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.

Cerebral ischemia-reperfusion injury can lead to secondary brain damage through com-plex pathological processes such as ion imbalance,inflammation,mitochondrial dysfunction,oxidative stress,and increased vascular permeability,serious-ly affecting the prognosis and quality of life of isch-emic stroke patients.How to effectively reduce and prevent neurological damage caused by CIRI has become a key and hot topic in CIS research.In re-cent years,many studies have confirmed that the active ingredients of traditional Chinese medicine can alleviate oxidative stress,inhibit autophagy,regulate cell apoptosis,control neuroinflammation,reduce cell apoptosis index,alleviate neuronal his-topathological damage,promote neuronal survival,enhance synaptic plasticity,and play a therapeutic role in CIRI through the PI3K/Akt signaling pathway.In summary,this article provides a review of the PI3K/Akt signaling pathway and its role in CIRI,as well as the research on the regulation of PI3K/Akt signaling by active ingredients in traditional Chi-nese medicine for the treatment of CIRI.The aim is to provide a theoretical basis for the clinical use of active ingredients in traditional Chinese medicine to alleviate CIRI damage.

BACKGROUND:The elastic modulus of traditional solid titanium alloy implants is higher than that of human bone,and the resulting"stress shielding"phenomenon may affect the osseointegration of implants.Simultaneously,the wettability of 3D printed titanium alloy surface needs to be improved.OBJECTIVE:To prepare hydrophilic Gyroid implants with excellent biomechanical properties.METHODS:The 3D models of Gyroid implant,solid implant,mandibular bone and crown were established,and the mechanical properties of different implants were analyzed by finite element analysis.The Gyroid structure implant model was imported into the 3D printer to make the Gyroid structure implant materialized,and then the hydrophilic Gyroid structure implant with excellent mechanical properties and surface activity was prepared by sandblasting acid etching and ultraviolet functionalization.The morphology and hydrophilicity of 3D printed Ti6Al4V specimens before and after surface modification were analyzed by scanning electron microscopy and contact angle test.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that under the vertical average bite force,the Gyroid structure could uniformly disperse the load acting on the implant into the entire structure.The load on the solid structure implant could only be dispersed on its outer surface and concentrated in the neck.The maximum equivalent stress of the Gyroid structure implant was 200.67 MPa,which did not exceed 50%of the yield strength of Ti6Al4V material.The maximum equivalent stress of the Gyroid structure implant on the surrounding bone tissue was 24.27 MPa,which was slightly higher than the maximum equivalent stress of the solid structure implant 17.32 MPa,and in the range of 20-60 MPa.The stimulation effect of the Gyroid structure implant on new bone formation was better than that of the solid structure implant.(2)The 3D printing technology could materialize the Gyroid structure implant model.Scanning electron microscopy showed that there were many unmelted spherical metal particles on the surface of the 3D printed Ti6Al4V specimens.After sandblasting and acid etching,a micron-scale mesh pore structure was formed on the surface,and no protruding metal particles were seen.The surface morphology of the superimposed UV functional treatment group was basically consistent with that after sandblasting and acid etching.The contact angle test results showed that the surface hydrophilicity of the specimens treated with ultraviolet functionalization plus sandblasting and acid etching was better than that of the sandblasting and acid etching and non-surface treatment groups.(3)The sandblasting and acid etching technology can remove the weakly connected metal particles on the 3D printed specimen and improve the similarity between the solid model and the design model.On this basis,the ultraviolet functionalization treatment can significantly improve the hydrophilicity of the 3D printed Gyroid structure implant surface without affecting its structure.

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.

Cerebral ischemia-reperfusion injury can lead to secondary brain damage through com-plex pathological processes such as ion imbalance,inflammation,mitochondrial dysfunction,oxidative stress,and increased vascular permeability,serious-ly affecting the prognosis and quality of life of isch-emic stroke patients.How to effectively reduce and prevent neurological damage caused by CIRI has become a key and hot topic in CIS research.In re-cent years,many studies have confirmed that the active ingredients of traditional Chinese medicine can alleviate oxidative stress,inhibit autophagy,regulate cell apoptosis,control neuroinflammation,reduce cell apoptosis index,alleviate neuronal his-topathological damage,promote neuronal survival,enhance synaptic plasticity,and play a therapeutic role in CIRI through the PI3K/Akt signaling pathway.In summary,this article provides a review of the PI3K/Akt signaling pathway and its role in CIRI,as well as the research on the regulation of PI3K/Akt signaling by active ingredients in traditional Chi-nese medicine for the treatment of CIRI.The aim is to provide a theoretical basis for the clinical use of active ingredients in traditional Chinese medicine to alleviate CIRI damage.

BACKGROUND:The elastic modulus of traditional solid titanium alloy implants is higher than that of human bone,and the resulting"stress shielding"phenomenon may affect the osseointegration of implants.Simultaneously,the wettability of 3D printed titanium alloy surface needs to be improved.OBJECTIVE:To prepare hydrophilic Gyroid implants with excellent biomechanical properties.METHODS:The 3D models of Gyroid implant,solid implant,mandibular bone and crown were established,and the mechanical properties of different implants were analyzed by finite element analysis.The Gyroid structure implant model was imported into the 3D printer to make the Gyroid structure implant materialized,and then the hydrophilic Gyroid structure implant with excellent mechanical properties and surface activity was prepared by sandblasting acid etching and ultraviolet functionalization.The morphology and hydrophilicity of 3D printed Ti6Al4V specimens before and after surface modification were analyzed by scanning electron microscopy and contact angle test.RESULTS AND CONCLUSION:(1)The finite element analysis results showed that under the vertical average bite force,the Gyroid structure could uniformly disperse the load acting on the implant into the entire structure.The load on the solid structure implant could only be dispersed on its outer surface and concentrated in the neck.The maximum equivalent stress of the Gyroid structure implant was 200.67 MPa,which did not exceed 50%of the yield strength of Ti6Al4V material.The maximum equivalent stress of the Gyroid structure implant on the surrounding bone tissue was 24.27 MPa,which was slightly higher than the maximum equivalent stress of the solid structure implant 17.32 MPa,and in the range of 20-60 MPa.The stimulation effect of the Gyroid structure implant on new bone formation was better than that of the solid structure implant.(2)The 3D printing technology could materialize the Gyroid structure implant model.Scanning electron microscopy showed that there were many unmelted spherical metal particles on the surface of the 3D printed Ti6Al4V specimens.After sandblasting and acid etching,a micron-scale mesh pore structure was formed on the surface,and no protruding metal particles were seen.The surface morphology of the superimposed UV functional treatment group was basically consistent with that after sandblasting and acid etching.The contact angle test results showed that the surface hydrophilicity of the specimens treated with ultraviolet functionalization plus sandblasting and acid etching was better than that of the sandblasting and acid etching and non-surface treatment groups.(3)The sandblasting and acid etching technology can remove the weakly connected metal particles on the 3D printed specimen and improve the similarity between the solid model and the design model.On this basis,the ultraviolet functionalization treatment can significantly improve the hydrophilicity of the 3D printed Gyroid structure implant surface without affecting its structure.

Objective:To investigate the clinical characteristics of psoriasis and status quo of medical care for patients in county areas of China.Methods:This study was a cross-sectional investigation. Based on the “Qianxian Wuyin” Project (a national project for upgrating ability for psoriasis care at county level), an online questionnaire survey was conducted in the dermatology departments of 459 county hospitals in 404 pilot administrative counties across China from February to June 2023. The questionnaire included demographic information of patients (gender, ethnicity, age, place of residence, education, marital status), and clinical characteristics of psoriasis (disease course, type, comorbidities, body surface area (BSA) and previous treatment. The Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were applied for assessing the quality of life and disease severity, and completed by patients or guardian and doctors, respectively.Results:A total of 16 935 patients completed the questionnaire. The age of patients was 1-102(44.17±11.58)years, and 71.0% (12 036/16 935) were 30-59 years old. The ratio of male to female was 2.21∶1; 24.3%(4 117/16 935) of patients had high school education; there were 9 940 patients(58.7%) with previous or current smoking and/or alcohol use; 42.8%(7 218/16 855) of patients had a disease course of 1-5 years. There were 15 630 patients(92.3%) with DLQI≥10, 8 346 patients(49.7%) with PASI≥10, 15 017 patients(89.2%) with BSA≥10%. The plaque type was the most common disease type ( n=14 965, 88.7%), and spotting type ranked the second ( n=1 141, 6.8%). The most common initial site was the trunk ( n=12 309, 72.9%). Among the comorbidities, hypertension was the most common one ( n=1 681, 10.0%). There were 7 650 reports of treatment response to conventional topical drug therapy and 3 112 reports of treatment response to systemic drug therapy, with 6 269 (81.9%) and 2 493 (80.1%) reporting poor or no response, respectively. Conclusions:The survey shows that in the county areas of China, the majority of psoriasis patients are severe patients with short course of disease, plaque type is the most common type, and hypertension is the most common comorbidity; and the conventional treatment is less effective for most patients.

Objective:To explore the relationship between gene mutation in the pre-C region of hepatitis B virus (HBV) and acute-on-chronic liver failure (ACLF) associated with hepatitis B.Methods:Fifty-eight patients with chronic hepatitis B (CHB) admitted to the General Hospital of Northern Theater Command of the Chinese People′s Liberation Army from May 2020 to May 2023 were selected as the CHB group, 51 patients with chronic hepatitis B liver cirrhosis (CHB-LC) were selected as the CHB-LC group, and 52 patients with hepatitis B-related acute-on-chronic liver failure were selected as the ACLF group. The clinicopathological data of the three groups were collected for retrospective analysis. Peripheral serum HBV DNA of the three groups was collected. The pre-C region genes of HBV in the three groups were amplified by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR), and then gene sequencing was performed. The variation at position 1896 of the pre-C region gene of HBV in the three groups was recorded. The general data, hepatitis B e antigen (HBeAg), HBV DNA quantification, triglycerides (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and gene mutation in the pre-C region of the three groups were observed and compared. Logistic regression analysis was performed on the related influencing factors of the onset of hepatitis B-related ACLF.Results:There were no statistically significant differences in gender, age, disease course, body mass index (BMI), TG, TC, and BUN among the three groups (all P>0.05), and there were statistically significant differences in HBeAg, HBV DNA quantification, ALT, and AST among the three groups (all P<0.05). The HBV DNA quantification, ALT, and AST in the ACLF group were higher than those in the CHB group and the CHB-LC group (all P<0.05). The mutation rate at position 1896 of the pre-C region gene of HBV in the ACLF group was higher than that in the CHB group and the CHB-LC group (all P<0.05); The results of logistic multivariate regression analysis showed that HBV DNA quantification, ALT, and gene mutation in the pre-C region were independent influencing factors for the onset of hepatitis B-related ACLF ( OR=1.042, 1.570, 1.413, P<0.05). Conclusions:The variation at position 1896 of the pre-C region gene of HBV is common in patients with HBV infection at different disease courses. The incidence of its variation shows a gradually increasing trend in CHB, CHB-LC, and ACLF. Elevated HBV DNA and ALT and gene mutation in the pre-C region of HBV are independent risk factors for the occurrence of hepatitis B-related ACLF. The progress of the disease in such patients requires clinical attention.

Abstract OBJECTIVE To study the effect of berberine(BBR) on autophagy of human breast cancer HCC1937 cells under hypoxia condition. METHODS Cultured human breast cancer HCC1937 cells, CCK-8 method was used to determine the effects of different concentrations of BBR(0, 5, 10, 20, 40, 80, 160 μmol·L-1) on cell viability under normoxia and hypoxia conditions, and select the drug concentration for further experiments. Cultured HCC1937 cells were randomly divided into 4 groups: control group, 20 μmol·L-1 BBR group, hypoxia group, hypoxia+20 μmol·L-1 BBR group. LIVE/DEAD cell viability/cytotoxicity kits were used to measure the cell death rate. The expressions of autophagy related proteins Beclin1, LC3 and P62 in each group were determined by Western blotting. The cells were infected with mCherry-GFP-LC3 adenovirus, and the number of autophagosomes and autophagolysosomes in each group were counted by laser confocal microscopy to determine the effect of BBR on the autophagy flow of HCC1937 cells. RESULTS BBR decreased the cell viability of human breast cancer HCC1937 cells in a concentration-dependent manner. After hypoxia treatment, the cell death rate of HCC1937 cells was not significantly changed, and the intracellular Beclin1, LC3-II and LC3-II/LC3-I ratio were significantly increased, while P62 without significant changes, and the autophagy flow was increased. BBR significantly increased cell death rate, decreased Beclin1 and LC3II/LC3-I ratio, increased intracellular P62, significantly reduced the number of autophagosomes and autophagolysosomes, and inhibited the formation and clearance of autophagosomes under both normal and hypoxia conditions. CONCLUSION BBR increases the death rate of human breast cancer HCC1937 cells under hypoxia condition, and its effect is related to the inhibitory effect of berberine on autophagy under hypoxia condition.