Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To learn about the epidemiological and clinical characteristics of human brucellosis in Shaanxi Province, and to provide reference for brucellosis prevention and control.Methods:Through the China Disease Control and Prevention Information System and the Shaanxi Provincial Brucellosis Prevention and Control Work System, report data and case investigation data on human brucellosis cases in Shaanxi Province from 2020 to 2022 were collected, respectively, and the epidemiological characteristics, exposure history and clinical manifestations of the cases were analyzed descriptively.Results:A total of 4 240 human cases of brucellosis were reported in Shaanxi Province from 2020 to 2022, with no death. The average annual incidence was 3.60/100 000, with an average growth rate of 22.33%. Cases of brucellosis were reported from January to December throughout the year, mainly from April to August, accounting for 63.40% (2 688/4 240). Cases of brucellosis were reported in 12 prefectures (including Yangling District and prefecture-level administrative divisions directly administered by the province) and 90 counties (districts and cities), accounting for 79.65% (90/113) of the total number of counties (districts and cities). The male to female ratio of the cases was 2.92 ∶ 1.00 (3 159 ∶ 1 081). The onset age was mainly from 30 to 74 years old, accounting for 89.81% (3 808/4 240). Farmer was the main occupation, accounting for 87.12% (3 694/4 240). A total of 4 223 cases were investigated in Shaanxi Province from 2020 to 2022, with the acute phase being the main stage of disease progression, accounting for 94.67% (3 998/4 223); hospitalized cases accounted for 59.79% (2 525/4 223); the main risk occupations of brucellosis were rearing and grazing, accounting for 78.43% (3 312/4 223). The main exposure routes were direct contact through skin and mucous membranes and respiratory infection, accounting for 95.07% (4 015/4 223). There were 4 015 cases with a history of contact with livestock and their products, with sheep being the main type of contact (accounting for 96.91%, 3 891/4 015), and the possible infection sites were mainly at home (58.53%, 2 350/4 015). The main clinical symptoms were fever, muscle and joint pain, fatigue and excessive sweating, accounting for 75.49% (3 188/4 223), 58.23% (2 463/4 223), 68.17% (2 879/4 223) and 63.65% (2 688/4 223), respectively. A total of 139 Brucella strains were isolated and cultured, with sheep type 3 being the main bacterial type, accounting for 75.54% (105/139). Conclusions:The epidemic of brucellosis in Shaanxi Province is showing a clear upward trend, and the scope of the epidemic is becoming wider and wider. The incidence of brucellosis is mainly in free-range households, and the course of the disease is mostly in the acute phase. Brucellosis is mainly caused through direct contact with the skin and mucous membranes and respiratory infections. The clinical manifestations are diverse but non-specific. It is necessary to effectively improve the personal protection awareness and level of high-risk groups to reduce the occurrence of brucellosis.

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

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.

Objective:To investigate changes in disease status and their influencing factors in patients with moderate to severe plaque psoriasis treated with biologics during the coronavirus disease 2019 (COVID-19) pandemic.Methods:Through printed or electronic questionnaires during February 10 th - 20 th, 2023, data were collected from patients with moderate to severe plaque psoriasis treated with biologics in Henan Provincial People′s Hospital from June 2019 to January 2023, and changes in the disease condition during the COVID-19 pandemic were investigated. The t test or chi-square test was used for comparisons between groups, univariate analysis and multivariate logistic regression analysis were conducted to investigate the factors contributing to the exacerbation of psoriasis, and stratified analysis was employed to evaluate the disease progression among the patients receiving different biologic therapies following treatment delays. Results:A total of 177 patients with moderate to severe plaque psoriasis were collected, including 115 males and 62 females; they were aged 6 - 83 (38.69 ± 14.18) years, with disease duration of 1 - 50 (13.48 ± 9.70) years. Among the patients, 74 (41.81%) experienced psoriasis exacerbation, 154 (87.01%) developed COVID-19, and 90 (50.85%) experienced delays in psoriasis treatment due to the pandemic. The results of univariate analysis indicated significant associations of psoriasis exacerbation with treatment delays, irregular treatment before the pandemic, and incomplete clearance of skin lesions ( P < 0.001 or 0.05), while no correlations were observed between psoriasis exacerbation and COVID-19 or gender (both P > 0.05). Multivariate logistic regression analysis demonstrated that psoriasis exacerbation was associated with treatment delays due to COVID-19 ( OR = 3.34, 95% CI: 1.35 - 8.22, P = 0.009) and incomplete clearance of skin lesions ( OR = 3.10, 95% CI: 1.28 - 7.50, P = 0.012), but not associated with irregular treatment before the pandemic ( P = 0.130). Among the patients treated with adalimumab, secukinumab, ustekinumab, and ixekizumab, those experiencing treatment delays exhibited higher rates of psoriasis exacerbation than those without treatment delays (all P < 0.05) . Conclusion:Patients with moderate to severe plaque psoriasis undergoing biologic therapy are prone to disease exacerbation when treatment is delayed due to COVID-19, especially those with incomplete lesion clearance.

Objective:To report a case of tuberous sclerosis complex complicated by acne inversa, and to analyze gene variations.Methods:Peripheral blood samples were collected from a female patient with tuberous sclerosis complex complicated by acne inversa, her younger brother, and her parents. Exome sequencing was performed to detect gene variations in the patient, and Sanger sequencing to confirm the pathogenic gene mutations.Results:The patient clinically presented with facial angiofibromas, ash-leaf macules, and shagreen patches, as well as multiple cutaneous comedones, nodules, abscesses, and scars. The paitent also had epilepsy and multiple renal cysts. The initial diagnosis was tuberous sclerosis complex complicated by acne inversa. Genetic testing for the patient revealed a heterozygous frameshift mutation c.3506dupC (p.A1169fs) in the TSC2 gene and a heterozygous nonsense mutation c.123T>G (p.Y41X) in the NCSTN gene. The heterozygous nonsense mutation c.123T>G (p.Y41X) was also identified in the patient's younger brother and mother, while neither of the above mutations were identified in the patient's father or 100 unrelated healthy controls. The above mutations were also not retrieved in the ClinVar, ExAC and 1000 Genomes databases.Conclusion:The mutation c.3506dupC in the TSC2 gene and mutation c.123T>G in the NCSTN gene may be responsible for the unique clinical manifestations in the patient, and the mutation c.3506dupC may potentially exacerbate the phenotype of acne inversa through the mTORC1 pathway.

Objective:To report a case of tuberous sclerosis complex complicated by acne inversa, and to analyze gene variations.Methods:Peripheral blood samples were collected from a female patient with tuberous sclerosis complex complicated by acne inversa, her younger brother, and her parents. Exome sequencing was performed to detect gene variations in the patient, and Sanger sequencing to confirm the pathogenic gene mutations.Results:The patient clinically presented with facial angiofibromas, ash-leaf macules, and shagreen patches, as well as multiple cutaneous comedones, nodules, abscesses, and scars. The paitent also had epilepsy and multiple renal cysts. The initial diagnosis was tuberous sclerosis complex complicated by acne inversa. Genetic testing for the patient revealed a heterozygous frameshift mutation c.3506dupC (p.A1169fs) in the TSC2 gene and a heterozygous nonsense mutation c.123T>G (p.Y41X) in the NCSTN gene. The heterozygous nonsense mutation c.123T>G (p.Y41X) was also identified in the patient's younger brother and mother, while neither of the above mutations were identified in the patient's father or 100 unrelated healthy controls. The above mutations were also not retrieved in the ClinVar, ExAC and 1000 Genomes databases.Conclusion:The mutation c.3506dupC in the TSC2 gene and mutation c.123T>G in the NCSTN gene may be responsible for the unique clinical manifestations in the patient, and the mutation c.3506dupC may potentially exacerbate the phenotype of acne inversa through the mTORC1 pathway.

Objective:To construct a follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019), and provide a reference basis for the next revision and improvement of the standard.Methods:The evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) was preliminarily established by consulting relevant references and materials. The experts in the field of diagnosis, treatment, prevention and control of brucellosis were selected, and two rounds of expert consultation were carried out in the form of questionnaires using the Delphi method. The necessity and availability of evaluation indicators were scored, and suggestions for modifying and adding indicators were put forward. Based on this, a standard follow-up evaluation index system was established. At the same time, a judgment matrix was constructed combined with the Saaty scale, and the analytic hierarchy process was used to calculate the weight of each index in the system.Results:After 2 rounds of expert ( n = 10) consultation, a standard follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) was constructed with 3 first-level indexes, 8 second-level indexes and 21 third-level indexes. The positive coefficients of experts in 2 rounds of questionnaires were both 100%; the coefficient of authority of experts was 0.82; the Kendall's coefficients of concordance of first-level, second-level and third-level indexes were 0.722, 0.260, and 0.181, respectively, with P < 0.05. Among the first-level indexes, the weight of standard quality evaluation was the highest (0.364), and the weight of standard implementation status was the lowest (0.278); among the second-level indexes, the combined weight of social benefits was the highest (0.186), and the combined weight of advanced nature was the lowest (0.043); among the third-level indexes, the combined weight of timely diagnosis rate was the highest (0.096), and the combined weight of consistency with technical data was the lowest (0.009). Conclusions:The constructed follow-up evaluation index system for "Diagnosis of Brucellosis" (WS 269-2019) is scientific and reliable, which evaluated qualitatively and quantitatively, reduces the defects of a single evaluation, and provides a basis for subsequent revision and improvement of the standard.

Objective:To analyze the epidemiological characteristics and related indicators of plague in Yulin City, Shaanxi Province, and to evaluate the risk of plague epidemic in the future and formulate scientific and reasonable prevention and control measures.Methods:The plague surveillance data of national (Dingbian County) and provincial (Yuyang District, Jingbian County, Hengshan District, Shenmu City, Fugu County) plague monitoring sites in Yulin City from 2011 to 2021 were collected through the China Disease Prevention and Control Information System Pestis Prevention and Control Management Information System, and the plague epidemic situation among humans and animals, the main host animals and their flea infection were analyzed by descriptive epidemiological methods. The expert consultation method and plague risk assessment tool V1.0 were used to assess the epidemic risk of the plague in Yulin City.Results:There was no human and animal plague epidemic in Yulin City from 2011 to 2021. In national monitoring site, the density of main host animal was 5.79/hm 2, ranging from 3.02/hm 2 to 9.08/hm 2,the dominant species was Mongolian gerbil, accounting for 98.21% (3 402/3 464); the capture rate of wild nocturnal rodents was 1.27% (350/27 600), ranging from 0.21% to 3.83%, the dominant species was Cricetulus barabensis, accounting for 44.86% (157/350); the flea infection rate of the rodent body was 16.91% (768/4 541), with a flea index of 0.40, the dominant flea species was the Nosopsyllus laeviceps kuzenkov, accounting for 66.54% (1 203/1 808). In provincial monitoring site, the density of main host animals was 0.49/hm 2, ranging from 0.31/hm 2 to 0.67/hm 2, the dominant species was Alashan ground squirrel, accounting for 63.61% (194/305); the capture rate of nocturnal rodents in the wild was 1.76% (560/31 795), ranging from 0.89% to 3.93%, the dominant species was Roborovski dwarf hamster, accounting for 26.61% (149/560); the capture rate of domestic rats was 2.37% (397/16 750), ranging from 1.48% to 3.10%, the rodents included Rattus norvegicus (47.36%, 188/397) and house mouse (52.64%, 209/397); the flea infection rate of the rat body was 13.26% (182/1 373), with a flea index of 0.40; the dominant flea species was Ophthalmopsylla jettmari, accounting for 45.23% (251/555). The 5 281 pathogenic culture samples and 2 110 serological test samples were all negative. The Pearson correlation analysis results showed that there was no correlation between rodent density and flea infection rate or flea index at national and provincial monitoring sites ( r = - 0.26, - 0.48, 0.09, 0.12, P > 0.05), while flea infection rate and flea index were positively correlated ( r = 0.67, 0.81, P < 0.05). In 2022, Yulin City, Shaanxi Province was not ruled out the possibility of human plague epidemic, and the risk of plague epidemic among animals was high. Conclusions:From 2011 to 2021, the density of the main host animals at the national and provincial monitoring sites in Yulin City has remained at a low level, and the flea index has increased. There is a risk of plague epidemic in Yulin City, so the monitoring work should be further strengthened, and emergency supplies and capacity reserves should be well prepared.