BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Objective To compare the application of two endoscopic retrograde appendicitis therapies(ERAT)in acute uncomplicated appendicitis.Methods 100 patients with acute uncomplicated appendicitis from January 2021 to Jun 2023 were randomly divided into the direct vision group(50 cases)and the control group(50 cases).The control group was treated with conventional ERAT,and the direct vision group was treated with EyeMax Insight pancreaticobiliary imaging system assisted ERAT.The operation time,appendiceal intubation time,success rate of appendiceal intubation,abdominal pain relief time,body temperature recovery time,white blood cell recovery time,hospitalization time,and incidence of surgical complications were compared between the two groups.Results Comparison of appendiceal intubation time and operation time between the two groups:The appendiceal intubation time(5.43±3.51)min and operation time(45.50±10.65)min in the direct vision group were shorter than those in the control group(8.76±5.43)min and(54.32±13.45)min,and the differences were statistically significant(P=0.000).There were no significant differences in the success rate of intubation,recurrence rate,abdominal pain relief time,body temperature recovery time,white blood cell recovery time,hospitalization time and incidence of surgical complications between the two groups(P>0.05).Conclusion ERAT assisted by EyeMax Insight pancreaticobiliary imaging system can shorten the time of appendiceal intubation and operation,without increasing the incidence of complications,avoiding radiation exposure for patients and medical staff.It is safe and effective and worthy of clinical promotion.

A 68-year-old patient with non-small cell lung squamous carcinoma who received 6 cycles of sintilimab combination chemotherapy and sintilimab 200 mg,ivd,monotherapy developed severe diarrhea,abdominal pain,blood in the stool and other discomforts,and ultrasound and colonoscopy demonstrated extensive congestion and inflammation in the intestinal tract,and the pathologic biopsy was comprehensively considered to be an acute immune enteritis.Immunotherapy was suspended,adequate glucocorticoids and symptomatic treatment were given,and the patient's diarrhea and blood in stool improved after 2 days,and the symptoms were relieved and returned to normal after 6 days.The association between the patient's immune enteritis and sintilimab was assessed as probably relerant.This article reviews the literature on the case of immune-associated enteritis caused by sintilimab,describes how to use experimental methods and enteroscopy to detect the pathological changes in the clinic;and combines them with the clinical manifestations of diarrhea and blood in the stools to make the diagnosis and differentiation;and then refers to the guideline grading for timely management;and discusses the case to improve the clinicians'ability to recognize and deal with the relevant scenarios.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective    To evaluate the learning curve of CT-guided medical glue localization for pulmonary nodule before video-assisted thoracic surgery (VATS). Methods    The clinical data of the patients with pulmonary nodules who underwent CT-guided medical glue localization before VATS in our hospital from July 2018 to March 2021 were retrospectively analyzed. The patients were divided into 3 groups: a group A (from July 2018 to August 2019), a group B (from September 2019 to June 2020) and a group C (from July 2020 to March 2021). The localization time, morbidity, complete resection rate and other indexes were compared among the three groups. Results    A total of 77 patients were enrolled, including 24 males and 53 females aged 57.4±10.1 years. There were 25 patients in the group A, 21 patients in the group B, and 31 patients in the group C. 77 pulmonary nodules were localized. There was no significant difference among the groups in the basic data (P>0.05). The localization time in the group C was 10.6±2.0 min, which was statistically shorter than that in the group A (15.4±4.4 min) and group B (12.9±4.3 min) (P<0.01). The incidence of complications in the group C was lower than that in the group A and group B (25.8% vs. 52.0% vs. 47.6%, P=0.04). The success rate of localization of the three groups was not statistically different (P=0.12). Conclusion    There is a learning curve in CT-guided medical glue localization for single pulmonary nodule before VATS. After the first 46 cases, the operation time can be shortened, and the incidence of complications can be decreased.

【Objective】 To evaluate the efficacy and safety of different doses and frequencies of oral Sildenafil in the treatment of erectile dysfunction (ED). 【Methods】 The randomized,open clinical trial included 120 ED patients who met the inclusion and exclusion criteria. The patients were randomly divided into the following groups:on-schedule (25 mg/day),on-demand (50 mg,taken irregularly half an hour before each sexual life),new regular group (25 mg/day,50 mg more before each sexual life),regular group (100 mg/time,twice/week). All treatments lasted for 8 weeks. The follow-up indexes included the five-item International Index of Erectile Function (IIEF-5),Erection Hardness Scale (EHS) and Sexual Encounter Profile (SEP2/3). The adverse reactions were recorded. 【Results】 The IIEF-5 scores of the four groups were significantly higher than those after baseline treatment (P<0.001),but there was no significant difference among the four groups (P>0.05). In terms of effective rate,at the 16th week,there were significant differences between the on-demand group (10.7%) and new regular group (62.1%),and between the on-demand group (10.7%) and regular group (50.0%) (P<0.001). In terms of EHS, the percentage of grade 4 patients in regular group was significant higher than that in the on-demand group at the 8th week and 16th week (all P<0.05). In terms of positive rate of SEP-3,there was a significant difference between the on-demand group and regular group (P=0.042) at the 16th week. In the course of treatment,there were transient adverse reactions such as headache,blurred vision,stuffy nose and back pain,which did not affect the treatment. 【Conclusion】 All of the four treatment methods of oral sildenafil showed good efficacy. Both regular group and new regular group maintained good clinical efficacy during the follow-up,which is better than that of the on-demand group. The new regular scheme can be used as a new,safe and effective treatment option.

Objective:To investigate the diagnostic value of erythrocyte sedimentation rate/C-reactive protein (ECR), fibrinogen and D-dimer in periprosthetic infection after artificial knee replacement.Methods:A total of 205 patients, including 62 males and 143 females, aged 66.9±9.5 years (range 26-84 years), who underwent revision of artificial knee joint at Department of Joint Surgery, The First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2021 were retrospectively collected.122 cases of periprosthetic joint infection (PJI), including 43 cases of acute infection; 79 cases of chronic infection (13 cases of chronic infection combined with rheumatoid arthritis were analyzed separately); there were 83 cases without PJI, including 73 cases of aseptic loosening, 8 cases of prosthesis dislocation and 2 cases of joint stiffness. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, fibrinogen and D-dimer levels were examined before surgery, and the sensitivity and specificity of the indicators were calculated using the receiver operating characteristic (ROC) curve. The diagnostic value of different inflammatory markers was compared according to the area under curve (AUC).Results:The levels of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in acute PJI group were 2.47±2.91, 50 (38, 62) mm/1 h, 31.6 (13.9, 79.3) mg/L, 4.25±0.94 g/L, 763 (453, 1 157) ng/ml, respectively. The chronic PJI group was 3.06±2.95, 50 (34, 64) mm/1 h, 20.4(12.7, 43.3) mg/L, 4.19±0.91 g/L, 586 (317, 1 122) ng/ml, and the non-PJI group was 6.20±4.64, 22 (15, 34) mm/1 h, 4.6 (2.7, 7.74) mg/L, 3.10±0.59 g/L and 363 (181, 591)ng/ml were statistically significant ( P<0.05). The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and D-dimer in the acute PJI group were 0.82, 0.85, 0.90, 0.88, and 0.76, respectively.The optimal critical values were 2.89, 37.00 mm/1 h, 13.6 mg/L, 3.86 g/L, and 443.0 ng/ml, respectively, with sensitivity of 76.7%, 79.1%, 76.7%, 69.8%, and 82.4%, and specificity of 79.5%, 78.3%, 94.0%, 94.0%, 90.4%, and 63.8%, respectively. The AUC of ECR, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, D-dimer, and white blood cell count in the chronic PJI group were 0.77, 0.82, 0.87, 0.85, 0.67, and 0.63, respectively. The optimal critical values are 2.91, 33.00 mm/1 h, 10.9 mg/L, 4.01 g/L, 558.5 ng/ml, and 5.575×10 9 /L, respectively, with sensitivity of 68.2%, 78.8%, 81.8%, 63.6%, 57.9%, and 75.8%, and specificity of 79.5%, 73.5%, 88.0%, 95.2%, 72.5%, and 49.4%, respectively. Conclusion:Fibrinogen has a higher diagnostic value for knee joint PJI, followed by ECR, and D-dimer has the lowest diagnostic value for knee joint PJI.

Objective:To investigate the gender differences in serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet (PLT), fibrinogen (FIB) and D-dimer for the diagnosis of chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision arthroplasty in the Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to gender and diagnosis, they were divided into four groups: 78 cases of male chronic PJI, 108 cases of male aseptic loosening, 95 cases of female chronic PJI, and 189 cases of female aseptic loosening. The serological results of CRP, ESR, PLT, FIB and D-dimer were collected before operation. The receiver operating characteristics (ROC) curves were used to determine the optimal cut-off values of CRP, ESR, PLT, FIB and D-dimer for the diagnosis of chronic PJI in different genders, and to calculate their sensitivity and specificity. The diagnostic efficacy of the index was analyzed by comparing the area under curve (AUC) of different indicators.Results:The levels of ESR, PLT and D-dimer in the male chronic PJI group were 43 (20.0, 52.5) mm/1 h, 249×10 9 (204×10 9, 306×10 9) /L, 449 (219,833) μg/L, respectively, which were lower than those in the female group of 56 (40, 65) mm/1 h, 295×10 9 (228×10 9, 364×10 9) /L, and 645 (345, 1 157) μg/L, with statistically significant differences ( Z=-4.17, P<0.001; Z=-2.17, P=0.030; Z=-2.82, P=0.005). The AUC of CRP in the male chronic PJI group was 0.841, which was higher than the AUC of the other four indicators; CRP was combined with ESR, PLT, FIB and D-dimer to establish a joint prediction model for male chronic PJI. The ROC curve showed that the combination of CRP+FIB had a maximum AUC [0.849, 95% CI (0.79, 0.91)], sensitivity of 80% and specificity of 86%. The AUC of CRP in the female chronic PJI group was 0.866, which was higher than the AUC of the other four indices; CRP was combined with ESR, PLT, FIB and D-dimer to establish a combined prediction model for female chronic PJI. The ROC curve showed that the combination of CRP+PLT had the maximum AUC [0.883, 95% CI (0.84, 0.93)], sensitivity of 87% and specificity of 79%. Conclusion:Serologic indicators in patients with chronic PJI are gender-specific. CRP combined with FIB has the highest diagnostic value for the chronic PJI in males, while CRP combined with PLT has the highest diagnostic value for the chronic PJI in females.

Objective:To investigate the diagnostic value of plasma fibrinogen (FIB) in chronic periprosthetic joint infection (PJI).Methods:A total of 470 patients who underwent revision hip and knee arthroplasty after primary hip and knee arthroplasty in the First Affiliated Hospital of Xinjiang Medical University from January 2013 to December 2021 were retrospectively analyzed. According to the diagnosis of the disease, 173 patients (112 hips and 61 knees) were divided into chronic PJI group, including 78 males and 96 females, aged 65 (53, 72) years; and 297 patients (216 hips and 81 knees) were divided into aseptic loosening group, including 108 males and 189 females, aged 63 (50, 72) years. The preoperative levels of FIB, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer and platelet were compared between the two groups, and the sensitivity and specificity of the diagnosis of chronic PJI were calculated. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of FIB, CRP, ESR, platelet and D-dimer for the diagnosis of chronic PJI. The diagnostic efficacy of each indicator was analyzed by comparing the area under curve (AUC) and using a combined diagnostic test.Results:FIB, CRP, ESR, platelets and D-dimer in the chronic PJI group were 4.05 (3.52, 4.72) g/L, 19.5 (10.7, 40.0) mg/L, 50 (28, 60) mm/1 h, 270 (221, 351)×10 9 /L, 514 (261, 873) μg/L, respectively, which were higher than 3.25 (2.80, 3.63) g/L, 3.7 (2.0, 6.7) mg/L, 20 (12, 30) mm/1 h, 225 (182, 269)×10 9 /L, and 310 (167, 569) μg/L in sterile loosening group, with statistically significant differences ( P<0.05). The AUC of FIB, CRP, ESR, platelets and D-dimer in the diagnosis of chronic PJI were 0.78 (95% CI: 0.73, 0.82), 0.86 (95% CI: 0.82, 0.89), 0.80 (95% CI: 0.76, 0.85), 0.68 (95% CI: 0.63, 0.73), 0.64 (95% CI: 0.59, 0.69); the optimal cut-off values were 3.73 g/L, 9.64 mg/L, 39 mm/1 h, 280×10 9 /L, 624 μg/L; the sensitivity was 68%, 79%, 69%, 47%, 43%; the specificity was 81%, 85%, 85%, 81%, 79%, respectively. When CRP, ESR, FIB, platelets and D-dimer were combined sequentially to diagnose patients with chronic PJI, the sensitivity and specificity of the series test were 12.7% and 99.7%, and those of the parallel test were 100% and 37.3%. The combined diagnostic test showed that the maximum AUC of FIB combined with CRP was 0.85 (95% CI: 0.81, 0.89), with a sensitivity of 76% and a specificity of 89%. Conclusion:The clinical value of plasma FIB in the diagnosis of chronic PJI is not superior to that of CRP and ESR, but the combination of FIB and CRP can improve the specificity.

【Objective】 To analyze the mental health status and influencing factors of China medical team （CMT） members in Africa during COVID-19 pandemic. 【Methods】 From July 2021 to August 2021， 72 members of the 8th CMT in Malawi， the 36th CMT in Sudan and the 22nd CMT in Zambia were tested by 12-item General Health Questionnaire （GHQ-12）， Generalized Anxiety Disorder-7 （GAD-7）， and Patient Health Questionnaire-9（PHQ-9）， general information form and influencing factors form. 【Results】 The results of GHQ-12 were positive for 33.3% （24/72） of the CMT members. 51.4% （37/72） of the CMT members showed different levels of anxiety： 40.3% （29/72） of them had mild anxiety， 8.3% （6/72） of them had moderate anxiety， and 2.8% （2/72） of them had severe anxiety. 52.8% （38/72） of the CMT members had different degrees of depression： 34.7% （25/72） of them had mild depression， 11.1% （8/72） of them had moderate depression， 4.2% （3/72） of them had moderate-severe depression， and 2.8% （2/72） of them had severe depression. The CMT members who contacted with COVID-19 patients got significantly high scores of GHQ-12， GAD-7 and PHQ-9 （P<0.05） compared to those who did not have contact with COVID-19 patients. And CMT members who did not adapt to the local social life got significantly higher scores than those who adapted to the local social life （P<0.05）. These factors were the main factors affecting the mental health of the CMT members. 【Conclusion】 During COVID-19， the psychological pressure of CMT members was increased significantly， and both the incidence and severity of anxiety and depression were increased. Paying attention to and improving CMT members’ mental health status can ensure the smooth development of medical aid to Africa.