1.Antisense oligonucleotides targeting IRF4 alleviate psoriasis.
Yanxia YU ; Yirui WANG ; Weiwei CHEN ; Chang ZHANG ; Zhuo LI ; Jing YU ; Minhao WANG ; Can SONG ; Sihao YAN ; Jiayi LU ; Liangdan SUN
Acta Pharmaceutica Sinica B 2025;15(7):3575-3590
Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4+ (CD4+) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 -/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4+ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.
2.Molecular evolution of human infection with H9N2 subtype avian influenza virus in Anhui province from 2013 to 2022
Yidan XIA ; Sitian YANG ; Minhao HU ; Xue ZHOU ; Junling YU ; Wanrong LUO ; Weixi FANG ; Jun HE
Chinese Journal of Experimental and Clinical Virology 2024;38(5):527-532
Objective:To analyze the genetic and molecular characteristics of H9N2 subtype avian influenza viruses from external environment and humans in Anhui Province from 2013 to 2022.Methods:Environmental samples and human samples were collected from Anhui influenza surveillance network laboratory. Sixty-three strains of virus were isolated in chicken embryos. RT-PCR was used to amplify the virus and whole genome sequencing was performed. To construct gene evolutionary tree and analyze its genetic characteristics and potential glycosylation sites.Results:The hemagglutinin (HA) gene belongs to the 9.2.4.5 clade, and the protein cleavage sites are mostly " PSRSSR\GL". The neuraminidase (NA) gene, basic protein-1(PB1) gene, acidic protein (PA) gene, non-structural protein (NS) gene and nucleoprotein (NP) gene belong to the F/98 clade, the matrix protein (MP) gene belongs to the G1/97 clade, and the basic protein-2 (PB2) gene belongs to the ST/7488 clade. Mutations of T155N, R164Q, H183N, T189D/V, A190V/T and Q226L occurred in HA protein, deletion of NA protein occurred at 62-64 sites, and mutations of T271A, I292V/M and E627V/L occurred in PB2 protein. At the same time, mutations of K356R and S409N occurred in the PA protein.Conclusions:The H9N2 subtype avian influenza viruses collected from external environment and human sources in Anhui province from 2013 to 2022 belong to the same evolutionary branch, and amino acid site mutations suggest that the virus shows a tendency to gradually adapt to the mammalian host environment. Therefore, further studies on the adaptive evolution of the virus and related monitoring work are needed.
3.Epidemiological characteristics and analysis of related infection risk factors for influenza in Anhui Province from 2013 to 2021
Sitian YANG ; Wanrong LUO ; Minhao HU ; Junling YU ; Xue ZHOU ; Dexi LI ; Minghua ZHOU ; Jiawen ZHAO ; Xin'er HUANG ; Jun HE
Chinese Journal of Epidemiology 2023;44(8):1237-1244
Objective:Analysis of the characteristics of influenza epidemic in Anhui Province and quantification of the impact of different factors on influenza occurrence, providing scientific basis for better influenza prevention and control.Methods:Descriptive analysis and factor analysis were conducted on influenza-like illness (ILI) cases and RT-PCR results in Anhui Province from 2013 to 2021 using data from China's Influenza Monitoring Information System.Results:The percentage of influenza-like illness (ILI%) of sentinel hospitals in Anhui Province from April 1, 2013 to March 31, 2021 was 3.80% (1 209 142/31 779 987), showing an overall increasing trend, with a relatively high proportion in 2017-2018 at 4.30% (191 148/4 448 211). The proportion of ILI cases in infants and young children aged 0-4 years was a relatively high at 54.14% (654 676/1 209 142), and the highest ILI% was observed in Fuyang City, Anhui Province (6.25%, 236 863/3 788 863). Laboratory monitoring results showed that the positive rate of ILI cases in sentinel hospitals in 8 influenza monitoring years was 16.38% (34 868/212 912), showing an increasing trend year by year, with a relatively proportion in 2017-2018 at 26.19% (6 936/26 488). The detection rate of school-age children aged 5-14 years was a relativelyhigh at 28.81% (13 869/48 144), and the positive rate was a relatively high in Wuhu City among the 16 cities, reaching 22.01% (2 693/122 237). Influenza activity showed a single peak in winter-spring and alternating double peaks in winter-spring and summer, with different subtypes alternating, and A (H3N2) was the dominant subtype in summer. The results of a multiple logistic regression model showed that the positive rate was higher in 2017-2018, among children aged 5-14 years, in winter, and in southern Anhui.Conclusions:Influenza epidemic in Anhui Province has a clear seasonal pattern, and the ILI% and detection rate have shown an upward trend from 2013 to 2021. Therefore, it is suggested to ensure vaccine supply before the winter-spring influenza season arrives, and to strengthen vaccine uptake and health education to avoid the risk of infection during the peak period of influenza.
4.Comparison of isolating influenza virus in culture systems of adherent and a suspending cells of MDCK cell line
Xue ZHOU ; Junling YU ; Sitian YANG ; Yidan XIA ; Wanrong LUO ; Weixi FANG ; Minhao HU ; Jun HE
Chinese Journal of Experimental and Clinical Virology 2023;37(6):637-642
Objective:To compare the differences between suspension and adherent cells of MDCK cell line in the isolation of influenza virus, and to explore the application prospects of MDCK cell suspension.Methods:Determination of viable cell density and cell specific growth rate were recorded by cell count. The WHO recommended vaccine strains were used for virus infection experiments. After five passages, hemagglutination titers were detected, while the sequencing analysis of their HA and NA genes revealed the mutation frequency.Results:The 24-hour and 48-hour viable cell density of the cell suspension was more stable than that of adherent cells. The cell suspension achieved an HA titer of 1∶256 or higher in the third generation, while adherent cells had no titer. In the fourth and fifth generations, one amino acid site mutation was found in the HA gene of H3N2 and BV subtypes of influenza virus cultured in the cell suspension, while no gene mutation was found in adherent cells in two passages. There were no mutations in the whole NA gene.Conclusions:Suspension of MDCK cells have more stable growth and higher efficiency in virus isolation than adherent cells, meanwhile there was a low rate of virus mutation during continuous passage. This study demonstrated the feasibility of this suspension of MDCK cells for influenza vaccine production based on cell culture technology.
5. Progress of Research on Factors Related to Therapeutic Effect of Perianal Fistulizing Crohn’s Disease
Chinese Journal of Gastroenterology 2022;27(1):47-51
Perianal fistulizing Crohn' s disease (pfCD) is the commonly seen perianal disease in Crohn's disease (CD), and its main treatment is the combined use of medical and surgical therapy on basis of radiological assessment. However, low response rate and high recurrence rate are found in clinical practice. It is of great importance to predict the therapeutic efficacy accurately according to the individual characteristics of patients for improving the prognosis of pfCD. This article reviewed the progress of research on factors related to the therapeutic efficacy of pfCD for helping to develop more specifically targeted treatment strategies.
6.Risk factors for anastomotic leakage after laparoscopic lower anterior resection of rectal cancer and application value of risk assessment scoring model: a multicenter retrospective study
Yang LUO ; Minhao YU ; Ran JING ; Hong ZHOU ; Danping YUAN ; Rong CUI ; Yong LI ; Xueli ZHANG ; Shichun FENG ; Shaobo LU ; Rongguo WANG ; Chunlei LU ; Shaojun TANG ; Liming TANG ; Yinxin ZHANG ; Ming ZHONG
Chinese Journal of Digestive Surgery 2021;20(12):1342-1350
Objective:To investigate the risk factors for anastomotic leakage after laparo-scopic lower anterior resection (LAR) of rectal cancer, and the application value of its risk assess-ment scoring model.Methods:The retrospective case-control study was conducted. The clinico-pathological data of 539 patients who underwent laparoscopic LAR of rectal cancer in 13 medical centers, including 248 cases in Renji Hospital of Shanghai Jiaotong University School of Medicine, 35 cases in Ningbo First Hospital, 35 cases in Changzhou Second People's Hospital, 32 cases in the First People's Hospital of Nantong, 32 cases in Linyi People's Hospital, 31 cases in Changzhou Wujin People's Hospital, 28 cases in Jiading District Hospital of Traditional Chinese Medicine, 27 cases in the First Hospital of Taizhou, 26 cases in Shanghai Pudong Gongli Hospital, 21 cases in the People's Hospital of Rugao, 11 cases in Central Hospital of Fengxian District, 7 cases in Ningbo Hangzhou Bay Hospital and 6 cases in Jiangsu jianhu People's Hospital, from January 2016 to November 2020 were collected. There were 157 males and 382 females, aged (62.7±0.5)years. Observation indicators: (1) follow-up; (2) risk factors for anastomotic leakage after laparoscopic LAR; (3) establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. Follow-up was conducted by outpatient examination or telephone interview. Patients were followed up at 1 week after discharge or 1 month after the operation to detect the anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test and multivariate analysis was conducted usong the Logistic regression model. The area under curve of receiver operating characteristic curve was used to estimate the efficiency of detecton methods. The maximum value of the Youden index was defined as the best cut-off value. Results:(1) Follow-up: 539 patients were followed up at postoperative 1 week and 1 month. During the follow-up, 79 patient had anastomotic leakage, with an incidence of 14.66%(79/539). Of the 79 patients, 39 cases were cured after conservative treatment, 40 cases were cured after reoperation (ileostomy or colostomy). (2) Risk factors for anastomotic leakage after laparoscopic LAR. Results of univariate analysis showed that sex, age, body mass index, smoking and/or drinking, tumor diameter, diabetes mellitus, hemoglobin, albumin, grade of American Society of Anesthesio-logists (ASA), neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line, the number of pelvic stapler, reinforced anastomosis, volume of intraoperative blood loss, placement of decompression tube, preservation of left colic artery, operation time and professional doctors were related factors for anastomotic leakage after laparoscopic LAR ( χ2=14.060, 4.387, 5.039, 4.094, 17.488, 33.485, 25.066, 28.959, 34.973, 34.207, 22.076, 13.208, 16.440, 17.708, 17.260, 4.573, 5.919, 5.389, P<0.05). Results of multivariate analysis showed that male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decom-pression tube were independent risk factors for anastomotic leakage after laparoscopic LAR ( odds ratio=2.864,3.043,12.556,7.178,8.425,12.895,8.987,4.002,3.084,4.393,3.266,3.224,95% confidence interval as 1.279?6.411, 1.404?6.594, 4.469?35.274, 2.648?19.459, 2.471?28.733, 4.027?41.289, 3.702?21.777, 1.746?9.171, 1.365?6.966, 1.914?10.083, 1.434?7.441, 1.321?7.867, P<0.05). (3) Establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. based on the results of univariate analysis, clinicopathological factors with χ2>20, χ2>10 and ≤20 or χ2≤10 were defined as scoring of 3, 2, 1, respectively. The cumulative clinicopatho-logical factors scoring ≥6 was defined as an effective evaluating indicator for postoperative anastomotic leakage. The risk assessment scoring model (6-321) for anastomotic leakage after laparoscopic LAR was established. The cumulative value ≥6 indicated high incidence of anastomotic leakage, and the cumulative value <6 indicated low incidence of anastomotic leakage. Conclusions:Male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neo-adjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decompression tube are independent risk factors for anastomotic leakage after laparoscopic LAR. The risk assessment scoring model (6-321) is established according to the above results.The cumulative value ≥6 indicates high incidence of anastomotic leakage and the cumulative value <6 indicates low incidence of anastomotic leakage.
7.Application value of barbed suture in reinforcing anastomosis during laparoscopic radical resection of rectal cancer
Yang LUO ; Minhao YU ; Jianjun CHEN ; Jun QIN ; Shaolan QIN ; Yizhou HUANG ; Ming ZHONG
Chinese Journal of Digestive Surgery 2020;19(11):1205-1210
Objective:To investigate the application value of barbed suture in reinforcing anastomosis during laparoscopic radical resection of rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 215 patients with rectal cancer who underwent laparoscopic radical resection in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2016 to December 2018 were collected. There were 122 males and 93 females, aged (62.3±0.7)years, with a range from 20 to 75 years. Of 215 patients, 86 patients undergoing laparoscopic radical resection of rectal cancer with barbed suture for anastomosis were allocated into barbed suture group, and 129 patients undergoing laparoscopic radical resection of rectal cancer without reinforced anastomosis were allocated into traditional group, respectively. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications, anastomotic healing and patency of patients up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Ordinal data were analyzed using the Friedman non-parametric test. Results:(1) Intraoperative situations: patients in the two groups underwent laparoscopic radical resection of rectal cancer successfully, without conversion to open laparotomy. The volume of intraoperative blood loss, operation time, distance between the anastomosis and dentate line, length of auxiliary incision of the barbed suture group were (127±9)mL, (160.2±3.8)minutes, (3.56±0.15)cm, (4.12±0.11)cm, respectively, versus (114±6)mL, (128.9±2.4)minutes, (3.67±0.12)cm, (4.25±0.09)cm of the traditional group. There was a significant difference in the operation time between the two groups ( t=7.33, P<0.05), but no significant difference in the other indicators between the two groups ( t=1.32, 0.61, 0.94, P>0.05). (2) Postoperative situations: the time to first flatus after surgery and duration of postoperative hospital stay of the barbed suture group were (72.5±2.2)hours and (8.1±0.5)days, respectively, versus (76.2±1.7)hours and (8.0±0.5)days of the traditional group, showing no significant difference between the two groups ( t=1.33, 0.87, P>0.05). (3) Follow-up: 215 patients were followed up for 6-12 months, with a median follow-up time of 8 months. In the barbed suture group, 2 patients had postoperative anastomotic leakage, 5 had urinary retention, 6 had incision infection, 4 had intestinal obstruction, 3 had bowel dysfunction in 6 months after operation. In the traditional group, 13 patients had postoperative anastomotic leakage, 15 had urinary retention, 11 had incision infection, 8 had intestinal obstruction, 9 had bowel dysfunction in 6 months after operation. There was a significant difference in the anastomotic leakage between the two groups ( t=4.77, P<0.05), but no significant difference in the urinary retention, incision infection, intestinal obstruction, bowel dysfunction in 6 months after operation between the two groups ( t=2.07, 0.17, 0.22, 1.26, P>0.05). Patients in the two groups showed unobstructed intestinal tract on enteroscopy. Conclusion:The barbed suture for reinforcing anastomosis in radical resection of rectal cancer is safe and feasible, which can reduce the incidence of anastomotic leakage.
8.Laparoscopic radical resection of rectal cancer with preservation of the left colic artery: anatomical basis and surgical experience
Ming ZHONG ; Yang LUO ; Minhao YU
Chinese Journal of Surgery 2020;58(8):600-603
In order to increase the blood supply of anastomosis, surgeons choose to preserve the left colon artery (LCA) during the laparoscopic radical resection of rectal cancer. However, surgeons are always ailed by hemorrhage and incompletely dissection of No. 253 lymph nodes. One reason is the shortage of understanding the relationship between inferior mesenteric artery (IMA), LCA, and inferior mesenteric vein before surgery. Another reason is that surgeon always remove the lymph nodes around LCA, while don′t normatively resect No. 253 lymph nodes, which affect the overall survival rate. Therefore, the "medial-to-lateral approach" for laparoscopic preservation with LCA radical resection in rectal cancer was suggested in this article. The CT technique could be used to analyze the IMA classification, which contribuated to the standard conservation of LCA. Laparoscopic radical resection of rectal cancer could be completed of high quality, through accurate definition and exactly dissection of the No. 235 lymph nodes.
9.Vertical supraumbilical incision versus left lower oblique incision for specimen retrieval during laparoscopic rectal surgery
Yang LUO ; Minhao YU ; Jianjun CHEN ; Jun QIN ; Ran CUI ; Yizhou HUANG ; Ming ZHONG
Chinese Journal of Gastrointestinal Surgery 2020;23(3):289-293
Objective:To compared the short-term surgical outcomes of the vertical supraumbilical incision with the left lower oblique incision for specimen retrieval in laparoscopic resection for rectal cancer.Methods:A retrospective cohort study was performed. Inclusion criteria: (1) rectal cancer confirmed by colonoscopy and pathological examination; (2) undergoing the operation for the first time; (3) laparoscopic rectal surgery performed by the same surgeon team; (4) age of > 18 years and < 76 years old. According to above criteria, clinical data of 178 consecutive patients scheduled for laparoscopic surgery for rectal cancer at Department of Gastrointestinal Surgery of Renji Hospital between March 2015 and December 2017 were collected. Based on incision site of the mini-laparotomy, patients were classified to the vertical supraumbilical incision group (n=75) and the left lower oblique incision group ( n=103). There were no significant differences in baseline data, such as age, gender, body mass index (BMI), tumor diameter, preoperative carcinoembryonic antigen (CEA) level, score of American Society of Anesthesiologists, TNM stage, between the two groups (all P>0.05). Perioperative variables and follow-up data were compared between two groups. Results:Between the vertical supraumbilical incision group and the left lower oblique incision group, the operation time [(131.7±3.7) minutes vs. (138.5±3.5) minutes], operative bleeding volume [(138.9±11.5) ml vs. (154.3±10.3) ml], length of auxiliary incision [(4.0±0.1) cm vs. (4.0±0.1) cm], and distance from anastomosis to dentate line [(3.8±0.1) cm vs. (4.2±0.1) cm] were not significantly different (all P>0.05). As compared to the left lower oblique incision group, patients in vertical supraumbilical incision group had earlier flatus [(62.7±2.3) hours vs. (69.2±1.7) hours, t=2.282, P=0.023], earlier ambulation [(41.9±1.8) hours vs. (46.78±1.42) hours, t=2.131, P=0.032], lower pain VAS scores at postoperative 24 hours (2.0±0.1 vs. 2.4±0.1, t=2.172, P=0.032) and 48 hours (2.7±0.1 vs. 3.0±0.1, P<0.05), and lower incidence of postoperative incisional hernia [6.7% (5/75) vs. 9.7% (10/103), χ 2=3.942, P=0.042]. However, the postoperative fluids intake time, hospitalization days, pain VAS scores at postoperative 12 hours and postoperative complications (wound infection, anastomotic leakage, urinary retention, intestinal obstruction) were not significantly different between the two groups (all P>0.05). Conclusion:The vertical supraumbilical incision in laparoscopic resection for rectal cancer can reduce the degree of postoperative pain, facilitate early recovery of intestinal function and decrease the incidence of incisional hernia.
10.Laparoscopic radical resection of rectal cancer with preservation of the left colic artery: anatomical basis and surgical experience
Ming ZHONG ; Yang LUO ; Minhao YU
Chinese Journal of Surgery 2020;58(8):600-603
In order to increase the blood supply of anastomosis, surgeons choose to preserve the left colon artery (LCA) during the laparoscopic radical resection of rectal cancer. However, surgeons are always ailed by hemorrhage and incompletely dissection of No. 253 lymph nodes. One reason is the shortage of understanding the relationship between inferior mesenteric artery (IMA), LCA, and inferior mesenteric vein before surgery. Another reason is that surgeon always remove the lymph nodes around LCA, while don′t normatively resect No. 253 lymph nodes, which affect the overall survival rate. Therefore, the "medial-to-lateral approach" for laparoscopic preservation with LCA radical resection in rectal cancer was suggested in this article. The CT technique could be used to analyze the IMA classification, which contribuated to the standard conservation of LCA. Laparoscopic radical resection of rectal cancer could be completed of high quality, through accurate definition and exactly dissection of the No. 235 lymph nodes.

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