BACKGROUND:Developed by the esteemed Chinese medicine master Wei Guikang,Tongan Decoction has proven highly effective in treating knee osteoarthritis.However,the mechanism of action is yet unclear.OBJECTIVE:To elucidate how Tongan Decoction modulates synovial macrophage polarization as a therapeutic strategy for knee osteoarthritis in a rat model.METHODS:(1)We employed high-throughput microRNA sequencing and polymerase chain reaction to analyze the differentially expressed miRNA in synovial macrophages of normal and knee osteoarthritis rats.Predicted target genes of miR-27a were identified using bioinformatics databases,with subsequent validation through luciferase assays.A total of 68 Sprague-Dawley rats were randomly divided into normal control group(n=16),model group(n=16),miR-27a overexpression group(n=12),Tongan Decoction group(n=12),and Tongan Decoction+miR-27a inhibition group(n=12).The miR-27a overexpression group and the Tongan Decoction+miR-27a inhibition group were injected with miR-27a mimic and miR-27a inhibitor in the right knee joint cavity,respectively,once daily for 5 continuous days.On the 15th day after modeling,the Tongan Decoction group and the Tongan Decoction+miR-27a inhibition group were given Tongan Decoction by gastric lavage,and the other three groups were given saline by gastric lavage,once daily for 14 continuous days.After administration,behavioral tests,X-rays,hematoxylin-eosin staining of synovial and cartilage tissues of the knee joint and immunofluorescence staining of synovial tissues of the knee joint,RT-PCR,and Western blot were performed.RESULTS AND CONCLUSION:High-throughput sequencing of miRNA showed low expression of miR-27a in synovial tissues of rats with knee osteoarthritis.The target gene of miR-27a was nuclear factor κB,and luciferase assay showed that the two could bind to each other.Behavioral assays showed that miR-27a overexpression or Tongan Decoction alleviated joint dysfunction in rats with knee osteoarthritis,and miR-27a inhibition antagonized the effect of Tongan Decoction.X-ray films and hematoxylin-eosin staining showed that miR-27a overexpression or Tongan Decoction reduced the degree of knee osteoarthritis and miR-27a inhibition weakened the therapeutic effect of Tongan Decoction.The results of RT-PCR and western blot assay showed that compared with the normal control group,the expression of interleukin 10 was reduced in the model group(P＜0.05),and the expression of matrix metalloproteinase 13,interleukin 1β,and nuclear factor κB was elevated in the model group(P＜0.05).miR-27a overexpression or Tongan Decoction could differently reverse the changes in the above-mentioned indexes,while miR-27a inhibition weakened the effect of Tongan Decoction.Immunofluorescence staining results showed that CD86 protein expression in the model group was higher than that in the normal control group(P＜0.05),and CD206 protein expression was lower than that in the normal control group(P＜0.05);miR-27a overexpression group and Tongan Decoction had lower CD86 protein expression than that in the model group(P＜0.05),and higher CD206 protein expression than that in the model group(P＜0.05);in the Tongan Decoction+miR-27a inhibition group,CD86 protein expression was higher(P＜0.05)and CD206 protein expression was lower than that in the Tongan Decoction group(P＜0.05).Tongan Decoction mitigates knee osteoarthritis by upregulating miR-27a expression and suppressing nuclear factor κB activity,which improves knee joint function and further treats knee osteoarthritis.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To investigate the electrophysiological characteristics of medium spiny neurons(MSNs)expressing D1 or D2 dopamine receptors in the striatum of mice,providing a theoretical basis for exploring their roles in motor disorders,reward,and anxiety-depression.Methods:Six male adult D1-tdTomato and D2-tdTomato mice were used.After anesthesia and decapitation,the brains were quickly removed,and coronal slices were prepared.Whole-cell patch recording were employed to record spontaneous firing,resting membrane potential,and action potential parameters of D1 and D2 MSNs in the striatum.Comparative analyses were conducted to identify differences between the two types of neurons.Results:The frequency of spontaneous excitatory postsynaptic currents(sEPSCs)in D1-MSNs was signifi-cantly lower than that in D2-MSNs(P＜0.001),but there was no difference in amplitude;whereas no significant differences were observed in the frequency or amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs)between D1-MSNs and D2-MSNs.Compared with D1-MSNs,D2-MSNs had a lower resting membrane potential(P＜0.01),a significantly lower rheobase for action potential generation(P＜0.01),and the frequency of action potentials induced by depolarizing current injection was significantly higher in D2-MSNs(P＜0.001).Following perfusion with dopamine(60 μmol/L),the frequency of action potentials in D1-MSNs significantly increased(P＜0.001),while the frequency of action potentials in D2-MSNs significantly decreased(P＜0.001).Conclusion:There are significant differences in the electrophysiological properties between D1-MSNs and D2-MSNs in the striatum of mice.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of genital herpes in China from 2010 to 2023 and provide evidence for the prevention and control of genital herpes.Methods:The reported data of genital herpes cases in 31 provinces (autonomous regions and municipalities) in China from 2010 to 2023 were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Software Joinpoint 5.2.0 was used to analyze the epidemiological characteristics of genital herpes, software ArcGIS 10.5 was used for spatial autocorrelation analysis, and software SaTScan 10.2.3 was used for spatiotemporal scanning analysis.Results:The reported incidence rate of genital herpes increased from 1.58/100 000 to 2.00/100 000 in China from 2010 to 2023, with an average annual percentage change of 0.90%. The upward trend of reported incidence rate was significant ( t=2.35, P=0.037). There was a positive spatial autocorrelation in the reported incidence of genital herpes with the global Moran's I ranging from 0.36 to 0.51 (all P<0.001). Local spatial autocorrelation analysis showed that the number of hotspots increased from 144 in 2010 to 232 in 2023, mainly distributed in provinces Zhejiang, Guangdong, Guangxi, Chongqing and Hunan. The number of hotspots in of Chongqing, Sichuan, Yunnan and Guizhou increased significantly from 7 to 57. A total of 67 spatiotemporal clusters were detected by spatiotemporal scanning analysis, mainly distributed in Guangdong from 2011 to 2015, in Zhejiang and Fujian from 2015 to 2019, and in Chongqing and Guizhou from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence of genital herpes in China showed an upward trend, and there was an obvious spatiotemporal clustering of genital herpes. The distribution of hotspots was basically consistent with the distribution of spatiotemporal clustering areas, mainly distributed in the southeastern coastal area and southwestern region, and the spatiotemporal clustering areas gradually changed from the southeast coastal area to the southwest region.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of genital herpes in China from 2010 to 2023 and provide evidence for the prevention and control of genital herpes.Methods:The reported data of genital herpes cases in 31 provinces (autonomous regions and municipalities) in China from 2010 to 2023 were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. Software Joinpoint 5.2.0 was used to analyze the epidemiological characteristics of genital herpes, software ArcGIS 10.5 was used for spatial autocorrelation analysis, and software SaTScan 10.2.3 was used for spatiotemporal scanning analysis.Results:The reported incidence rate of genital herpes increased from 1.58/100 000 to 2.00/100 000 in China from 2010 to 2023, with an average annual percentage change of 0.90%. The upward trend of reported incidence rate was significant ( t=2.35, P=0.037). There was a positive spatial autocorrelation in the reported incidence of genital herpes with the global Moran's I ranging from 0.36 to 0.51 (all P<0.001). Local spatial autocorrelation analysis showed that the number of hotspots increased from 144 in 2010 to 232 in 2023, mainly distributed in provinces Zhejiang, Guangdong, Guangxi, Chongqing and Hunan. The number of hotspots in of Chongqing, Sichuan, Yunnan and Guizhou increased significantly from 7 to 57. A total of 67 spatiotemporal clusters were detected by spatiotemporal scanning analysis, mainly distributed in Guangdong from 2011 to 2015, in Zhejiang and Fujian from 2015 to 2019, and in Chongqing and Guizhou from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence of genital herpes in China showed an upward trend, and there was an obvious spatiotemporal clustering of genital herpes. The distribution of hotspots was basically consistent with the distribution of spatiotemporal clustering areas, mainly distributed in the southeastern coastal area and southwestern region, and the spatiotemporal clustering areas gradually changed from the southeast coastal area to the southwest region.

Objective:To investigate and evaluate the correct cognition and influencing factors of mpox expertise among relevant Chinese clinicians and to provide a reference for prevention and control.Methods:A cross-sectional survey was conducted among clinicians in relevant departments using a structured questionnaire compiled by ourselves through a non-random network recruitment method. The content includes demography, clinical specialties, and characteristics of medical institutions, and 37 questions to evaluate the professional cognition of mpox etiology, clinical characteristics, transmission, prevention, and control. Using the modified Bloom's cutoff point to determine the correct answer is greater than or equal to 26 entitled correct cognition. A logistic regression model was used to analyze the factors influencing the correct cognition rate.Results:A total of 4 332 clinicians in 23 provinces (autonomous regions, municipality) in China were investigated by online questionnaires and 4 276 effective questionnaires were collected, with an effective rate of 98.71%. The mean age of the respondents was (39.46±9.54) years old, 61.18% were female. The overall correct cognition rate of mpox expertise was 62.04% (95% CI: 60.59%-63.50%), the correct cognition rates of mpox etiology, clinical characteristics, transmission, prevention and control were 48.25% (95% CI: 46.68%-49.82%), 78.66% (95% CI: 77.38%-79.95%), 68.56% (95% CI: 67.10%-70.02%), respectively. Multivariate logistic regression analysis showed that the relevant factors affecting the overall correct cognition of mpox expertise among Chinese clinicians included gender (female: OR=1.54, 95% CI: 1.31-1.80), region (eastern region: OR=1.46, 95% CI: 1.18-1.79; midwestern region: OR=1.24, 95% CI: 1.04-1.49), professional title (deputy senior: OR=1.43, 95% CI:1.16-1.76; senior: OR=1.72, 95% CI:1.30-2.28), the clinical field (the clinical fields of dermatology and venereal diseases: OR=1.78, 95% CI: 1.42-2.23). Conclusions:The overall correct cognition rate of mpox expertise among relevant Chinese clinicians was low. It was essential to conduct mpox knowledge training for clinicians in males, northeast regions, junior professional title and the clinical fields other than dermatology and venereal diseases to improve their correct cognition rates and epidemic prevention and control ability.

The paper reports a 32-year-old female acute myeloid leukemia patient who developed graft-versus-host disease after paternal hematopoietic stem cell transplantation, which subsequently led to renal thrombotic microangiopathy. She subsequently required a kidney transplant from the same donor 5 years later due to renal failure. Considering that both the bone marrow and kidney were from the same donor and the recovery of renal function was favorable, immunosuppressive therapy was discontinued after a short course of anti-rejection treatment, with maintained stable kidney function. This case suggests that under the condition of high chimerism, allogeneic hematopoietic stem cell transplantation and kidney transplantation from the same donor can achieve immune tolerance, potentially improving solid organ transplantation success rate. The findings provide a novel therapeutic approach for solid organ transplantation following allogeneic hematopoietic stem cell transplantation.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.