1.Study on the antibacterial property of EGCG/PLL phenolamine coating integrated chlorhexidine on porous titanium surface
Huilei Hong ; Jianguang Xu ; Hua Qiu
Acta Universitatis Medicinalis Anhui 2025;60(1):109-116
Objective:
To construct a phenolamine cross-linked coating composed of epigallocatechin gallate(EGCG) and poly-L-lysine(PLL) on the surface of the porous pure Ti integrated with the antibacterial substance chlorhexidine(CHX), and to study the antibacterial property and biosafety.
Methods:
A porous structure(pTi group) was formed on the surface of titanium samples by alkaline heat treatment. Then the pTi group was immersed in the mixed solution of EGCG and PLL in an alkaline aerobic environment for 24 h to obtain the phenolamine group samples(EP group). Finally, the titanium tablets were further immersed in the aqueous solution of chlorhexidine(CHX) for 24 h to obtain the antibacterial groups(EPC group). Microstructure and properties of the surface were characterized by scanning electron microscopy(SEM), X-ray photoelectron spectrometer(XPS) and water contact angle measuring instrument. The antibacterial properties of coating were observed and evaluated by nephelometry, inhibition zone method and live/dead bacterial staining. The cytocompatibility of the coating was evaluated by MTT method and cell fluorescence staining, and the cell adhesion and proliferation ability in bacterial environment were evaluated by the co-culture of bacteria and cells.
Results:
SEM results showed that the pore size of samples after alkali heat treatment decreased with the deposition of the phenolamine coating. The measurement of water contact angle showed that the contact angle increased significantly with the grafting of coating. The intensity of N1s and C1s peaks increased and Ti2p and O1s peaks decreased detected by XPS tests. The Cl2p peak appeared in EPC group referred to the control group. The antibacterial experimentsin vitroshowed that the antibacterial samples could perform effective antibacterial effects on Staphylococcus aureus and Aggregatibacter actinomycetem-comitans for at least 7 days. In the biocompatibility experiments, MTT and cell fluorescence staining results showed that the adherent cells had good morphology and proliferative activity. The bacteria-cell co-culture results showed that the EPC groups could provide a good environment for cell proliferation and growth with excellent antibacterial properties.
Conclusion
Chlorhexidine-grafted phenolamine deposited on porous titanium surface displays an effective antibacterial effect with good biosafety performance, which can play an antibacterial role in the bacterial environment while ensuring cell adhesion and proliferation.
2.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
3.Endoscopic submucosal dissection of gastrointestinal polyps with a novel plasma radio frequency generator and a disposable mucosal incision knife: A prospective, multicenter, non-inferiority, randomized, controlled clinical trial
Baohui SONG ; Guijun SHI ; Xiaoyue XU ; Jiaxin XU ; Li FENG ; Jianguang XU ; Pinghong ZHOU ; Mingyan CAI
Chinese Journal of Gastrointestinal Surgery 2025;28(4):384-391
Objective:To evaluate the efficacy and safety of a new plasma radiofrequency generator and a disposable mucosal incision knife for endoscopic submucosal dissection (ESD) of gastrointestinal lesions.Methods:This study is a prospective, randomized, non-inferiority multicenter study (Chinese Clinical Trial Registry No.: ChiCTR2000041394). The inclusion criteria for cases are as follows: (1) being able to understand and voluntarily participate in this clinical trial, and voluntarily signing the informed consent form; (2) being 18-70 years old, regardless of gender; (3) having a gastrointestinal lesion and meeting the endoscopic treatment conditions for the indications of endoscopic submucosal dissection (ESD). The exclusion criteria are: (1) meeting the contraindications for ESD; (2) having a surgical contraindication due to coagulation dysfunction or still taking anticoagulants 1 week before surgery; (3) having coagulation dysfunction, that is, the prothrombin time is prolonged by more than 3 seconds (more than 5 seconds in patients with liver disease), or the activated partial thromboplastin time is prolonged by more than 10 seconds, and the platelet count is < 70×10?/L; (4) having severe cardiopulmonary insufficiency and being unable to tolerate the surgery; (5) being a reproductive-aged woman with a positive blood or urine pregnancy test or a lactating woman; (6) the investigator deems that there are other factors that are not suitable for inclusion or affect the subject's participation. Patients who underwent ESD treatment for gastrointestinal lesions from March 2019 to April 2023 at the Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University, the Department of Gastroenterology of Minhang District Central Hospital in Shanghai, and the Department of Gastroenterology of Quzhou People's Hospital were prospectively included. The experimental group used a new plasma radiofrequency therapy instrument and a disposable mucosal incision knife, while the control group used a high-frequency electrosurgical system and a disposable mucosal incision knife. The primary efficacy indicator was the en bloc resection success rate, the secondary efficacy indicators included the coagulation success rate, and the operation stability of the plasma radiofrequency therapy instrument and the disposable mucosal incision knife; the safety indicators included the incidence of intraoperative bleeding, intraoperative perforation, and postoperative complications. Results:The study cohort comprised 194 patients, 95 in the experimental group and 99 in the control group. Analysis of the full set showed rates of en bloc resection of 97.89% (93/95) and 96.97% (96/99) in the experimental and control groups, respectively; the difference being 0.53% (-5.58%, 6.64%). Analysis of the compliance set showed rates of en bloc resection of 97.83% (90/92) and 96.88% (93/96) in the experimental and control groups, respectively; the difference being 0.58% (-5.79%, 6.94%). These data indicate that the rate of en bloc resection in the experimental group using plasma radiofrequency therapy and disposable mucosal incision was not inferior to that of the control group. The rates of achieving intraoperative coagulation in the experimental and control groups were 7.14% (5/70) and 5.97% (4/67), respectively; this difference is not statistically significant ( P=1.000). The control group had a significantly better rate of using the same instruments throughout the procedure than did the experimental group ( P<0.001). In the safety analysis set, the incidences of intraoperative and postoperative adverse events did not differ significantly between the two groups (both P>0.05). Conclusion:Plasma radiofrequency therapy equipment and a disposable mucosal incision knife are safe and effective instruments for performing ESD of gastrointestinal lesions.
4.Analysis of teachers' willingness and influencing factors regarding the adoption of flipped classroom teaching mode in undergraduate pediatrics education
Wenrui XU ; Jianguang QI ; Ying LIAO ; Penghui WU ; Tian SANG ; Jie LIU ; Juan ZHANG ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):460-465
Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease(Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%( n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%( n=60) considered its effectiveness comparable, and 20.59%( n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%( n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom( P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.
5.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
6.Endoscopic submucosal dissection of gastrointestinal polyps with a novel plasma radio frequency generator and a disposable mucosal incision knife: A prospective, multicenter, non-inferiority, randomized, controlled clinical trial
Baohui SONG ; Guijun SHI ; Xiaoyue XU ; Jiaxin XU ; Li FENG ; Jianguang XU ; Pinghong ZHOU ; Mingyan CAI
Chinese Journal of Gastrointestinal Surgery 2025;28(4):384-391
Objective:To evaluate the efficacy and safety of a new plasma radiofrequency generator and a disposable mucosal incision knife for endoscopic submucosal dissection (ESD) of gastrointestinal lesions.Methods:This study is a prospective, randomized, non-inferiority multicenter study (Chinese Clinical Trial Registry No.: ChiCTR2000041394). The inclusion criteria for cases are as follows: (1) being able to understand and voluntarily participate in this clinical trial, and voluntarily signing the informed consent form; (2) being 18-70 years old, regardless of gender; (3) having a gastrointestinal lesion and meeting the endoscopic treatment conditions for the indications of endoscopic submucosal dissection (ESD). The exclusion criteria are: (1) meeting the contraindications for ESD; (2) having a surgical contraindication due to coagulation dysfunction or still taking anticoagulants 1 week before surgery; (3) having coagulation dysfunction, that is, the prothrombin time is prolonged by more than 3 seconds (more than 5 seconds in patients with liver disease), or the activated partial thromboplastin time is prolonged by more than 10 seconds, and the platelet count is < 70×10?/L; (4) having severe cardiopulmonary insufficiency and being unable to tolerate the surgery; (5) being a reproductive-aged woman with a positive blood or urine pregnancy test or a lactating woman; (6) the investigator deems that there are other factors that are not suitable for inclusion or affect the subject's participation. Patients who underwent ESD treatment for gastrointestinal lesions from March 2019 to April 2023 at the Endoscopy Center of Zhongshan Hospital Affiliated to Fudan University, the Department of Gastroenterology of Minhang District Central Hospital in Shanghai, and the Department of Gastroenterology of Quzhou People's Hospital were prospectively included. The experimental group used a new plasma radiofrequency therapy instrument and a disposable mucosal incision knife, while the control group used a high-frequency electrosurgical system and a disposable mucosal incision knife. The primary efficacy indicator was the en bloc resection success rate, the secondary efficacy indicators included the coagulation success rate, and the operation stability of the plasma radiofrequency therapy instrument and the disposable mucosal incision knife; the safety indicators included the incidence of intraoperative bleeding, intraoperative perforation, and postoperative complications. Results:The study cohort comprised 194 patients, 95 in the experimental group and 99 in the control group. Analysis of the full set showed rates of en bloc resection of 97.89% (93/95) and 96.97% (96/99) in the experimental and control groups, respectively; the difference being 0.53% (-5.58%, 6.64%). Analysis of the compliance set showed rates of en bloc resection of 97.83% (90/92) and 96.88% (93/96) in the experimental and control groups, respectively; the difference being 0.58% (-5.79%, 6.94%). These data indicate that the rate of en bloc resection in the experimental group using plasma radiofrequency therapy and disposable mucosal incision was not inferior to that of the control group. The rates of achieving intraoperative coagulation in the experimental and control groups were 7.14% (5/70) and 5.97% (4/67), respectively; this difference is not statistically significant ( P=1.000). The control group had a significantly better rate of using the same instruments throughout the procedure than did the experimental group ( P<0.001). In the safety analysis set, the incidences of intraoperative and postoperative adverse events did not differ significantly between the two groups (both P>0.05). Conclusion:Plasma radiofrequency therapy equipment and a disposable mucosal incision knife are safe and effective instruments for performing ESD of gastrointestinal lesions.
7.Analysis of teachers' willingness and influencing factors regarding the adoption of flipped classroom teaching mode in undergraduate pediatrics education
Wenrui XU ; Jianguang QI ; Ying LIAO ; Penghui WU ; Tian SANG ; Jie LIU ; Juan ZHANG ; Yuwu JIANG
Chinese Journal of Medical Education Research 2025;24(4):460-465
Objective:To investigate teachers' evaluation and willingness and the influencing factors regarding the adoption of the flipped classroom teaching mode in undergraduate pediatrics education.Methods:From December 2022 to December 2024, a questionnaire survey was conducted among the teachers who were responsible for teaching Child Health and Disease(Pediatrics) to the eight-year clinical medicine students at Peking University Health Science Center. Their views, evaluation, and willingness of implementing the flipped classroom teaching mode were investigated. Logistic regression analysis was performed using SPSS 26.0 software to explore the factors influencing teachers' willingness to adopt the flipped classroom teaching mode.Results:A total of 102 questionnaires were collected. Among the teachers, 20.59%( n=21) believed that the teaching effect of the flipped classroom was better than that of the traditional class, 58.82%( n=60) considered its effectiveness comparable, and 20.59%( n=21) found it less effective. The most influential factors affecting the effectiveness of flipped classroom were students' self-learning with online videos [(4.39±0.73) points], student participation in the flipped classrooms [(4.26±0.72) points], the adequacy of teachers' pre-class preparation [(4.18±0.65) points], and the suitability of the teaching content for the flipped classroom [(4.11±0.76) points]. Teachers believed that the flipped classroom significantly enhanced students' autonomous learning ability [(4.11±0.63) points], clinical thinking [(4.04±0.58) points], and expression skills [(3.80±0.61) points]. Additionally, 78.43%( n=80) of the teachers expressed willingness to continue participating in flipped classroom teaching. Factors influencing teachers' willingness to adopt the flipped classroom included gender, satisfaction with students' classroom participation, and personal experience with the effectiveness of the flipped classroom( P<0.05). Conclusions:The flipped classroom teaching mode is well-accepted by teachers. Students' classroom participation affects teachers' willingness to continue using the flipped classroom teaching mode. In the future, the content of flipped classroom should be arranged individually according to specific teaching objectives to increase students' classroom participation and promote the cultivation of students' ability.
8.Study on the differences in clinical outcomes of L4 subtypes in patients with Crohn′s disease
Xiao ZHU ; Yu ZHANG ; Qian CAO ; Yangbo LYU ; Jianguang XU
Journal of Chinese Physician 2024;26(9):1333-1337
Objective:To investigate whether there are differences in disease outcomes among patients with Crohn′s disease (CD) L4 subtype.Methods:A total of 488 CD patients who were initially diagnosed at the Quzhou People′s Hospital and the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from January 2017 to December 2019 were collected. They were divided into L4a, L4b, and non-L4 groups based on disease site classification, and the differences in intestinal complications and first abdominal surgery rates among the three groups were compared.Results:Among the 488 CD patients included in the study, 196(40.2%) were classified as L4 type, with L4b type being the predominant type (28.3%, 138/488). By confirming the time-dependent receiver operating characteristic (ROC) curve, the disease site can predict the surgical rate during follow-up of CD patients. Compared with non-L4 patients, L4b patients had a higher follow-up surgery rate [59.4%(76/128) vs 27.4%(80/292), P<0.001], while L4a patients had a lower rate [10.3%(6/58) vs 27.4%(80/292), P=0.009 6]. At the same time, the recurrence rate of intestinal obstruction in L4b patients during follow-up was significantly higher than that in L4a and non-L4 patients [46.9%(60/128) vs 6.9%(4/58), P<0.001; 46.9%(60/128) vs 11.6%(34/292), P=0.007]. The use of biologics can reduce the surgery rate in L4b patients ( HR: 1.93, 95% CI: 1.03-3.63, P=0.040 6). Conclusions:The incidence rate of L4b is high in newly diagnosed CD patients, and L4b is a high risk factor for poor prognosis of CD, so early use of biological agents is recommended. Accurate classification of disease sites can guide individualized clinical treatment.
9.Exploring effect of Grifola frondosa extract on inflammatory response of colonic tissue in rats with ulcerative colitis based on IL-6/JAK2/STAT3 signaling pathway
Xue JIN ; Xiande MA ; Zhuo ZHAO ; Ming XU ; Jianguang WANG ; Han DU ; Hongquan GUAN ; Xiaowei HAN
Chinese Journal of Immunology 2024;40(3):456-460,465
Objective:To investigate the effect and mechanism of Grifola frondosa extract on inflammatory response of colon tissue in rats with ulcerative colitis(UC)by regulating interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Forty SD rats were randomly divided into blank control group,UC model group,Grifola frondosa treatment group,western medicine treatment group and combined treatment group,with 8 rats in each group.After UC rats were established by free drinking 3%DSS for 7 days,the treatment group were given Grifola frondosa extract 10 mg/(kg·d),sulfasalazine 0.3 g/(kg·d),and the same amount of two drugs,for 14 consecutive days.During the experiment,general state of rats were observed,and the disease activity index(DAI)score was calculated;pathological changes of rats colon tissue were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue were detected by Western blot;content of IL-6 in rats serum was detected by ELISA;protein contents and expressions of IL-6R and MPO in rats colon tissue were determined by immunohistochemistry.Results:Compared with blank control group,general state of rats in UC model group was poor,DAI score was increased,obvious tissue mucosal defects and inflammatory cell infiltration were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue and contents of IL-6R and MPO were significantly increased(P<0.01);content of IL-6 in rats serum was significantly increased(P<0.01),the difference was statistically significant.Compared with UC model group,general condition of rats in each treatment group was improved,DAI score was decreased,HE staining showed that mucosal defects were improved to varying degrees,and occasionally inflammatory cell infiltration was observed;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in colon tissue were significantly decreased(P<0.01),contents of IL-6R and MPO in colon tissue and content of IL-6 in serum were significantly decreased(P<0.01 or P<0.05),the differences were statistically significant.Conclusion:Grifola frondosa extract can reduce the inflammatory response in colon tissue of UC rats by regulating expressions of IL-6/JAK2/STAT3 signaling pathway related factors.
10.Influence of infection frequency and vaccination on virus mutation of SARS-CoV-2
Guo XU ; Huan FAN ; Jianguang FU ; Huiyan YU ; Fei DENG ; Zhuhan DONG ; Shihan ZHANG ; Fengcai ZHU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Experimental and Clinical Virology 2024;38(5):481-488
Objective:To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods:The whole genome sequencing sequences of 2 659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis, and relevant information such as demographic and clinical characteristics were collected, and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.Results:The average age of these infected patients was 55.0 (31.0, 74.0) years, 1 150 cases (43.2%) in the age group of ≥60 years, 1 367 cases (51.4%) were males, 2 044 cases (76.9%) had a history of COVID-19 vaccination, and 1 629 cases (61.3%) had the first-time infection. The clinical symptoms of the infected patients were mainly mild, with a total of 2434 cases (91.5%), and 29 cases (1.1%) with severe symptoms or more. The average substitution rate of SARS-CoV-2 was 9.69 (9.38, 9.98)×10 -4 subs/site/year, and the dN/dS value of the S gene was 6.08 (5.56, 8.66), which was significantly greater than that of 1 ( P<0.001), indicating positive selection. The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection, aged 20-30 years, ≥60 years, and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above. Those with a history of vaccination and reinfection, aged 50-60 years old, ≥60 years old have smaller S gene dN/dS. Conclusions:Under the immune pressure exerted by vaccination and infection, the genome-wide mutation of SARS-COV-2 accelerated, but the non-synonymous mutation rate of the S gene decreased. The mechanism causing these phenomena needs further study.


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