1.Associations of weekly working hours with neck and lower back work-related musculoskeletal disorders among bus drivers in Shenzhen
Yuxi WANG ; Dafeng LIN ; Shengli CHEN ; Huan GUO ; Naixing ZHANG ; Shaofan WENG
Journal of Environmental and Occupational Medicine 2025;42(3):286-292
Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of
2.Pharmacoeconomic evaluation of iruplinalkib therapy for advanced ALK-positive non-small cell lung cancer
Hong WANG ; Haonan LI ; Hui ZHANG ; Yuhang LIU ; Yeyou XU ; Kaiyuan WENG
China Pharmacy 2025;36(8):945-950
OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer (NSCLC) patients who had not previously received ALK-tyrosine kinase inhibitors (TKIs) from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial, a three-health state partitioned survival model was developed to simulate the progression of disease, with model cycle of 3 weeks and a life-year time range of 15 years; the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC, total cost, quality-adjusted life year (QALY), and incremental cost- effectiveness ratio (ICER) were compared between iruplinalkib and crizotinib; using 1-3 times China’s per capita gross domestic product (GDP) (89 358-268 074 yuan) in 2023 as the willingness-to-pay (WTP) threshold, the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis (altering the distribution of survival curves, utility values) were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen, the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY, which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan). The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However, after increasing the utility value of the disease progression state, the ICER exceeded the WTP threshold, and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system, compared with crizotinib regimen, the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.
3.Chronic Disease Management in Patients with Non-infectious Arthritis: Challenges and Solutions
Medical Journal of Peking Union Medical College Hospital 2025;16(1):1-4
Non-infectious arthritis (NIS) mainly includes osteoarthritis and inflammatory arthritis. With the aging of the population, chronic disease management of NIS patients in China will face great challenges, such as long disease duration, multi-system involvement, high demand for personalized diagnosis and treatment, lack of patient awareness, and difficulty in managing co-morbidities. To address these challenges, a systematic strategy for chronic disease management of NIS needs to be developed at the national level, which encompasses increasing popularization of science, improving the referral system, using artificial intelligence (AI) technology to assist in early diagnosis, and implementing interventions including optimized pharmacological/surgical treatments and multidisciplinary collaboration. In the future, with the deepening of the research on the application of AI technology and novel biologics, the management of chronic disease management of NIS will become more intelligent and personalized.
4.Investigation on an outbreak of acute hemorrhagic conjunctivitis at a boarding middle school in Guangdong Province
Chinese Journal of School Health 2025;46(6):878-882
Objective:
To investigate the characteristics and risk factors of an outbreak of acute hemorrhagic conjunctivitis (AHC) in a boarding middle school in Guangdong Province, in order to provide a scientific evidence for effective prevention and control of campus AHC outbreaks.
Methods:
From September 1st to 28th 2023, case identification was conducted among 559 students and 60 faculty members using standardized definition. Descriptive analysis was conducted on the three distrubution patterns of the outbreak. Questionnaires were designed, and a case-control study was adopted to analyze the possible risk factors of the disease transmission. The propensity score matching (PSM) method was used to control the difference of baseline data.
Results:
A total of 269 cases of AHC were identified, with an attack rate of 43.46%. The pathogen was confirmed as Coxsackie virus A24 variant (CA24v). Among these, 264 cases were students (attack rate of 47.23%) and 5 were staff (attack rate of 8.33%). A total of 153 pairs of PSM were successfully matched. After PSM matching, there were no statistically significant differences in gender, grade and class between the case group and the control group ( χ 2=0.12, 5.41, 11.24, P >0.05). The results of multivariate Logistic regression analysis showed that middle school students whose towels contacted with others ( OR =1.81), and direct contact with other AHC cases recently ( OR =4.89) were more likely to have AHC; while wearing glasses ( OR =0.43) and frequent use of hand sanitizer ( OR = 0.37 ) were less likely to have AHC ( P <0.05).
Conclusion
The outbreak of AHC is caused by CA24v, demonstrating rapid spread and extensive impact within the school setting.
5.Efficacy of robot-assisted versus laparoscopic parenchymal-sparing pancreatectomy in treatment of pancreatic neuroendocrine neoplasm
Guihu WENG ; Zhe CAO ; Yueze LIU ; Taiping ZHANG
Journal of Clinical Hepatology 2025;41(6):1156-1160
ObjectiveTo compare and analyze the clinical application of robot-assisted parenchymal-sparing pancreatectomy (R-PSP) and laparoscopic parenchymal-sparing pancreatectomy (L-PSP) in the treatment of pancreatic neuroendocrine neoplasm (pNEN), and to evaluate the safety and efficacy of the R-PSP procedure. MethodsA retrospective analysis was performed for the clinical data of pNEN patients who underwent parenchymal-sparing pancreatectomy in Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, from December 2017 to August 2023, and according to the minimally invasive surgical procedure, they were divided into R-PSP group and L-PSP group. R-PSP and L-PSP were compared in terms of the efficacy of minimally invasive procedure, the outcome of postoperative complications, and oncological efficacy. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; the Mann-Whitney U test was used for comparison of ranked data between two groups. ResultsA total of 45 pNEN patients were included, with 9 in the R-PSP group and 36 in the L-PSP group, and there were no significant differences in baseline data between the two groups (all P>0.05). There were no significant differences between the two groups in time of operation, intraoperative blood loss, intraoperative blood transfusion, and the rate of conversion to laparotomy (all P>0.05). Compared with the L-PSP group, the R-PSP group had a significantly longer length of postoperative hospital stay [10.00 (9.00 — 15.00) days vs 7.50 (6.00 — 10.00) days, Z=-2.356, P=0.017] and significantly higher hospital costs [86 610.44 (81 905.39 — 114 401.24) yuan vs 38 781.20 (31 708.39 — 50 514.76) yuan, Z=-4.001, P<0.001]. There were no significant differences between the two groups in the incidence rates of serious postoperative complications (Clavien-Dindo grade ≥Ⅲ), clinically relevant pancreatic fistula, delayed gastric emptying, and intra-abdominal infection (all P>0.05). The postoperative 90-day mortality rate was 0% for both groups. ConclusionR-PSP has acceptable safety and efficacy in pNEN patients in clinical practice.
6.Regulatory effects of short-chain fatty acids on oxidative stress and activation of pancreatic stellate cells
Hongna LU ; Feng XU ; Qiubo ZHANG ; Ting WENG ; Liangshun ZHANG ; Xianpeng LI
Chinese Journal of Pancreatology 2024;24(3):210-215
Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.
7.Meta-analysis on the comparison between plasma exchange and drugs in the treatment of hypertriglyceridemic pancreatitis
Chinese Journal of Pancreatology 2024;24(4):270-277
Objective:To evaluate the efficacy of plasma exchange and drugs in the treatment of hypertriglyceridemic pancreatitis (HTGP).Methods:Plasma exchange, exchange plasma,exchanges plasma, plasma or plasma exchanges, acute pancreatitis were used as keywords for research search, and the network English database such as PubMed, Embase, Cochrane Library were searched from database establishment to May 31, 2022. The prospective and retrospective cohort studies on plasma exchange and drugs in the treatment of HTGP were retrieved. The papers were screened and the quality was evaluated according to preset inclusion and exclusion criteria; and the important data were extracted. Meta-analysis was performed using RevMan5.3 software.Results:A total of 11 papers with 819 patients were included. Among them, 285 patients received plasma exchange, and 534 patients received drug treatment. The results of meta-analysis showed that plasma exchange decreased triglyceride faster than drug therapy ( OR=5.28, 95% CI 0.92-9.63, P<0.05), but plasma exchange was comparable to drug therapy on the incidence of pancreatic pseudocysts, pancreatic necrosis, acute renal failure, acute respiratory failure and shock, and mortality ( OR=0.54, 95% CI 0.23-1.29; OR=1.23, 95% CI 0.62-2.43; OR=0.85, 95% CI 0.25-2.91; OR=0.84, 95% CI 0.25-2.79; OR=0.64, 95% CI 0.31-1.34, OR=1.29, 95% CI 0.72-2.30; all P value >0.05), and patients with plasma exchange had longer hospital stays ( OR=2.09, 95% CI 0.10-4.08, P<0.05). Conclusions:Compared with drug therapy, plasma exchange can not reduce the mortality and complications of HTGP patients.
8.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
9.Comparison of open reduction hollow nail anchoring system with loop plate fixation under arthroscopy for the treat-ment of posterior cruciate ligament avulsion fractures
Rong WU ; Zhan-Feng ZHANG ; Wei WENG ; Hong-Hang YANG ; Ji-Kang MIN ; Jian-Wei SUN ; Zhe-Yuan SHEN
China Journal of Orthopaedics and Traumatology 2024;37(6):583-590
Objective To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures.Methods Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively,and divided into open reduction and internal fixation group(posterior medial approach hollow anchor system fixation)and arthroscopic fixation group(Endobutton with loop plate fixation under arthroscopy).There were 20 patients in open reduction and internal fixation group,including 16 males and 4 females,aged from 26 to 74 years old with an average of(42.9±18.8)years old;13 patients on the left side and 7 patients on the right side;12 patients were classi-fied to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were grade Ⅱ and 6 patients were grade Ⅲ in back drawer test.There were 18 patients in arthroscopic fixation group,including 11 males and 7 fe-males;aged from 24 to 70 years old with an average of(53.5±13.4)years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to type Ⅱ and 8 patiens with type Ⅲ according to Meyers-McKeever fractures classifica-tion;11 patients were grade Ⅱ and 7 patients were grade Ⅲ in back drawer test.Operation time,blood loss,and quality of im-mediate reduction were compared between two groups.Knee range of motion,knee back drawer test,and International Knee Documentation Committee(IKDC)grading,KT2000 stability evaluation and Lysholm function score of knee joint were com-pared at 6 months after operation.Results All patients were followed up for 8 to 16 months with an average of(12.3±1.9)months.There were no complications such as incision infection,fracture malunion or non-union,and internal fixation loosening occurred.The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation.Operation time and blood loss in open reduction and internal fixation group were(56.4±7.1)min and(63.2±10.2)ml,while(89.9±7.4)min and(27.7±8.7)ml in arthroscopic fixation group,respectively,and had significant difference between two groups(P<0.05).There were no differences in immediate reduction quality(x2=0.257,P=0.612),knee joint range of motion at 6 months after opertaion(t=0.492,P=0.626),knee joint rear drawer test(x2=0.320,P=0.572),IKDC classification of knee joint(x2=0.127,P=0.938),KT2000stability evaluation(x2=0.070,P=0.791),and knee Lysholmfunction score(t=0.092,P=0.282)between two groups.Conclusion Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixa-tion for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results,and arthroscopic surgery has less bleeding,but also has a longer learning curve and longer operation time than traditional inci-sion surgery.The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.
10.Changing distribution and resistance profiles of common pathogens isolated from urine in the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Yanming LI ; Mingxiang ZOU ; Wen'en LIU ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2024;24(3):287-299
Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8%(62 219/261 893),and gram-negative bacteria 76.2%(199 674/261 893).The most common species were E.coli(46.7%),E.faecium(10.4%),K.pneumoniae(9.8%),E.faecalis(8.7%),P.mirabilis(3.5%),P.aeruginosa(3.4%),SS.agalactiae(2.6%),and E.cloacae(2.1%).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2%,52.8%and 37.0%,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7%,18.5%,16.4%,and 40.3%,respectively.Lower than 10%of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90%of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was<2%.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.


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