Objective To investigate the effect and mechanism of actin gamma1(ACTG1)downregulation on apoptosis in gastric cancer cells line HGC-27.Methods Stable ACTG1 knockdown HGC-27 cell line was constructed by CRISPR/Cas9,ACTG1 knockdown was verified by DNA sequencing and Western blot,apoptosis rate was detected by flow cytometry,Western blot detected the expression level of apoptosis-related proteins Bcl2-associated X protein(Bax),B cell lymphoma 2 family protein(Bcl2)and PI3K/AKT signal pathway-related proteins AKT and p-AKT.Results HGC-27 cell lines with stable knockdown of ACTG1 were constructed,and the ACTG1 protein levels were decreased in the sgACTG1-1 and sgACTG1-2 groups compared with the Control group.Compared with the apoptosis rate in the Control group(6.54%±0.67%),cell apoptosis rate in the sgACTG1-1 and sgACTG1-2 groups(10.11%±0.46%,14.67%±0.17%)were significantly increased,the differences were statistically significant(t=-7.58,-20.28,all P<0.01).Compared the Control group,the Bax protein levels in the sgACTG1-1 and sgACTG1-2 groups(0.89±0.02,1.00±0.08 vs 0.71±0.03)were significantly increased(t=-8.14,-5.87),the level of Bcl2 protein(0.49±0.06,0.39±0.06 vs 0.65±0.07)were significantly decreased(t=3.09,5.35),the differences were statistically significant(all P<0.05).Compared with the Control group,the AKT protein levels in the sgACTG1-1 and sgACTG1-2 groups(0.95±0.10,0.43±0.09 vs 1.17±0.06)and the P-AKT protein level(0.38±0.08,0.28±0.12 vs 0.70±0.14)were significantly decreased,the differences were statistically significant(t=3.20,12.13;3.44,3.85,all P<0.05).Conclusion Downregulation of ACTG1 inhibits the expression of PI3K/Akt signaling pathway related proteins AKT,p-AKT and promotes gastric cancer cells line HGC-27 apoptosis.

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 investigate the effect and mechanism of actin gamma1(ACTG1)downregulation on apoptosis in gastric cancer cells line HGC-27.Methods Stable ACTG1 knockdown HGC-27 cell line was constructed by CRISPR/Cas9,ACTG1 knockdown was verified by DNA sequencing and Western blot,apoptosis rate was detected by flow cytometry,Western blot detected the expression level of apoptosis-related proteins Bcl2-associated X protein(Bax),B cell lymphoma 2 family protein(Bcl2)and PI3K/AKT signal pathway-related proteins AKT and p-AKT.Results HGC-27 cell lines with stable knockdown of ACTG1 were constructed,and the ACTG1 protein levels were decreased in the sgACTG1-1 and sgACTG1-2 groups compared with the Control group.Compared with the apoptosis rate in the Control group(6.54%±0.67%),cell apoptosis rate in the sgACTG1-1 and sgACTG1-2 groups(10.11%±0.46%,14.67%±0.17%)were significantly increased,the differences were statistically significant(t=-7.58,-20.28,all P<0.01).Compared the Control group,the Bax protein levels in the sgACTG1-1 and sgACTG1-2 groups(0.89±0.02,1.00±0.08 vs 0.71±0.03)were significantly increased(t=-8.14,-5.87),the level of Bcl2 protein(0.49±0.06,0.39±0.06 vs 0.65±0.07)were significantly decreased(t=3.09,5.35),the differences were statistically significant(all P<0.05).Compared with the Control group,the AKT protein levels in the sgACTG1-1 and sgACTG1-2 groups(0.95±0.10,0.43±0.09 vs 1.17±0.06)and the P-AKT protein level(0.38±0.08,0.28±0.12 vs 0.70±0.14)were significantly decreased,the differences were statistically significant(t=3.20,12.13;3.44,3.85,all P<0.05).Conclusion Downregulation of ACTG1 inhibits the expression of PI3K/Akt signaling pathway related proteins AKT,p-AKT and promotes gastric cancer cells line HGC-27 apoptosis.

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 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.

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.