We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective:To evaluate the efficacy and safety of anaprazole (40 mg and 60 mg) and compared with rabeprazole (20 mg) in the treatment of reflux esophagitis (RE).Methods:This multicenter, randomized, double-blinded, positive drug parallel controlled study was led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) and a total of 24 clinical trial institutions nationwide including the First Affiliated Hospital of Nanchang University, Yichun People′s Hospital, Meihekou Central Hospital, the First Affiliated Hospital of Gannan Medical University, and Jinhua Central Hospital, participated in this research. A total of 156 patients with RE (Los Angeles grade A to D) were enrolled and randomly divided into 3 groups, anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group, using a random number table in a ratio of 1∶1∶1. Patients in the above 3 groups were treated with the appropriate trial medication once per day for 4 or 8 weeks. The endoscopic healing rates were evaluated by Blinded Independent Central Review (BICR) and investigators. In addition, the improvement in the severity of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) and medication safety were also evaluated. The endoscopic healing rates and 95% confidence intervals (95% CI) at week-8 and -4 were calculated by groups, as well as the difference in the healing rates and their 95% CI among groups. The chi-square test was used for statistical analysis. Results:A total of 153 subjects were included in the full analysis set (FAS), 144 in the per-protocol analysis set (PPS) and 151 in the safety set (SS). In the FAS, after 8 weeks of treatment, the endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly assessed by BICR were 86.0% (43/50), 86.5% (45/52) and 86.3% (44/51), respectively, and the 95% CI were 76.4% to 95.6%, 77.3% to 95.8% and 76.8% to 95.7%, respectively.The endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly evaluated by investigators were 88.0% (44/50), 90.4% (47/52) and 86.3% (44/51), respectively, and the 95% CI were 79.0% to 97.0%, 82.4% to 98.4% and 76.8% to 95.7%, respectively. The endoscopic healing rates were similar among groups. In the FAS, the differences in healing rates(95% CI) assessed by BICR and investigators between anaprazole 40 mg, anaprazole 60 mg and rabeprazole 20 mg group were -0.3%(-13.7% to 13.2%), 0.6%(-12.3% to 13.6%), respectively and 1.7%(-11.3% to 14.8%), 3.9%(-8.5% to 16.3%), respectively. The results of the PPS were consistent with those of the FAS. After 8 weeks of treatment, the severity scores of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) decreased in all groups. The differences between post-treatment and baseline in anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were -1.54±1.00, -1.91±1.00, -1.51±0.76, -1.45±0.71; -1.30±0.94, -1.59±0.96, -1.33±0.65, -1.42±0.60; and -1.74±0.85, -1.76±0.93, -1.45±0.66, -1.66±0.79, respectively. The incidence of treatment emergent adverse event of anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were 57.1% (28/49), 48.1% (25/52) and 60.0% (30/50), respectively, and the incidence of treatment related adverse event were 18.4% (9/24), 25.0% (13/52) and 24.0% (12/50), respectively. There were no statistically significant differences in the incidence of treatment emergent adverse event and treatment related adverse event among 3 groups (all P>0.05). Conclusion:The efficacy and safety of anaprazole 40, 60 mg/d, and rabeprazole 20 mg/d in the treatment of RE are comparable.

Objective:To evaluate the efficacy and safety of anaprazole (40 mg and 60 mg) and compared with rabeprazole (20 mg) in the treatment of reflux esophagitis (RE).Methods:This multicenter, randomized, double-blinded, positive drug parallel controlled study was led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) and a total of 24 clinical trial institutions nationwide including the First Affiliated Hospital of Nanchang University, Yichun People′s Hospital, Meihekou Central Hospital, the First Affiliated Hospital of Gannan Medical University, and Jinhua Central Hospital, participated in this research. A total of 156 patients with RE (Los Angeles grade A to D) were enrolled and randomly divided into 3 groups, anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group, using a random number table in a ratio of 1∶1∶1. Patients in the above 3 groups were treated with the appropriate trial medication once per day for 4 or 8 weeks. The endoscopic healing rates were evaluated by Blinded Independent Central Review (BICR) and investigators. In addition, the improvement in the severity of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) and medication safety were also evaluated. The endoscopic healing rates and 95% confidence intervals (95% CI) at week-8 and -4 were calculated by groups, as well as the difference in the healing rates and their 95% CI among groups. The chi-square test was used for statistical analysis. Results:A total of 153 subjects were included in the full analysis set (FAS), 144 in the per-protocol analysis set (PPS) and 151 in the safety set (SS). In the FAS, after 8 weeks of treatment, the endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly assessed by BICR were 86.0% (43/50), 86.5% (45/52) and 86.3% (44/51), respectively, and the 95% CI were 76.4% to 95.6%, 77.3% to 95.8% and 76.8% to 95.7%, respectively.The endoscopic healing rates of anaprazole 40 mg group, anaprazde 60 mg group and raberazole 20 mg group blindly evaluated by investigators were 88.0% (44/50), 90.4% (47/52) and 86.3% (44/51), respectively, and the 95% CI were 79.0% to 97.0%, 82.4% to 98.4% and 76.8% to 95.7%, respectively. The endoscopic healing rates were similar among groups. In the FAS, the differences in healing rates(95% CI) assessed by BICR and investigators between anaprazole 40 mg, anaprazole 60 mg and rabeprazole 20 mg group were -0.3%(-13.7% to 13.2%), 0.6%(-12.3% to 13.6%), respectively and 1.7%(-11.3% to 14.8%), 3.9%(-8.5% to 16.3%), respectively. The results of the PPS were consistent with those of the FAS. After 8 weeks of treatment, the severity scores of individual symptoms (daytime reflux, daytime heartburn, nighttime reflux, nighttime heartburn) decreased in all groups. The differences between post-treatment and baseline in anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were -1.54±1.00, -1.91±1.00, -1.51±0.76, -1.45±0.71; -1.30±0.94, -1.59±0.96, -1.33±0.65, -1.42±0.60; and -1.74±0.85, -1.76±0.93, -1.45±0.66, -1.66±0.79, respectively. The incidence of treatment emergent adverse event of anaprazole 40 mg group, anaprazole 60 mg group and rabeprazole 20 mg group were 57.1% (28/49), 48.1% (25/52) and 60.0% (30/50), respectively, and the incidence of treatment related adverse event were 18.4% (9/24), 25.0% (13/52) and 24.0% (12/50), respectively. There were no statistically significant differences in the incidence of treatment emergent adverse event and treatment related adverse event among 3 groups (all P>0.05). Conclusion:The efficacy and safety of anaprazole 40, 60 mg/d, and rabeprazole 20 mg/d in the treatment of RE are comparable.

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion (I/R) in rats.Methods:SPF neonatal Sprague-Dawley rats of either sex, aged 1-2 days, were used, and primary cardiac fibroblasts were extracted by differential adhesion method. The cells were passaged for 2-4 generations. When the cell density reached 60%-70%, the cells were transferred and exposed to 95% N 2 + 5% CO 2 for 1 h at 4 ℃, and then exposed to 95% air + 5% CO 2 for 24-48 h at 37 ℃, and then exosomes were extracted. Twenty-four SPF healthy adult male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were divided into 3 groups ( n=8 each) according to the random number table method: control group (group C), hypothermic cardiac IR group (I/R group) and exosome + hypothermic cardiac IR group (Exo-IR group). At 48 h before equilibrium perfusion, 1.5 ml (200 μg) of exosomes secreted by cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation was injected into the tail vein in Exo-IR group, and PBS 1.5 ml was injected into the tail vein in C group and IR group each. Group C received 110 min equilibration perfusion. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and Exo-IR groups. Microelectrode arrays were applied at 20 min of equilibrium perfusion and 15 and 30 min of reperfusion to obtain myocardial conduction velocity (CV), absolute conduction inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) on the left ventricular surface of isolated rat hearts. Results:Compared with group C, the CV was significantly decreased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were increased in IR and Exo-IR groups ( P<0.05). Compared with IR group, CV was significantly increased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were decreased in Exo-IR group ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation can improve ventricular electrical conduction during hypothermic cardiac I/R in rats.

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts pretreated with sevoflurane on ventricular electrical conduction in isolated rat hearts subjected to hypothermic ischemia-reperfusion (I/R) using the multi-electrode array mapping technique.Methods:Primary cardiac fibroblasts were extracted by differential adhesion in SPF Sprague-Dawley rats of either sex.Cardiac fibroblasts of passage 2-4 were treated with 2.5% sevoflurane for 1 h, and then cultured for 24-48 h to extract exosome.SPF healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-320 g, were divided into 3 groups ( n=8 each) using a random number table method: control group (group C), I/R group and sevoflurane-pretreated cardiac fibroblast-derived exosome+ IR group (group S+ IR). Hearts were perfused for 110-min equilibration in group C. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and S+ IR groups.Exosomes 1 ml (200 μg) derived from cardiac fibroblasts pretreated with sevoflurane were injected through the tail vein at 48 h before surgery in group S+ IR, and the equal volume of normal saline was injected instead in C and IR groups.The cardiac conduction velocity (CV), conduction absolute inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) were obtained at 20 min of equilibration (T 0) and 15 and 30 min of reperfusion (T 1, 2) using the microelectrode array attaching to the left ventricular surface of the isolated heart. Results:Compared with group C, CV was significantly decreased and P 5-95 and P 5-95/P 50 were increased at T 1 ( P<0.05), and no significant change was found at T 2 in group S+ IR ( P>0.05), and CV was significantly decreased and P 5-95 and P 5-95/P 50 were increased at T 1, 2 in group IR ( P<0.05). Compared with group IR, CV was significantly increased and P 5-95 and P 5-95/P 50 were decreased at T 1, 2 in group S+ IR ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts pretreated with sevoflurane can improve ventricular electrical conduction in isolated rat hearts subjected to hypothermic I/R.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

【Objective】 To explore the effect of Genistein on the proliferation and cell cycle regulation of ovarian cancer cells. 【Methods】 Ovarian cancer OVCAR-5 cells were treated with Genistein. Cell counting and MTS assays were performed to determine the alterations of cell proliferation. Real-time PCR and Western blotting were conducted to examine the expression changes of key cell cycle regulators. 【Results】 Genistein significantly promoted the proliferation and viability of OVCAR-5 cells. After Genistein treatment, cellular mRNA and protein expression levels of cell cycle activators such as PCNA, Cyclin D1 and CDK4 were increased, but those of cell cycle inhibitors such as p21 and p27 were decreased. 【Conclusion】 Genistein can upregulate the proliferation and G1-S transition of ovarian cancer OVCAR-5 cells. The discrepancy may be caused by diverged experimental conditions and/or different ER expression patterns of cell lines. The findings may provide basic information for in-depth analysis of the role(s) and mechanisms by which genistein confers its effect on ovarian cancer cells.

Objective To develop a diagnostic model based on deep neural network for intelligent discrimination of thyroid function. Methods A total of 1616 patients ( 283 males, 1333 females, average age:52 years) who underwent thyroid imaging between May 2016 and June 2018 were selected. According to the clinical diagnosis, the 1616 cases included 299 normal thyroid cases, 876 hyperthyroidism cases and 441 hypothyroidism cases. Feature extraction and learning training were performed on 1000 training set sam-ples by two deep neural network models ( AlexNet;deep convolution generative adversarial networks ( DCGAN) ) using deep learning algorithm. Performance verifications were implemented on 616 test set samples. The con-sistency between the verification results of the two models and the clinical diagnosis was analyzed by Kappa test. Meanwhile, the time advantage of the intelligent diagnosis models was analyzed. Results The average diagnostic time of AlexNet model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 82.29％(79/96), 94.62％(369/390), 100％(130/130), respectively. The Kappa value between results of AlexNet model and clinical diagnosis was 0.886 ( P<0.05) . The average di-agnostic time of DCGAN model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 85.42％(82/96), 95.64％(373/390), 99.23％(129/130), respectively. The Kappa value between results of DCGAN model and clinical diagnosis was 0.904 ( P<0.05) . Conclusion The deep neural network intelligent diagnosis model can quickly determine the functional status of thyroid gland in thyroid imaging, and it has a high recognition accuracy, thus providing a new method for thyroid image review.