Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2020, and analyzed the data collected from the national schistosomiasis prevention and control system and national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan, Hubei, Anhui, Jiangxi and Hunan provinces maintained the criteria of transmission control by the end of 2020. A total of 450 counties (cites, districts) were found to be endemic for schistosomiasis in China, with 28 376 endemic villages covering 71 370 400 people at risk of infections. Among the 450 endemic counties (cities, districts), 74.89% (337/450), 21.87% (98/450) and 3.33% (15/450) achieved the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2020, 29 517 cases with advanced schistosomiasis were documented in China. In 2020, 11 117 655 individuals received inquiry examinations and 1 798 580 were positive; 5 263 082 individuals received serological tests and 83 179 were sero-positive. A total of 273 712 individuals received stool examinations and 3 were positive, including one case of acute schistosomiasis. In 2020, snail survey was performed in 19 733 endemic villages in China and Oncomelania snails were found in 7 309 villages, accounting for 37.04% of all surveyed villages, with 15 villages identified with emerging snail habitats. Snail survey covered an area of 736 984.13 hm² and 206 125.22 hm² snail habitats were found, including 1 174.67 hm² emerging snail habitats and 1.96 hm² habitats with infected snails. In 2020, 544 424 bovines were raised in the schistosomiasis-endemic areas of China, and 147 887 received serological examinations, with 326 positives detected, while 130 673 bovines received stool examinations, with no positives identified. In 2020, there were 19 214 patients with schistosomiasis receiving praziquantel chemotherapy, and 964 103 person-time individuals and 266 280 herd-time bovines were given expanded chemotherapy. In 2020, molluscicide treatment was performed in 136 141.92 hm² snail habitats, and the actual area of chemical treatment was 71 980.22 hm², while environmental improvements were performed in snail habitats covering an area of 1 464.03 hm². Data from the national schistosomiasis surveillance sites of China showed that the mean prevalence of Schistosoma japonicum infections were both zero in humans and bovines in 2020, and no S. japonicum infection was detected in snails. The results demonstrate that the overall endemic status of schistosomiasis remains at a low level in China and the goal of the National Thirteenth Five-Year Plan for Schistosomiasis Control was achieved as scheduled; however, the endemic situation of schistosomiasis rebounded in local areas. Precision schistosomiasis control and intensified monitoring of the endemic situation and transmission risk of schistosomiasis are required to be performed to facilitate the progress towards elimination of schistosomiasis steadily.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Acute-On-Chronic Liver Failure ; Humans ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

Objective: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. Methods: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. Results: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively. Conclusion GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2019, and analyzed the data collected from the national schistosomiasis prevention and control system and 455 national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, Shanghai, Zhejiang, Fujian, Guangdong and Guangxi continued to consolidate the achievements of schistosomiasis elimination, Sichuan Province achieved transmission interruption, Jiangsu newly achieved the standard of transmission interruption and 5 provinces of Yunnan, Hubei, Anhui, Jiangxi and Hunan maintained transmission control by the end of 2019. There were 450 endemic counties (cities, districts) endemic for schistosomiasis, including 28 500 endemic villages covering 70 667 800 people at risk of infections. Among the 450 endemic counties (citis, districts), 66.89% (301/450), 28.44% (128/450) and 4.67% (21/450) kept the criteria of elimination, transmission interruption and transmission control of schistosomiasis, respectively. By the end of 2019, a total of 30 170 advanced schistosomiasis cases were documented in China. In 2019, a total of 12 090 712 individuals received inquiry examinations and 1 740 764 were positive; 5 158 369 individuals received serological tests and 89 753 were seropositive. A total of 327 475 individuals received stool examinations and 5 were positive, including one case of acute schistosomiasis. In 2019, snail survey was performed in 19 726 endemic villages in China and Oncomelania snails were found in 7 322 villages, accounting for 37.12% of all surveyed villages, with 6 villages with emerging snail habitats. Snail survey covered an area of 585 286.24 hm² and 174 270.42 hm² snail habitats were found, including emerging snail habitats of 64.20 hm²; however, no infected snails were identified. In 2019, a total of 605 965 bovines were raised in the schistosomiasis endemic areas of China, and 183 313 received serological examinations, with 1 176 positives detected, while 134 978 bovines received stool examinations, with 7 positives identified. In 2019, there were 28 557 patients with schistosomiasis receiving praziquantel chemotherapy, and expanded chemotherapy was given to 1 008 083 person-times; there were 7 bovines with schistosomiasis receiving praziquantel chemotherapy, and 296 053 herd-times expanded chemotherapy was given to bovines. In 2019, snail habitats at an area of 128 754.26 hm² were given chemical treatment, and the actual area of chemical treatment was 69 605.55 hm², while environmental improvements were performed in snail habitats covering an area of 2 847.00 hm². Data from the 455 national schistosomiasis surveillance sites of China showed that the mean Schistosoma japonicum infection rates were both zero in humans and bovines in 2019, and no infected snails were found. The results demonstrate that the overall endemic situation of schistosomiasis remains at a lower infection level in China; however, there is still a risk of schistosomiasis transmission. To achieve the target set in the National Thirteenth Five-Year Plan for Schistosomiasis Control and consolidate the achievements of schistosomiasis control, precision control on schistosomiasis still needs to be reinforced in China.

This report presented the endemic status of schistosomiasis in the People’s Republic of China at a national level in 2018, and analyzed the data collected from the national schistosomiasis prevention and control system and 453 national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) endemic for schistosomiasis in China, 5 provinces (municipality and autonomous region), including Shanghai, Zhejiang, Fujian, Guangdong and Guangxi, continued to consolidate the achievements of schistosomiasis elimination, Sichuan Province achieved transmission interruption and 6 provinces of Yunnan, Jiangsu, Hubei, Anhui, Jiangxi and Hunan achieved transmission control by the end of 2018. There were 450 endemic counties (cities, districts) covering 260 million people, specifically including 28 456 endemic villages covering 70.059 7 million people at risk of infection. Among the 450 endemic counties (cities, districts), 58.44% (263/450), 27.56% (124/450) and 14.00% (63/450) reached the criteria of elimination, transmission interruption and transmission control, respectively. By the end of 2018, a total of 29 214 advanced schistosomiasis cases were documented in China. In 2018, a total of 11.127 6 million individuals received inquiry examinations and 2.062 9 million were positive; 7.191 4 million individuals received serological tests and 138.5 thousand of them were positive, 532.2 thousand individuals received stool examinations and 8 were positive in China. In 2018, snail survey was performed in 19 821 endemic villages and Oncomehania snails were found in 7 321 villages, accounting for 36.94% of all surveyed villages, with 3 newly detected villages with snails in China. Snail survey covered an area of 590 241.01 hm² and 168 319.41 hm² snail habitats were found, including emerging snail habitats of 61.28 hm²; however, no infected snails were identified. In 2018, a total of 646 823 bovines were raised in the schistosomiasis endemic areas of China, and 225 258 received serological examinations, with 2 638 positives detected, while 164 803 bovines received stool examinations, with 2 positives identified. In 2018, there were 90 388 patients with schistosomiasis receiving praziquantel chemotherapy, and expanded chemotherapy was given to 1 490 594 person-times; there were two bovines with schistosomiasis receiving praziquantel chemotherapy, and expanded chemotherapy was given to 352 577 bovine-times; chemical treatment was conducted in an area of 141 660.87 hm², including an actual mollusciciding area of 75 308.26 hm², and environmental improvements were performed in an area of 4 738.37 hm² in China. Data from the 453 national schistosomiasis surveillance sites of China showed that the mean Schistosoma japonicum infection rates were 0.001 5% and zero in humans and bovines in 2018, respectively, and no infected snails were found. The results demonstrate that the endemic situation of schistosomiasis appears a tendency towards a continuous decline in China; however, there is still a risk of schistosomiasis transmission, and challenges remain in achieving the target set in the Thirteenth Five-Year National Plan for Schistosomiasis Control in 2020 in some regions.

This report presents the endemic status of schistosomiasis in the People’s Republic of China at national level in 2017, and analyzes the data collected from the national schistosomiasis prevention and control system and 457 national schistosomiasis surveillance sites. Among the 12 provinces (municipality and autonomous region) being endemic of schistosomiasis japonica in P. R. China, 5 provinces (municipality and autonomous region), i.e., Shanghai, Zhejiang, Fujian, Guangdong and Guangxi, continued to consolidate the status of elimination of schistosomiasis. Sichuan Province achieved the transmission interruption and 6 provinces of Yunnan, Jiangsu, Hubei, Anhui, Jiangxi and Hunan kept the transmission control by the end of 2017. There were 450 endemic counties (cities, districts) covering 259 million people, specifically including 28 544 endemic villages of 70 324.5 thousand people at risk. Among the 450 endemic counties (cities, districts), 47.78% (215/450), 34.00% (153/450) and 18.22% (82/450) reached the criteria of elimination, transmission interruption and transmission control, respectively. By the end of 2017, a total of 8 401 113 individuals received schistosomiasis examinations and 14 individuals were parasitologically diagnosed, decreased by 97.67% compared with 600 cases in 2016. It was estimated of 37 601 cases of schistosome infection, decreased by 30.95% compared with 54 454 cases in 2016. One acute schistosomiasis case was reported in 2017. There were 29 407 advanced schistosomiasis cases documented in 2017. Oncomelania hupensis snail surveys were performed in 19 784 endemic villages and O. hupensis snails were found in 7 310 villages, accounting for 36.95% of total villages, with 19 newly detected villages with snails.The snail survey covered an area of 622454.49 hm² and snails were found in an area of 172501.56 hm², including a newly detected area of 208.54 hm². No schistosome-infected snails were found in 2017. A total of 737 016 bovines were raised in the schistosomiasis endemic areas. Of them, 454 830 bovines received the examinations for schistosome infection, and 1 bovine was stool examination positive. There were 119 326 schistosomiasis cases receiving chemotherapy in 2017, with 1 973 968 individuals undergoing expanded chemotherapy; one bovine with schistosomiasis receiving chemotherapy, with 418 925 bovines undergoing expanded chemotherapy. A total of 144 605.31 hm² area with snail was controlled by using molluscicides, with actual molluscicide-treated area of 73 755.37 hm²; and 5 002.92 hm² area with snail was treated by environmental modification. Based on the data from the 457 national schistosomiasis surveillance sites, the mean Schistosoma japonicum infection rate was 0.001 6% and 0 in humans and bovines, respectively. No schistosome-infected snails were found by microscopic examinations in all the surveillance sites, and 7 snail samples with schistosome nucleic acid positive were detected by loopmediated isothermal amplification (LAMP) among 6 surveillance sites. The results demonstrate a continuous decline trend on the endemic situation of schistosomiasis in P. R. China. However, the risk of epidemic rebound still exists in some regions and it is still a challenge to achieve the target set by the Thirteenth Five-Year National Plan for Schistosomiasis Control in 2020.