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 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.

A 3-year-old male patient was diagnosed with neurofibromatosis type 1(NF1) for two years. The patient has multiple neurofibromas in retroperitoneum, lumbococcygeal paravertebral, lumbosacral spinal canal, and foramina. Due to retroperitoneal mass compression, the child suffered from urological complications such as hydronephrosis, ureterdilation, neurogenic bladder, etc., which seriously affected the urination function and resulted in multiple surgical treatments. Currently, the patient has been treated with mitogen activates extracelluar signal-regulated kinases(MEK) inhibitor selumetinib targeted therapy, and has voluntarily urinated, and his general state is better than before medication. The diagnosis and treatment of this case reflects the importance of multidisciplinary collaboration in the diagnosis and treatment of rare diseases.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Objective To investigate the association and difference between patent foramen ovale(PFO), atrial septal aneurysm(ASA), atrial septal defect(ASD) in normal controls and cryptogenic ischemic stroke(CS) in youth diagnosed by double source CT.Methods A total of 168 CS patients and 180 controls matched age and gender were included in the present study.The two groups were diagnosed by double source CT and clinical materials.The incident rate of PFO, ASA, ASD, the degrees of PFO, ASD,the lengths of PFO and difference between CS in two groups were analysed.Results The incident rates of PFO, ASA, ASD were 40.6%,10.7%,6.5% and 15.6%,3.3%,2.2% in CS groups and controls respectively(P<0.001).The incident rates of PFO merged ASA and ASA merged ASD were 6.0%,3.0% and 0%,0% respectively between two groups(P<0.001).The diameters of PFO, ASD were (1.71±0.62) mm,(3.42±0.72) mm and (0.85±0.51) mm,(2.45±0.42) mm in two groups respectively(P<0.001).The lengths of PFO were (14.6±3.8) mm and (8.2±2.3) mm in two groups(P<0.001).The correlations between stroke in two groups were no difference(P>0.001).Conclusion PFO,ASA and ASD are important to CS.While PFO,ASA and ASD can accurately be diagnosed by double source CT.

1,2,4-Butanetriol (BT) is an important non-natural chemical with a variety of industrial applications. A recombinant Escherichia coli biosynthesizing BT from D-xylose was constructed by heterologously expressing xdh and mdlC, and knocking out competing pathway genes including xylA, xylB, yjhE, yagH and ycdW. To optimize BT synthesis pathway, the third catalytic step that catalyzes the decarboxylation reaction of 3-deoxy-D-glycero-pentulosonic acid was identified as a potential bottleneck. Consequently, 2-keto acid decarboxylases from three different microorganisms were screened, and the kivD gene from Lactococcus lactis was found to increase BT titer by 191%. The improved strain BW-025 reached a final BT titer of 2.38 g/L under optimized transformation conditions. Attempts on synthetic pathway optimization were also made by fine-tuning the expression levels of each enzyme involved in the whole pathway based on BW-025. As a result, an xdh overexpressed recombinant strain, BW-074 was finally generated, with 48.62% higher BT production than that of BW-025.
Butanols ; metabolism ; Escherichia coli ; metabolism ; Gene Knockout Techniques ; Genetic Engineering ; Industrial Microbiology ; methods ; Metabolic Networks and Pathways

Objective To investigate the characteristics and risk factors for allogeneic transfusion after unilateral total knee arthroplasty (TKA).Methods 852 patients (663 female and 189 male) underwent primary unilateral TKA from January 2014 to December 2014 were included.Average age of included patients were 64.9±7.9 years old (22-87).829 patients were osteoarthritis,others rheumatoid arthritis.The ASA score,BMI,doctor groups,diabetes,hypertension,thrombus (duplex color Doppler ultrasonography),pre-HGB,pre-HCT,pre-TP,pre-Cr,pre-BUN,pre-PT,operation time,starting MABP of the operation,anesthesia and TXA were collected.Potential risk factors for allogeneic transfusion were analyzed statistically via univariate and multivariate regression analysis.Results The preoperative hemoglobin level in 71 (8.3％) patients were lower than that in normal (male ＜120 g/L,female ＜110 g/L).The hematokrit in 27 (3.2％) patients were lower than that in normal (male ＜40％,female ＜37％).TXA was used in 740 (86.9％) patients during the operation.Allogeneic transfusion was performed in 202 (23.7％) the patients after TKA.The differences in the following items within two groups were statistically significant via univariate analysis (P＜0.05),female and male,≥70 and ＜ 70 years,pre-HGB normal and low,pre-HCT normal and low and with and without TXA.Female [OR=2.283,95％CI (1.405,3.711)],patient age of 70 years or older [OR=2.048,95％CI (2.064,4.292)],preoperative hemoglobin level low [male ＜ 120 g/L,female ＜ 110 g/L,OR=1.506,95％CI (1.376,4.427)] and preoperative hematokrit below normal [male ＜ 40％,female ＜ 37％,OR=3.412,95％CI (1.086,6.591)] were independent predictors for postoperative allogeneic transfusion in multivariate regression analysis.Conclusion The allogeneic transfusion rate after unilateral TKA was 23.7％.Female,older than 70 years and preoperative anemia were independent predictors for postoperative allogeneic transfusion after TKA.TXA can effectively decrease the postoperative allogeneic transfusion rate and the amount of transfusion.

Objective To evaluate the additional efficacy of local anesthetic injection (LAI) as a part of multimodal anal?gesia in patients undergoing total knee arthroplasty (TKA) with respect to pain, narcotic use, knee function and complications. Methods A multicenter randomized, controlled, double blind study was performed. A total of 101 patients undergoing unilateral TKA in two centers were randomly divided into injection group and control group. Injection group (50 cases) received local anes?thetic injection of ropivacaine (200 mg), fentanyl (1μg) and epinephrine (1∶1 000, 0.25 mg) in operation and control group (51 cas?es) did not. All patients received standardized general anesthesia and postoperative intravenous patient controlled analgesia (PCA). Preoperative baseline data, surgery?related conditions, postoperative pain (on a 0 to 10 scale), knee function, time of open?ing PCA, narcotic dosage in PCA and complications were compared respectively. Results The time of opening PCA in injection group (4-10 h, M=8 h) was longer than that in control group (2-5 h, M=4 h) (P<0.05). The 12 h, 24 h and total narcotic use of PCA in injection group (8.62±3.601 ml, 21.22±9.220 ml, 38.52±7.764 ml) was less than that in control group (18.43±9.671 ml, 35.30± 11.414 ml, 55.52±12.405 ml) (P<0.05). At post anesthesia care unit the mean VAS in injection group (2.40±1.927) was lower than that in control group (3.06 ± 2.073) (P<0.05). There was no difference in mean VAS at other time points, knee function, length of stay between two groups (P>0.05). Conclusion LIA in TKA can relieve pain early after TKA, prolong the time of opening PCA and reduce narcotic use compared with patients without it. It is simple and safe to use.

Objective To observe the effects of tumor necrosis factor-or (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2-/-) mice and explore related mechanisms.Methods Mice of control group,MMP9-/-group,MMP2-/-group and MMP9/2-/-group were studied.Femoral artery was injured by transluminal wire,the mRNA expression levels of TNF-o and PDGF on femoral artery were detected by RT-PCR;the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0,1,3,7,14and 28 post injury.Mice in control group received TNF-α(5 ng/ml,0.10 ml),TNF-α(0.05 ml) + MMP inhibitor SB-3CT (0.50 ng/ml,0.05 ml) injection,or PDGF-bb (10 ng/ml,0.10 ml) and PDGF-bb (0.05 ml) + SB-3CT(0.05 ml) injection around injured artery,intimal hyperplasia at 2 and 4 weeks after injury was observed.Intimal hyperplasia at 2 and 4 weeks after injury was also observed in MMP9/2-/-mice.TNF-α(5 ng/ml,0.10 ml) was injected to MMP2-/-mice,PDGF-bb (0.1 ml) was injected to MMP9-/-mice around injured artery,intimal hyperplasia at 2 and 4 weeks after injury was observed.The degree of neointimal hyperplasia were observed by the Elastica-van Gieson staining and the area of neointima and media of the arteries were measured by SigmaPlot and intima ratio was calculated.Vascular smooth muscle cell (VSMC) mediums of MMP9-/-and MMP2-/-mice were stimulated by TNF-α and PDGF-bb,respectively,and migration assay,and proliferation assay were performed,relative migration and proliferation cells numbers were counted.Results (1) mRNA expression of TNF-o (235.33 ± 23.68) and PDGF-bb (3.30 ±0.56) in femoral arteries peaked at 1 day after injury,while MMP9 or MMP2 protein expression peaked at 7 or 28 days after injury.(2) In control mice,TNF-α intervention significantly enhanced intimal hyperplasia at 2 weeks after injury (2.21 ±0.05 vs.1.55 ±0.03 in blank control group,P ＜ 0.05),while PDGF-bb intervention significantly enhanced intimal hyperplasia at 4 weeks after injury (2.60 ± 0.07 vs.1.89 ± 0.04,P =0.03).(3) Intima hyperplasia was significantly higher in control group than in MMP9/2-/-group at 2 weeks (1.63 ± 0.05 vs.0.46 ± 0.01,P =0.008) and 4 weeks (2.24 ±0.06 vs.0.51 ±0.01) after injury(P =0.005).(4) TNF-o intervention stimulated intimal hyperplasia in MMP2-/-mice (intimal ratio at 2 weeks after injury:1.73 ± 0.05 vs.1.23 ± 0.03,P =0.02) and PDGF-bb intervention stimulated intimal hyperplasia in MMP9-/-mice(intimal ratio at 4 weeks after injury:2.32 ± 0.06 vs.1.35 ± 0.03,P =0.03).(5) Reduced VSMC migration was evidenced in MMP9-/-mice post TNF-α stimulation (1.45 ±0.03 vs.2.16 ±0.04 in control group,P =0.03),while reduced VSMC proliferation post PDGF was seen in MMP2-/-group (1.15 ± 0.02 vs.1.82 ± 0.04 in control group,P =0.03).Conclusions TNF-o induced MMP9 activation plays a major role on promoting VSMC migration at the first 2 weeks after vascular injury,while PDGF induced MMP2 activation plays a crucial role on VSMC proliferation on the following 2 weeks after vascular injury in this mice model.Thus,the axis of TNF-α-MMP9-VSMC migration axis and PDGF-MMP2-VSMC proliferation axis are the two major working mechanisms responsible for intimal hyperplasia post vascular injury.