Objective To analyze the urban drinking water quality and its influencing factors in Anhui Province from 2014 to 2022, and to provide a scientific basis for water quality improvement and protection. Methods The data were collected, saved and monitored according to the Standard Test Method for Drinking Water (GB/T5750-2006) and evaluated according to the Hygienic Standard for Drinking Water (GB 5749-2006). Results A total of 20 941 samples were collected, and the overall qualified rate was 84.26%. The qualified rate of urban drinking water increased from 76.9% in 2014 to 93.3% in 2022, and the qualified rate of water quality was on the rise (χ²=544.43, P＜0.01). From 2014 to 2022, the qualified rate of water quality in dry season was higher than that in wet season (χ²=35.98, P<0.001), the qualified rate of surface water was higher than that of ground water (χ²=4440.8, P<0.001), and the qualified rate of peripheral tap water was higher than that of factory water (χ²=145.1, P<0.001). Among all kinds of disinfection methods, chlorination disinfection had the highest qualified rate (χ²=1483.8, P<0.001). The qualified rate of water quality increased with the increase of the scale of water plant. Among the inspected indicators, the main unqualified indicators were chlorine dioxide (7.72%), fluoride (7.41%), free residual chlorine (3.90%), and total bacterial count (2.13%). Conclusion The passing rate of urban drinking water quality in Anhui Province is on an upward trend, and the quality of urban drinking water has improved. However, it is still important to pay attention to the problem of excessive microorganism and fluoride in water, and the quality of drinking water varies from place to place.

OBJECTIVE To summarize the current status of position training for clinical pharmacists in China and provide references for the continuous optimization of such training programs. METHODS SinoMed， CNKI，VIP and Wanfang Data were electronically searched to collect position training of clinical pharmacists studies from the inception until November 5th 2024. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS & A total of 68 pieces of relevant literature were included in the study. Among them， 50 studies reported on training content， 49 involved the allocation of teaching resources in the bases， 48 addressed training methods， and 39 focused on training evaluation； only 2 studies mentioned faculty development. There were notable variations in the clinical pharmacist training programs across different bases， particularly in the allocation of teaching resources， such as the composition of the teaching team and the utilization of auxiliary teaching tools. Additionally， differences existed in training approaches， such as those employing a single method versus a blended approach. Conversely， the core training content of each base generally revolved around clinical pharmacy practice， demonstrating a degree of consistency. Moreover， the overall emphasis on teacher training and assessment tended to be obviously insufficient. Each base can focus on enhancing the competence of clinical pharmacists by allocating teaching resources， selecting training methods， improving training content， and using evaluation tools， to further enhance the quality of clinical pharmacist training.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.
Fermentation ; Aspergillus nidulans/genetics* ; Echinocandins/genetics* ; Bioreactors/microbiology* ; Fungal Proteins/biosynthesis* ; Metabolic Engineering

Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education* ; Teaching ; China ; Humans

Objective:To evaluate the 1-year postoperative efficacy and nutritional indicators of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in obese patients.Methods:This retrospective observational study included patients with a body mass index (BMI) of ≥40.0 kg/m 2 regardless of other related metabolic diseases and patients with severe type 2 diabetes and a BMI between 27.5 and 40.0 kg/m 2. The clinical data of 66 obese patients who underwent SADI-S at the Bariatric and Metabolic Surgery Department of China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were collected, including 53 cases of da Vinci robotic surgery and 13 cases of laparoscopic surgery. The patients comprised 38 men and 28 women with a median age of 35 (18–61) years and a mean preoperative BMI of 42.93 ± 6.82 kg/m 2. A total of 38 patients had type 2 diabetes, and 46 had hyperuricemia, 45 had hypertension, 35 had hyperlipidemia, 12 had hypercholesterolemia, and 12 had a high low-density lipoprotein (LDL) level. The main observation indicators were (1) intraoperative and postoperative conditions; (2) weight loss outcomes, including body weight, BMI, excess body weight loss (%EWL), and total body weight loss (%TWL) at 3, 6, and 12 months after surgery; (3) effects of treatment on metabolic disease; and (4) changes in nutrient indicators. Results:(1) Intraoperative and postoperative conditions: All patients successfully underwent SADI-S with neither conversion to laparotomy nor death. Four (6.1%) patients developed postoperative complications, and all of them recovered and were discharged after conservative or surgical treatment. (2) Weight loss outcomes: %EWL at 3, 6, and 12 months after surgery was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65, respectively, and %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89, respectively. Body weight and BMI 3 to 12 months after surgery were significantly lower than those before surgery (all P < 0.001). (3) Effect of treatment on metabolic disease: 3 to 12 months after surgery, fasting blood sugar, HbA1c, uric acid, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, LDL, and other indicators were significantly lower than those before surgery (all P < 0.05). Twelve months after surgery, the remission rates of diabetes, hyperuricemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and high LDL were 100% (38/38), 65.2% (30/46), 62.2% (28/45), 94.3% (33/35), 100% (12/12), and 100% (12/12), respectively. (4) Changes in nutrient indicators: Compared with the preoperative nutrient levels, the hemoglobin and hematocrit levels were lower at 3 to 12 months after surgery, the total protein level was lower at 6 to 12 months after surgery, the albumin level was lower at 6 months after surgery, and the ferritin level was lower at 3 months after surgery. The differences were statistically significant (all P < 0.05). The incidence of anemia was 6.1% (4/66), hypoalbuminemia was 4.5% (3/66), and ferritin deficiency was 4.5% (3/66), all of which were improved or normalized through conservative treatment. Twelve months after surgery, 30 (45.5%) patients had vitamin A deficiency, 17 (25.8%) had vitamin E deficiency, 11 (16.7%) had folic acid deficiency, 2 had potassium deficiency (3.0%), 3 (4.5%) had calcium deficiency, 2 (3.0%) had magnesium deficiency, 9 (13.6%) had iron deficiency, and 16 (24.2%) had zinc deficiency. However, no relevant clinical symptoms occurred. Conclusions:SADI-S has a very significant effect on weight loss and alleviation of metabolic diseases. Nutrient deficiencies after SADI-S mainly involve vitamin A, vitamin E, zinc, and folic acid. The long-term efficacy and safety of SADI-S still need further follow-up observation.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To evaluate the 1-year postoperative efficacy and nutritional indicators of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in obese patients.Methods:This retrospective observational study included patients with a body mass index (BMI) of ≥40.0 kg/m 2 regardless of other related metabolic diseases and patients with severe type 2 diabetes and a BMI between 27.5 and 40.0 kg/m 2. The clinical data of 66 obese patients who underwent SADI-S at the Bariatric and Metabolic Surgery Department of China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were collected, including 53 cases of da Vinci robotic surgery and 13 cases of laparoscopic surgery. The patients comprised 38 men and 28 women with a median age of 35 (18–61) years and a mean preoperative BMI of 42.93 ± 6.82 kg/m 2. A total of 38 patients had type 2 diabetes, and 46 had hyperuricemia, 45 had hypertension, 35 had hyperlipidemia, 12 had hypercholesterolemia, and 12 had a high low-density lipoprotein (LDL) level. The main observation indicators were (1) intraoperative and postoperative conditions; (2) weight loss outcomes, including body weight, BMI, excess body weight loss (%EWL), and total body weight loss (%TWL) at 3, 6, and 12 months after surgery; (3) effects of treatment on metabolic disease; and (4) changes in nutrient indicators. Results:(1) Intraoperative and postoperative conditions: All patients successfully underwent SADI-S with neither conversion to laparotomy nor death. Four (6.1%) patients developed postoperative complications, and all of them recovered and were discharged after conservative or surgical treatment. (2) Weight loss outcomes: %EWL at 3, 6, and 12 months after surgery was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65, respectively, and %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89, respectively. Body weight and BMI 3 to 12 months after surgery were significantly lower than those before surgery (all P < 0.001). (3) Effect of treatment on metabolic disease: 3 to 12 months after surgery, fasting blood sugar, HbA1c, uric acid, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, LDL, and other indicators were significantly lower than those before surgery (all P < 0.05). Twelve months after surgery, the remission rates of diabetes, hyperuricemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and high LDL were 100% (38/38), 65.2% (30/46), 62.2% (28/45), 94.3% (33/35), 100% (12/12), and 100% (12/12), respectively. (4) Changes in nutrient indicators: Compared with the preoperative nutrient levels, the hemoglobin and hematocrit levels were lower at 3 to 12 months after surgery, the total protein level was lower at 6 to 12 months after surgery, the albumin level was lower at 6 months after surgery, and the ferritin level was lower at 3 months after surgery. The differences were statistically significant (all P < 0.05). The incidence of anemia was 6.1% (4/66), hypoalbuminemia was 4.5% (3/66), and ferritin deficiency was 4.5% (3/66), all of which were improved or normalized through conservative treatment. Twelve months after surgery, 30 (45.5%) patients had vitamin A deficiency, 17 (25.8%) had vitamin E deficiency, 11 (16.7%) had folic acid deficiency, 2 had potassium deficiency (3.0%), 3 (4.5%) had calcium deficiency, 2 (3.0%) had magnesium deficiency, 9 (13.6%) had iron deficiency, and 16 (24.2%) had zinc deficiency. However, no relevant clinical symptoms occurred. Conclusions:SADI-S has a very significant effect on weight loss and alleviation of metabolic diseases. Nutrient deficiencies after SADI-S mainly involve vitamin A, vitamin E, zinc, and folic acid. The long-term efficacy and safety of SADI-S still need further follow-up observation.

Objective:To explore the mechanism of exacerbating chronic graft versus host disease (GVHD) in mice with inflammatory status and enhancing immune injury in mice with PD-1.Method:Bone marrow and spleen cells of DBA/2 mice were injected into BALB/C mice pretreated with chemotherapy regimen (Flu+Bu) for constructing a chronic GVHD model. The animals were assigned into two groups of zymosan (100M SPL+10M BM+Zymosan) and control (100M SPL+10M BM+ PBS). After transplantation, two groups of mice were observed for weight changes, survival status and chronic GVHD manifestations. Target organ tissues were harvested for pathological scoring. Flow cytometry was employed for detecting cell subpopulations and surface co-stimulatory molecules in target organs. PD-1 monoclonal antibody was injected into inflammatory murine model. Mice were observed and target organ cells were harvested for subsets and co-stimulatory factors.Result:In in vivo experiments, zymosan group showed more significant changes of chronic GVHD with higher mortality rate, faster weight loss and more severe symptoms of GVHD. At Week 2 post-transplantation, hematoxylin-eosin stain of target organ tissue was performed for pathology examination. Zymosan group showed more lymphocyte infiltration, more severe inflammation and more significant tissue injury with higher GVHD pathological score. The proportion of M2 in liver/lung of zymosan group was significantly lower than that of control group ( P<0.05) and no significant difference existed in the proportion of M1. In in vivo experiments, M1 ratio of splenic cell spiked markedly in zymosan group as compared to control group while M2 ratio declined greatly. The secretions of IL-4 and IL-10 dropped significantly while co-stimulatory molecules CD80 and CD86 rose obviously. Conclusion:The worsening graft-versus-host disease in inflammatory mice with anti-PD1 treatment is associated with a decline of Treg proportion.

Objective:To study the dosimetric differences of hippocampal-avoidance whole brain radiotherapy(HA-WBRT)between non-uniform 9-fields intensity-modulated radiotherapy-flatten filter(9F-IMRT-FF)and 9-fields intensity-modulated radiotherapy-flatten filter-free(9F-IMRT-FFF)mode.Methods:From January to December 2023,the simulated images of computed tomography(CT)location of 20 patients with intracranial metastases who had completed whole-brain radiotherapy at the Department of Radiotherapy of Chengde Central Hospital were selected.The radiotherapy plans of two kinds of modes of brand-new 9F-IMRT-FF and 9F-IMRT-FFF were redesigned in the planning system.The differences of dosimetric parameters of the two kinds of mode plans were compared,as well as the differences of irradiation efficiency of accelerator.Results:The exposure dose(D2%)of 2%volume of target region of planned target volume(PTV)of 9F-IMRT-FFF mode was significantly lower than that of 9F-IMRT-FF mode(t=-2.496,P<0.05).The exposure dose(D100%)of 100%volume of target region,the maximum dose(Dmax)and the mean dose(Dmean)of the left side of hippocampus of 9F-IMRT-FFF mode plan were significantly lower than those of 9F-IMRT-FF mode plan,with statistically significant(Z=-3.179,-3.018,-2.145,P<0.05),respectively.The D100%and Dmax of the right side of hippocampus of 9F-IMRT-FFF mode plan were significantly lower than those of 9F-IMRT-FF mode plan,with statistically significant(Z=-3.099,-3.260,P<0.05),respectively.The monitor unit(MU)value of 9F-IMRT-FFF mode plan increased by 25%than that of 9F-IMRT-FF mode plan,while the treatment time of 9F-IMRT-FFF mode plan shortened 38%than that of 9F-IMRT-FF mode plan,with statistically significant(t=-9.664,-13.312,P<0.05),respectively.Conclusion:Both the non-uniform 9F-IMRT-FF and the 9F-IMRT-FFF can meet the clinically requirement.The 9F-IMRT-FFF has better modulation capabilities in beams,which has more advantages in reducing the dose of radiotherapy for hippocampus,and reducing treatment time,and increasing treatment efficiency.