Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Objective:To retrieve, evaluate and summarize relevant evidence on home-based exercise management in patients with mild to moderate Parkinson's disease, so as to provide reference and guidance for clinical healthcare professionals to construct and improve patient home-based exercise intervention plans.Methods:According to the top-down principle of the "6S" evidence model, UpToDate, BMJ, National Institute for Health and Clinical Excellence, Guidelines International Network, National Guideline Clearinghouse, Medlive, Clinical Guidelines Network, Joanna Briggs Institute, Cochrane Library, PubMed, CINAHL, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, VIP and China Biology Medicine Disc were systematically searched for relevant literature on home-based exercise management in patients with Parkinson's disease, including guidelines, expert consensuses, systematic reviews, evidence summaries, clinical decisions, recommended practices and best practices. The search period was from the establishment of the databases to October 31, 2022. Two researchers independently evaluated the quality of the literature and extracted and integrated evidence.Results:A total of 27 articles were included, including three guidelines, five expert opinions and consensuses, three clinical practice suggestions, 15 systematic evaluations and one clinical decision. A total of 45 pieces of evidence were summarized from six aspects, such as organizational management, health education, exercise evaluation, exercise prescription, family and social support and monitoring guidance.Conclusions:This study summarized the best evidence of home-based exercise management for patients with mild to moderate Parkinson's disease, which can provide evidence-based basis for clinical staff to formulate home-based exercise management programs and standardize practice standards.

Zi goose is a small local variety with high fecundity,good meat quality,roughage resist-ance,strong adaptability and excellent down quality.It is an excellent female parent for cross breeding among varieties.With the rapid development of goose industry,the variety of Zi goose has not been well protected,the variety is hybrid and degraded seriously,and the number of pure Zi goose is decreasing day by day.This paper reviewed the research progress on the breeding distribu-tion and preservation status of Zi goose and the variety characteristics of Zi goose,in order to pro-vide reference for the research,protection and utilization of germplasm resources of Zi goose and the stable development of goose industry.

The chemical constituents of solid rice culture of the endophytic fungus Aspergillus sp.Dq-25 from barnacle were isolated and purified by silica gel, Sephadex LH-20, C18 reversed silica gel column chromatography and recrystallization.Their structures were identified by the physical and chemical properties, and by various spectroscopic methods.Six compounds were isolated and identified as: demethyldihydropenicillic acid (1), dihydropenicillic acid (2), penicillic acid (3), fortisterol (4), 22E, 24R-3P, 5a-dihydroxyerogosta-7, 22-diene-6-one (5), and (22E, 24R)-ergosterol-7, 22-diene-3β, 5α, 9α-triol-6-one (6).Compound 1 was a new butyrolactone.MTT method was used to analyze cytotoxicity, and the result showed that compound 3 exhibited inhibitory activity on five cell lines, including K562, HeLa, SGC-7901, A542 and BEL-7402, with IC50 values of 38.0 ~ 105.0 μmol/L.

Objective To explore the effect of topical application of Fushan rheumatism external prescription on inflammatory cytokines and notch2 pathway in rats with collagen-induced arthritis(CIA).Methods 36 female Wistar rats were randomly divided into normal group(n=10)and model group(n=26).CIA model was successfully established in 20 rats,which were randomly divided into model group(n=10)and Fushan rheumatism external prescription group(n= 10).Treatment was initiated on day 14,and 0.4 mL ointment was evenly applied to the ankle joints of rats in Fushan rheumatism external prescription group.Normal group and model group were topical smeared with the same volume of normal saline.Activity was taken twice a day for 42 days.The joint swelling of rats was observed every week and the arthritis index was scored.Thereafter blood was collected from abdominal aorta,and then ankle joint,spleen,liver,and kidney of rats were taken out after the end of the interventions.The severity of arthritis and the pathological changes of ankle joint,liver and kidney were evaluated by HE staining;Inflammatory cytokines expression in serum were detected by ELISA;The expression of Notch2,Delta-like ligand protein 1(delta-like ligand protein-1,DLL1)and nuclear factor-κ Bp65(nuclear factor-κ Bp65,NF-κ Bp65)mRNA and protein in synovium of ankle joints and spleen were detected by qRT-PCR and Western blot,and its positive expression in ankle joints were detected by immunohistochemical method;The changes of liver and kidney function of rats in each group were detected in serum.Results Compared with normal group,the arthritis index score in model group were increased(P<0.01),joint injury and pathological score were increased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were increased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were increased(P<0.01),and the positive expression in joints were also increased(P<0.01);Compared with model group,the arthritis index score in Fushan rheumatism external prescription group were decreased(P<0.05,P<0.01),joint injury and pathological score were decreased(P<0.01),the levels of inflammatory cytokines TNF-α,IL-6,IL-17 and IFN-γ in serum were decreased(P<0.01),the expression of Notch2,DLL1 and NF-κBp65 mRNA and protein in joints and spleen were decreased(P<0.01),and the positive expression in joints were also decreased(P<0.01).In addition,no noticeable tissue damages were observed in liver and kidney in Fushan rheumatism external prescription group,and the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN)and creatinine(Cr)in serum were no changes(P>0.05).Conclusion Fushan rheumatism external prescription relieves arthritis symptoms and joint injury in CIA rats,and has no toxic and side effects on liver and kidney.Its mechanism may be related to the reduction of inflammatory cytokines and down-regulation of Nocth2 pathway.

Objective:To investigate the level and clinical significance of peripheral blood CD4 +T cell subpopulations in late-onset systemic lupus erythematosus (SLE) patients. Methods:This study included 260 SLE patients hospitalized in the Rheumatology and Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to December 2021: of whom 58 and 202 were late- (≥50 years) and adult-(18~49 years) onset patients. This study also included 160 subjeces as healthy controls(HCs), of whom 35 and 125 were Control Group 1 (≥50 years) and Control Group 2 (18~49 years). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. The clinical data of all patients and healthy controls (HCs)were recorded. The differences between the groups were analyzed by Mann-Whitney U test or χ2 test. Results:(1)The time of diagnosis of late-onset SLE was longer than that of adult-onset SLE [Median time: 5.0 (2.0, 24.0)months vs 3.0 (1.0, 7.3)months, Z=-3.13, P=0.002]. Compared with adult-onset SLE, the SLEDAI score of late-onset SLE was lower [12.0 (8.0, 15.2) vs 14.0 (10.0, 18.0), Z=-2.12, P=0.034]. Some manifestations occurred more frequently in late-onset SLE, such as weight loss, nausea, abdominal pain, cerebral infarction, interstitial pneumonitis, Sj?gren′s syndrome and infection. The manifestations of skin and mucos a occurred less frequently in late-onset SLE. (2)CD4 +T cell subpopulations: ①The absolute counts of Treg, Th17, Th1 and Th2 cells in the peripheral blood of patients with late-onset SLE were significantly lower than those of HCs [Treg: 10.94 (6.14, 19.23) vs 32.65 (28.07, 41.65), Z=-6.79, P<0.001; Th17: 3.43 (0.94, 5.64) vs 6.13 (3.77, 7.82), Z=-3.24, P=0.001; Th1: 36.02 (10.80, 76.38) vs 128.70(89.82, 159.89), Z=-5.29, P<0.001; Th2:3.56 (1.56, 6.06) vs 8.25 (4.69, 12.98), Z=-4.57, P<0.001]. The ratio of Th17/Treg cells was higher than that of HCs[0.28(0.13, 0.59) vs 0.17 (0.12, 0.28), Z=-2.38, P=0.017].②The absolute counts of Treg, Th17, Th1 and Th2 cells in peripheral blood of patients with adult-onset SLE were significantly lower than those of HCs [Treg: 10.28 (5.37, 17.04) vs.30.19 (21.20, 39.75), Z=-11.28, P<0.001; Th17: 3.44 (1.84, 6.14) vs 6.48 (4.23, 10.66), Z=-6.53, P<0.001; Th1: 29.59(15.14, 56.81) vs 90.75(42.67, 162.00), Z=-7.01, P<0.001; Th2: 2.74 (1.62, 4.77) vs 8.25 (4.75, 11.99), Z=-9.91, P<0.001]. The ratio of Th17/Treg was higher than that of HCs[0.35 (0.17, 0.65) vs 0.23(0.14, 0.37), Z=-3.89, P<0.001].③The ratios of Th17/Treg in patients with late-and adult-onset SLE were higher than those of HCs. The ratio of Th17/Treg was the highest in adult-onset SLE patients. Conclusion:Patients with late-onset SLE have reduced numbers of Treg cells and the immune imbalanced of Th17/Treg. However, the immune imbalance of Th17/Treg in late-onset SLE patients is milder than that in adult-onset SLE patients, which may be related to lower disease activity.

Objective:To investigate the level of peripheral blood regulatory T cells in rheumatoid arthritis (RA) patients with cardiovascular disease (CVD) and its clinical significance.Methods:A total of 191 patients with RA in the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Shanxi Medical University and 86 healthy controls (HCs) were enrolled from January 2019 to January 2021. All peripheral blood CD4 + T lymphocyte subsets of participants were assessed by flow cytometry. Patients were divided into RA-CVD group ( n=71) and RA only group ( n=120) and their clinical data were recorded. The differences between the groups were analyzed by Independent-Samples t test, Mann-Whitney U test or χ2 test, and risk factors that affected CVD were analyzed using Logistic regression. Results:① The age of patients and the proportion of male patients in the RA-CVD group were significantly higher than those in the RA only group [age: (64±10) years old vs (56±12) years old, t=-4.16, P<0.001; male patients: 35 cases vs 31 cases, χ2=10.86, P=0.001]. ② The level of Treg cells in the peripheral blood of patients with RA only and RA-CVD groups was significantly lower than that of HCs ( Z=-4.14, P<0.001; Z=-6.27, P<0.001), while the numbers of peripheral Th17 cells in the two groups of patients were not significantly different from those of HCs ( P>0.05). The ratios of Th17/Treg cells in the two group patients were higher than those of HCs, but only the difference between RA-CVD patients and HCs was significant ( Z=-5.49, P<0.001). ③ Compared with the RA only group, the absolute number of Treg cells in peripheral blood of RA-CVD group was significantly lower [19.00(13.62, 26.73) vs 24.94 (19.32, 34.12), Z=-3.19, P=0.001], the level of Th17 cells was significantly higher [absolute number: 7.77 (3.86, 13.64) cell/μl vs 5.59 (3.49, 8.91) cells/μl, Z=-2.14, P=0.033; percentage: 1.37%(0.78, 2.00)% vs 0.80%(0.56, 1.24)%, Z=-4.20, P<0.001], and the ratio of Th17/Treg cells was significantly higher [0.40(0.24, 0.62) vs 0.23(0.14, 0.35), Z=-4.46, P<0.001]. ④ Logistic regression analysis showed that Treg cell [ OR(95% CI)=0.934 (0.903, 0.967)] was a protective factor, while elder age [ OR(95% CI)=1.038(1.003, 1.074), male [ OR(95% CI)=2.450(1.005, 5.973)], hypertension [ OR(95% CI)=2.654 (1.219, 5.779)] and Th17 cell [ OR (95% CI)=1.066 (1.019, 1.116)] were risk factors of RA complicated with CVD. Conclusion:The level of Treg cells in peripheral blood of RA patients with CVD decreases significantly, and the immune imbalance of Th17/Treg is more singificant than that of RA patients without CVD. It is suggested that the immune imbalance and dysfunction caused by the number and/or functional deficiency of Treg cells may be involved in the occurrence and development of RA complicated with CVD.