulated expression of IL-10 in the colon tissue. TUNEL staining and Western blotting demonstrated that niranthin significantly inhibited intestinal epithelial cell apoptosis and activated the anti-apoptotic pathway in the mouse models. Niranthin treatment obviously upregulated the expression levels of ZO-1 and claudin-1 and downregulated the phosphorylation levels of p38 and JNK in the colon tissues of the mice. Diprovocim intervention obviously attenuated the inactivation of the p38/JNK signaling pathway induced by niranthin in the mouse models. CONCLUSIONS Niranthin ameliorates TNBS-induced Crohn's disease-like colitis in mice by inhibiting intestinal epithelial cell apoptosis and protecting the integrity of the intestinal barrier via regulating the activation of the p38/JNK signaling pathway.
Animals ; Apoptosis/drug effects* ; Mice ; Intestinal Mucosa/drug effects* ; Crohn Disease/drug therapy* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Disease Models, Animal ; Signal Transduction/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Male

Objective:To investigate the influencing factors of enlarged perivascular space (PVS) in relapsing-remitting multiple sclerosis (RRMS) patients and their relationship with cognitive function.Methods:Twenty-seven individuals with RRMS (RRMS group) and 27 healthy controls (healthy control group) who presented to the Department of Neurology, the Sixth Medical Center of People′s Liberation Army General Hospital from July 2022 to November 2024 underwent cognitive function assessments. PVS volume fractions, lesion volumes, and brain volumes were calculated using FreeSurfer, FSL, and other relevant softwares. Group differences in PVS volume fractions, lesion volumes, brain volumes, and cognitive function assessments were compared. Furthermore, correlations between PVS volume fractions and lesion volumes, brain volumes, and cognitive function assessments were analyzed within the RRMS group.Results:Compared with the healthy control group, the RRMS group exhibited significantly higher PVS volume fractions in white matter (PVS_w) (3.14‰±0.29‰ vs 2.91‰±0.30‰, t=2.877, P=0.006) and PVS volume fractions in deep gray matter (PVS_d) (2.25‰±0.10‰ vs 2.17‰±0.09‰, t=2.681, P=0.010), indicating an enlargement of the PVS. Compared with the healthy control group, the RRMS group showed a significant decrease in both white matter volumes [297.3 (274.3, 340.2) ml vs (324.2 (311.0, 350.0) ml, U=-2.085, P=0.037] and deep grey matter volumes [40.2 (34.9, 43.6) ml vs 42.7 (40.2, 44.8) ml, U=-2.292, P=0.022]. Compared with the healthy control group, the RRMS group showed significantly lower scores in cognitive function assessments ( P<0.05). Univariate analysis showed that PVS_w in the RRMS group was significantly positively correlated with age ( r=0.486), white matter lesion volumes ( r=0.437) and deep gray matter lesion volumes ( r=0.394;all P<0.05); PVS_d was also significantly positively correlated with white matter lesion volumes ( r=0.418) and deep gray matter lesion volumes ( r=0.480; both P<0.05). Multiple linear regression analysis showed that age ( B=0.011,95% CI 0.004-0.017), white matter lesion volumes ( B=0.026,95% CI 0.011-0.040) and deep gray matter lesion volumes ( B=0.401,95% CI 0.032-0.771) in the RRMS group were significantly positively correlated with PVS_w, while white matter lesion volumes ( B=0.007,95% CI 0.001-0.014) and deep gray matter lesion volumes ( B=0.204,95% CI 0.029-0.380) were significantly positively correlated with PVS_d (both P<0.05). Univariate analysis showed that immediate memory score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.428), and was significantly positively correlated with education level ( r=0.471), deep gray matter volumes ( r=0.530) and total brain volumes ( r=0.389; all P<0.05); short-term delayed memory score in the RRMS group was significantly negatively correlated with age ( r=-0.390), PVS_w ( r=-0.417) and white matter lesion volumes ( r=-0.438), and was significantly positively correlated with gender ( r=0.393), white matter volumes ( r=0.478), deep gray matter volumes ( r=0.579) and total brain volumes ( r=0.602;all P<0.05); verbal fluency test score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.409) and was significantly positively correlated with education level ( r=0.419) and total brain volumes ( r=0.400;all P<0.05). Multiple linear regression analysis revealed that PVS_d ( B=-5.572, 95% CI -11.513--0.368) and brain volumes ( B=0.012, 95% CI 0.001-0.023) in the RRMS group were both significant predictors of immediate recall score, while PVS_d ( B=-14.203,95% CI -27.514--0.891) was an independent predictor of verbal fluency test score (all P<0.05). Conclusions:The PVS is enlarged in individuals with RRMS compared with the healthy controls, and increased lesion volumes may be a significant predictor. Furthermore, enlarged PVS in the deep gray matter may be a significant predictor of impairment of verbal memory and verbal function in individuals with RRMS.

Objective:To investigate the influencing factors of enlarged perivascular space (PVS) in relapsing-remitting multiple sclerosis (RRMS) patients and their relationship with cognitive function.Methods:Twenty-seven individuals with RRMS (RRMS group) and 27 healthy controls (healthy control group) who presented to the Department of Neurology, the Sixth Medical Center of People′s Liberation Army General Hospital from July 2022 to November 2024 underwent cognitive function assessments. PVS volume fractions, lesion volumes, and brain volumes were calculated using FreeSurfer, FSL, and other relevant softwares. Group differences in PVS volume fractions, lesion volumes, brain volumes, and cognitive function assessments were compared. Furthermore, correlations between PVS volume fractions and lesion volumes, brain volumes, and cognitive function assessments were analyzed within the RRMS group.Results:Compared with the healthy control group, the RRMS group exhibited significantly higher PVS volume fractions in white matter (PVS_w) (3.14‰±0.29‰ vs 2.91‰±0.30‰, t=2.877, P=0.006) and PVS volume fractions in deep gray matter (PVS_d) (2.25‰±0.10‰ vs 2.17‰±0.09‰, t=2.681, P=0.010), indicating an enlargement of the PVS. Compared with the healthy control group, the RRMS group showed a significant decrease in both white matter volumes [297.3 (274.3, 340.2) ml vs (324.2 (311.0, 350.0) ml, U=-2.085, P=0.037] and deep grey matter volumes [40.2 (34.9, 43.6) ml vs 42.7 (40.2, 44.8) ml, U=-2.292, P=0.022]. Compared with the healthy control group, the RRMS group showed significantly lower scores in cognitive function assessments ( P<0.05). Univariate analysis showed that PVS_w in the RRMS group was significantly positively correlated with age ( r=0.486), white matter lesion volumes ( r=0.437) and deep gray matter lesion volumes ( r=0.394;all P<0.05); PVS_d was also significantly positively correlated with white matter lesion volumes ( r=0.418) and deep gray matter lesion volumes ( r=0.480; both P<0.05). Multiple linear regression analysis showed that age ( B=0.011,95% CI 0.004-0.017), white matter lesion volumes ( B=0.026,95% CI 0.011-0.040) and deep gray matter lesion volumes ( B=0.401,95% CI 0.032-0.771) in the RRMS group were significantly positively correlated with PVS_w, while white matter lesion volumes ( B=0.007,95% CI 0.001-0.014) and deep gray matter lesion volumes ( B=0.204,95% CI 0.029-0.380) were significantly positively correlated with PVS_d (both P<0.05). Univariate analysis showed that immediate memory score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.428), and was significantly positively correlated with education level ( r=0.471), deep gray matter volumes ( r=0.530) and total brain volumes ( r=0.389; all P<0.05); short-term delayed memory score in the RRMS group was significantly negatively correlated with age ( r=-0.390), PVS_w ( r=-0.417) and white matter lesion volumes ( r=-0.438), and was significantly positively correlated with gender ( r=0.393), white matter volumes ( r=0.478), deep gray matter volumes ( r=0.579) and total brain volumes ( r=0.602;all P<0.05); verbal fluency test score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.409) and was significantly positively correlated with education level ( r=0.419) and total brain volumes ( r=0.400;all P<0.05). Multiple linear regression analysis revealed that PVS_d ( B=-5.572, 95% CI -11.513--0.368) and brain volumes ( B=0.012, 95% CI 0.001-0.023) in the RRMS group were both significant predictors of immediate recall score, while PVS_d ( B=-14.203,95% CI -27.514--0.891) was an independent predictor of verbal fluency test score (all P<0.05). Conclusions:The PVS is enlarged in individuals with RRMS compared with the healthy controls, and increased lesion volumes may be a significant predictor. Furthermore, enlarged PVS in the deep gray matter may be a significant predictor of impairment of verbal memory and verbal function in individuals with RRMS.

Objective:To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function.Methods:Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains.Results:Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens ( P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment ( r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory ( r=0.45, P=0.047) and information processing speed impairment ( r=0.50, P=0.026). Conclusions:Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

A 1-year and 9-month-old male proband presented with clustered rice grain-sized flat smooth red papules on the face, trunk and limbs for 1.5 years, without fever, joint swelling, or pain. The proband′s sister aged 7 years ever experienced swelling and pain in the finger joints of both hands at the age of 2 years, and had intermittent fever and papules all over the body at the same time, and the papules gradually regressed with the subsidence of fever. The proband′s mother aged 27 years suffered from swelling and pain in the finger joints of both hands when she was young, gradually leading to finger deformities, and experienced intermittent knee swelling and pain at the age of 12 years without obvious skin lesions on the body. No abnormality was found in ophthalmological and systemic physical examinations of the 3 patients. Whole-exome sequencing showed that the proband, his sister and mother all had a heterozygous missense mutation c.1001G>A (p.R334Q) in exon 4 of the NOD2 gene. A diagnosis of Blau syndrome was made. The proband was treated with topical moisturizing cream all over the body; during the 52-week follow-up, no joint swelling and pain or eye symptoms were found in the proband, while erythema and depressed scars were observed on the face, trunk and limbs. The proband′s sister and mother were treated with subcutaneous injections of adalimumab at initial doses of 40 mg and 80 mg respectively, followed 1 week later by injections at 20 mg and 40 mg respectively, and then treated with injections at 20 mg and 40 mg respectively every 2 weeks; after 12-week treatment, the joint swelling and pain were markedly relieved in the proband′s sister and mother, and most skin lesions subsided in the proband′s sister; at week 52 during the follow-up, there was no joint swelling, pain or skin lesions in the proband′s sister, and there was no swelling or pain in the knee joints of the proband′s mother, while no improvement was observed in her finger deformities. During the treatment, no eye symptoms or adverse reactions were observed neither in the proband′s sister nor in his mother.