[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

[The effect of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy].

Objective: To investigate the effects of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy. Methods: A total of 100 patients who were scheduled to undergo painless colonoscopy were selected as the study subjects and randomly divided into two groups by a computerized number method. Ten patients in both groups dropped out because of disruption of the study protocol, and 45 patients from each group were included in the final analysis. Before anesthesia induction, patients in group glycopyrrolate (group G) were injected with 0.2 mg glycopyrrolate, while those in congtrol group (group C) were injected with an equal amount of saline. The heart rate, systolic blood pressure, and diastolic blood pressure were recorded at T0 (baseline period), T1 (after anesthesia induction), T2 (colonoscopy over sigmoid colon), T3 (colonoscopy over the liver region), T4 (after the end of examination), and T5 (at the awakening phase), and the degree of intestinal spasm was assessed intraoperatively using the Likert's four-point scale. The numerical rating scale (NRS) was used to assess preoperative and postoperative pain. The incidence of adverse events was recorded. Results: The general data at baseline were not statistically different between the two groups (P>0.05). During the procedure, patients in group G had lower intraoperative intestinal spasm scores than those in group C (P=0.028). Intraoperative hypotension and bradycardia occurrence were lower in group G than in group C (P<0.05), and intraoperative norepinephrine use was also lower than in the group C (P=0.034). Postoperative visual analog scale pain scores were lower in group G (P=0.047), but patients who used glycopyrrolate had a higher proportion of dry mouth (P=0.035). Conclusion: During painless colonoscopy, preoperative administration of glycopyrrolate significantly improved intraoperative hemodynamic fluctuations, reduced the incidence of hypotension and bradycardia, and relieved postoperative pain. However, glycopyrrolate use resulted in the risk of dry mouth.

[Analysis of clinical characteristics of children with adenoid hypertrophy and pharyngolaryngeal reflux].

Objectives: To explore the clinical characteristics of children with adenoid hypertrophy (AH) and laryngopharyngeal reflux (LPR) by detecting the expression of pepsin in adenoids as a standard for AH with LPR. Methods: A total of 190 children who were admitted for surgical treatment due to AH were included in the study. The main clinical symptoms of the patients were recorded, and the degree of adenoid hypertrophy was evaluated. Before the surgery, Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were used to evaluate the reflux symptoms. After the surgery, pepsin immunohistochemical staining was performed on the adenoid tissue, and according to the staining results, the patients were divided into study group (pepsin staining positive) and control group (pepsin staining negative). SPSS 19.0 software was used for statistical analysis. Quantitative data conforming to normal distribution between the two groups were tested by two-independent sample t test, and quantitative data with skewed distribution were tested by Mann-Whitney U test. Results: The positive rate of pepsin staining in the 190 AH patients was 78.4% (149/190). The study group had higher levels of preoperative symptoms such as erythema and/or congestion of the pharynx(2.1±0.7 vs. 1.8±0.6,t=2.23), vocal cord edema[1.0(0, 1.0) vs. 1.0(0, 1.0), Z=2.00], diffuse laryngeal edema[0(0, 1.0) vs. 0(0, 0), Z=2.48], posterior commissure hypertrophy[(1.4±0.6 vs. 1.1±0.5), t=2.63], and a higher total score on the RFS scale than the control group(6.2±2.7 vs. 5.0±2.6, t=2.47), with statistical differences (P<0.05). The sensitivity and specificity of RFS score in diagnosing AH with LPR were 24.8% and 80.5%, respectively. When RFS>5 was used as the positive threshold, the sensitivity and specificity of RFS score in diagnosing AH with LPR were 61.1% and 58.5%, respectively. There was a statistical difference in the number of positive cases of RFS score between the study group and the control group(91 vs. 17,χ2=5.04,P=0.032). Conclusions: LPR is common in AH children. Children with AH and LPR have specific performance in electronic laryngoscopy, such as erythema with edema in the pharynx, posterior commissure hypertrophy, and vocal cord edema.

[Lower urinary tract injury in transvaginal reconstructive pelvic surgery].

Objective: To explore the characteristics, prevention and treatment strategies of lower urinary tract injury in transvaginal reconstructive pelvic surgery (vRPS). Methods: A retrospective analysis was conducted on 24 patients who suffered lower urinary tract injuries occuring in vRPS from January 2005 to June 2021, among which 4 cases were referred to our hospital from other hospitals. Results: (1) In our hospital, 1 952 patients underwent vRPS for anterior and (or) middle pelvic organ prolapse during that study period, with a 1.0% (20/1 952) incidence of lower urinary tract injuries occurring in 20 cases. (2) Ureteral injuries were observed in 14 cases who underwent transvaginal high uterosacral ligament suspension (1.4%, 14/966). The symptoms were relieved after the removal of sutures. (3) Bladder injuries occurred in 6 cases in our hospital, with 4 cases (0.7%, 4/576) in anterior transvaginal mesh surgery (aTVM), one (0.4%, 1/260) in colpocleisis, and one (0.7%, 1/150) in apical suspension for fornix prolapse. An additional 4 cases of bladder injury were referred to our hospital after aTVM. Among the 8 cases of bladder injury during aTVM, 2 cases were intraoperative incidents. Cystoscopy confirmed that the superficial branch or puncture rod of anterior vaginal mesh had penetrated into the bladder. Re-puncturing and placement of the mesh were successfully performed. No abnormalities were observed during a follow-up period of 4-5 years. Postoperative bladder injuries were identified in 6 cases, characterized by mesh erosion into the bladder and formation of calculi. These injuries were confirmed between 6 months to 2 years after vRPS. The exposed mesh and calculi in the bladder were removed through laparotomy or cystoscopy, followed up for 2-12 years. One case experienced slight re-erosion of mesh to the bladder. Conclusions: Lower urinary tract injuries are difficult to avoid in vRPS, particularly in transvaginal high uterosacral ligament suspension and aTVM. However, the incidence is low. Lower urinary tract injuries during vRPS could be easily detected and managed intraoperatively because of the use of cystoscopy. As long-term postoperative complications, erosion of transvaginal mesh to lower urinary tract postoperatively could be treated correctly, seldom with severe sequelae.

[The effects of nucleotide-binding oligomerization domain-like receptor 3 inflammasome on obstructive sleep apnea and its complications].

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.

Clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse.

OBJECTIVE: The aim of this study was to analyze the clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse (POP). PATIENTS AND METHODS: Sixty POP patients admitted to our hospital from January 2020 to December 2021 were picked and divided into Group A (laparoscopic Y-mesh, n = 20), Group B (laparoscopic sacrovaginal fixation, n = 20), and Group C (da Vinci robotic sacral fixation, n = 20). These three groups were compared in terms of the perioperative indexes, such as operation time, intraoperative blood loss, postoperative indwelling catheter days, anal exhaust time, postoperative hospitalization days, etc. The occurrence of short-term and long-term complications in the three groups was compared. The changes of the following index values in the POP quantification system (POP -Q) staging before and 1 year after surgery were recorded and compared among the three groups. It mainly includes the midline of the anterior vaginal wall at 3 cm from the hymenal margin (Aa), the farthest point of the anterior vaginal vault from point Aa (Ba), the farthest point of the ectocervix (C), the location of the posterior vaginal vault or rectal uterine trap (D), the midline of the posterior vaginal wall at 3 cm from the hymenal margin (Ap), and the reflection of the posterior vaginal vault at the farthest point from the Ap point (Bp) values. The changes in Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were recorded and compared before and 1 year after the operation. RESULTS: The patients in Group C had significantly lower intraoperative bleeding, postoperative indwelling catheter days, anal exhaust time, and postoperative hospitalization days compared with those in Group A and Group B (p < 0.05). There existed no statistical difference in the incidence of short-term and long-term complications between Group B and Group C (p > 0.05), but both were much lower than Group A (p < 0.05). The differences in POP-Q staging, PFDI-20 scale, and PISQ-12 scale were not statistically significant among the three groups before surgery (p > 0.05), and the POP-Q staging Aa, Ba, C, D, Ap, and Bp values, PFDI-20 scale, and PISQ-12 scale were strongly improved in three groups after the surgery (p < 0.05). However, the POP-Q staging, PFDI-20 scale, and PISQ-12 scale among the three groups had no obvious difference after the surgery (p > 0.05). CONCLUSIONS: The efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for POP was comparable to that of laparoscopic Y-mesh treatment and laparoscopic sacral vaginal fixation. However, da Vinci's robotic sacral fixation had the advantages of less intraoperative bleeding and faster postoperative recovery, which helped patients recover quickly and improved their quality of life.

[Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center].

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

[Several issues on surgical treatment for adenocarcinoma of esophagogastric junction].

There are several controversies and issues in the surgical treatment of esophagogastric junction (AEG) currently. The Siewert classification and TNM staging system are commonly used to assist clinical decision and prognosis prediction. Generally, transthoracic procedure is more suitable for Siewert Ⅰ type and longer esophageal invasion patients, while transhiatal is more suitable for Siewert Ⅲ type patients. The optimal extent of lymph node dissection for AEG should be based on tumor location and esophageal invasion range. The extent of surgical resection and the method of digestive tract reconstruction should be based on the principle of radical resection and surgical safety, and the postoperative life quality of patients should be fully considered. Roux-en-Y anastomosis is the most common and efficient anastomosis after total gastrectomy, while double tract anastomosis is recommended by many experts after proximal gastrectomy. With the continuous advancement of minimally invasive techniques, experienced centers and teams can perform digestive tract reconstruction under total laparoscopy. In the future, more high-quality studies are expected to provide evidence-based medical evidence for AEG's surgical treatment decisions.

[Prevalence of allergic rhinitis in Chinese children from 2001 to 2021: Meta analysis].

Objective: To analyze the prevalence of allergic rhinitis in Chinese children from 2001 to 2021, in order to provide data support for the prevention and treatment of allergic rhinitis in children. Methods: "Allergic rhinitis" "children" "adolescent" "infant" "prevalence" "epidemiology" were used in the main search terms. The combination of Mesh words and free words was adopted. CNKI, CBM, VIP, WanFang Data, PubMed, Web of Science, Embase and The Cochrane Library for publications between January 1, 2001 and December 31, 2021 were searched systemically and data were extracted from eligible studies by two independent reviewers. Supplementary collection was made by identifying retrospective references from the included literature. After study quality assessment, Meta analysis was completed using Stata 16.0 software. Results: A total of 20 cross-sectional studies were included, involving 54 886 cases. Meta analysis results showed that the overall prevalence of allergic rhinitis among the participants was 18.46% (95%CI:14.34%-22.59%). Subgroup analysis showed that the prevalence of allergic rhinitis from 2012 to 2021 (19.75%) was higher than that from 2001 to 2011 (14.81%), and the difference was statistically significant (P<0.001). The prevalence of different regions from high to low was East China (22.77%), North China (20.82%), Northwest China (17.77%), Central China (16.62%), Southwest China (16.33%), Northeast China (16.16%) and South China (7.29%) respectively, the difference was statistically significant (P<0.001). The prevalence of male (20.73%) was higher than that of female (16.34%), and the difference was statistically significant (P<0.001). The prevalence of Han nationality(17.31%) was higher than that of ethnic minorities (15.93%), and the difference was statistically significant (P<0.001). Conclusion: The prevalence of allergic rhinitis in Chinese children is high and the prevalence in children varies by publication year, region, sex and nationality.

ac4C acetylation of RUNX2 catalyzed by NAT10 spurs osteogenesis of BMSCs and prevents ovariectomy-induced bone loss.

N-acetyltransferase 10 (NAT10) is the key enzyme for N4-acetylcytidine (ac4C) modification of mRNA, which participates in various cellular processes and is related to many diseases. Here, we explore the relationships among osteoblast differentiation, NAT10, and ac4C, and we found that NAT0 expression and the ac4C level of total RNA were decreased in the bone tissues of bilateral ovariectomized (OVX) mice and osteoporosis patients. Adenoviruses overexpressing NAT10 reversed bone loss, and Remodelin, an NAT10 inhibitor, enhanced the loss of bone mass in OVX mice. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) with low-level ac4C modification formed fewer calcium nodules in vitro with NAT10 silencing, whereas BMSCs with high-level ac4C modification formed more calcium nodules with NAT10 overexpression. Moreover, we demonstrated that the ac4C level of runt-related transcription factor 2 (RUNX2) mRNA was increased after BMSCs were cultured in osteogenic medium (OM) and decreased after NAT10 silencing. The RUNX2 mRNA half-life and protein expression decreased after silencing NAT10 in BMSCs. Therefore, NAT10-based ac4C modification promotes the osteogenic differentiation of BMSCs by regulating the RUNX2 ac4C level. Because abnormal levels of NAT10 are probably one of the mechanisms responsible for osteoporosis, NAT10 is a new potential therapeutic target for this disease.

[Effectiveness of abdominal minimal incision sacrocolpopexy for advanced pelvic organ prolapse].

Objective: To evaluate the indications, surgical skills and clinic outcomes of abdominal minimal incision sacrocolpopexy (AMISC) for treatment of advanced pelvic organ prolapse (POP). Methods: The retrospective study analyzed 30 women with advanced POP who underwent AMISC between June 2016 and October 2019, including 9 cases of recurrent prolapse and 10 cases of vault prolapse. AMISC was especially applicable to: (1) patients with several medical complications who was unable to tolerate general anesthesia or laparoscopic surgery, but able to tolerate combined spinal-epidural anesthesia and open surgery; (2) other abdominal procedures were indicated to perform with AMISC simultaneously, such as myomectomy, subtotal hysterectomy etc, the specimens were easy to get out of the abdominal cavity and morcellation was avoided; (3) surgeons preferring open surgery to laparoscopic surgery or skilled in open surgery; (4) patients with prior pelvic operations, presenting severe abdominal and pelvic adhesions. Objective outcomes were assessed by pelvic organ prolapse quantification (POP-Q) system. Subjective outcome were assessed by pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form (PFIQ-7) and patient global impression of improvement (PGI-I). Results: All patients with 1-3 medical complications were successfully performed with AMISC without stopping procedure, enlarging the incision or changing to other procedure, the operation duration was (110±19) minutes. The mean time of follow-up was (33.5±12.4) months (range: 8-49 months). The postoperative points of Aa, Ba, C, Ap, Bp reduced significantly and point C improved from (2.33±2.50) cm to (-7.54±1.18) cm after AMISC (P<0.01). The objective cure rates were both 100% (30/30) in apex and posterior compartment, while 97% (29/30) in anterior compartment. Postoperative scores of PFDI-20 and PFIQ-7 were all significant decreased (all P<0.01). About PGI-I, 29 patients chose "significant improvement", subjective satisfaction was 97% (29/30). Anterior sacral plexus hemorrhage occurred in 2 cases (7%, 2/30). There was no intestinal obstruction or injury of bladder, bowel and ureter intra- and postoperation. Two cases (7%, 2/30) had mesh exposure. Conclusion: AMISC is a safety, convenient, minimal traumatic and durable procedure for apical prolapse with short learning curve in the most of cases.

Baicalin attenuates lipopolysaccharide-induced renal tubular epithelial cell injury by inhibiting the TXNIP/NLRP3 signalling pathway via increasing miR-223-3p expression.

Baicalin has been used in China to treat inflammation-related diseases, such as inflammation-induced acute kidney injury (AKI). However, the specific mechanism of baicalin remains unclear. To observe the protective effects of baicalin on lipopolysaccharide (LPS)-induced inflammatory injury of renal tubular epithelial cells (HK-2 cells) and to explore its protective mechanism. LPS (1 mg/L) was used to induce an HK-2 cell inflammatory injury model in vitro. The cells were divided into seven groups: the normal control group, LPS-induced group, LPS plus 5 µmol/L baicalin treatment group, LPS plus 15 µmol/L baicalin treatment group, LPS plus 25 µmol/L baicalin treatment group, LPS plus 50 µmol/L baicalin treatment group, and LPS plus 75 µmol/L baicalin treatment group. 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide (MTT) assay was employed for detecting the relative survival rate of HK-2 cells. Enzyme-linked immunosorbent assay was used for detecting the levels of inflammatory factors, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). Moreover, the expression of inducible nitric oxide synthase (iNOS); cyclooxygenase-2 (COX-2); nuclear factor kB65 (NF-κB65); phosphorylated NF-κB inhibitory protein-α (p-IκB-α); NF-κB inhibitory protein (IκB); human thioredoxin interacting protein (TXNIP); and human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) were determined by Western blot analysis. The expression levels of NLRP3 and TXNIP mRNA and miR-223-3p were determined by RT-PCR. Results found that the relative survival rate of HK-2 cells treated with different baicalin concentrations was significantly increased (P<0.05) and the levels of the inflammatory factors IL-6, IL-1ß, and TNF-α were significantly decreased (P<0.05) compared with those of the LPS-induced group. The expression levels of the inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2 and the genes expressions of TXNIP and NLRP3 were significantly decreased in the cells (P<0.05), while the expression level of miR-223- 3p was significantly increased (P<0.05). These changes were induced in a dose-dependent manner. The results suggest that baicalin significantly inhibited the expression of inflammation-related proteins and alleviated LPS-induced inflammatory injury in HK-2 cells. The mechanism may be associated with the inhibition of activation of the TXNIP/NLRP3 inflammatory pathway, which might be mediated by increased expression of miR-223-3p. Thus, NLRP3 is a regulatory target of miR-223-3p.

[Preliminary clinical analysis of direct renin inhibitor aliskiren in the treatment of severe coronavirus disease 2019 patients with hypertension].

Objective: To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension. Methods: The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension. Results: Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged. Conclusion: Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.

miRNA-217 inhibits proliferation of hepatocellular carcinoma cells by regulating KLF5.

OBJECTIVE: The aim of this study was to figure out the effect of microRNA-217 on the proliferation of hepatocellular carcinoma (HCC) cells, and to explore its influence on KLF5 expression and the underlying regulatory mechanisms. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-217 in tumor tissues and paracancerous tissues of 60 patients with HCC. Meanwhile, the relationship between microRNA-217 expression and HCC pathological parameters was analyzed. In HCC cell lines, including HepG2 and Bel-7402, negative control group (NC) and microRNA-217 overexpression group were set up, and qRT-PCR was performed to further verify their transfection efficiency. In addition, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the effect of microRNA-217 on the biological function of HCC cells. Finally, the potential mechanism of KLF5, the downstream gene of microRNA-217, was explored using bioinformatics analysis and cell recovery experiments. RESULTS: QRT-PCR results showed that microRNA-217 level in tumor tissues of HCC patients was conspicuously lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-217, the pathological stage was higher and the overall survival rate was lower in patients with low expression. Compared with the NC group, the cell proliferation ability of the microRNA-217 mimics group was conspicuously decreased. Subsequently, in the HCC cell line and tissue verification, the expression of KLF5 was found remarkably increased, and microRNA-217 exhibited a negative correlation with KLF5 level. In addition, the overexpression of microRNA-217 conspicuously reduced the protein expression of CD31, Ki-67, c-Myc, MMP-2, and MMP-9. In cell recovery experiment, it was found that the overexpression of KLF5 could counteract the effect of microRNA-217 mimics on the cell proliferation of HCC, thereby inhibiting the malignant progression of this disease. CONCLUSIONS: The above studies demonstrated that microRNA-217 was markedly associated with the pathological stage and poor prognosis of HCC, and could inhibit the malignant progression of this disease. In addition, our investigation has showed that microRNA-217 might be capable of inhibiting cell proliferation of HCC via regulating KLF5.

[A five-year analysis of effect on transvaginal high uterosacral ligament suspension with or without native-tissue repair for middle compartment defect].

Objective: To assess the five-year effect of the transvaginal high uterosacral ligament suspension (HUS) with or without additional concomitant native-tissue anterior and (or) posterior repair in women suffering from middle compartment defect. Methods: A retrospective review of records identified 79 women who underwent transvaginal HUS with or without additional concomitant native-tissue anterior and (or) posterior repair from January 2007 to January 2018 in Fourth Medical Center, General Hospital of People's Liberation Army. The middle compartment defects were predominant in these patients with point C no less than point Ba or Bp if accompanied with anterior or posterior vaginal wall prolapse. Follow-up visits were performed 2,6 and 12 months after surgery and then annually. Anatomic results of pelvic organ prolapse (POP) was established by pelvic examination using pelvic organ prolapse quantitation system (POP-Q) staging. Funtional results were obtained by patient global impression of improvement (PGI-I) scale in POP, pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7). Surgical success required the fulfillment of all 3 criteria: (1) anterior or posterior vaginal wall prolapsed leading edge of 0 cm or less and apex of 1/2 total vaginal length or less; (2) the absence of POP symptoms as reported on the PFDI-20 question No.3 ( "Do you usually have a bulge or something falling out that you can see or feel in your vaginal area?" ); and (3) no prolapse reoperations or pessary use during the study period. Results: Of 79 women, 51(65%, 51/79) women completed the five-year follow-up during the study period. The median follow-up time was 5.2 years (2.8-8.3 years). The overall surgery success rate was 86% (44/51) according to above all 3 criteria. Prolapse recurrence rates were isolated anterior 8% (4/51), isolated apical 0, isolated posterior 2% (1/51) and multiple compartments 4% (2/51). Seven women (14%,7/51) developed anterior or posterior prolapse beyond the hymen with the leading edge≤1 cm. No apical prolapsed occurred. None of recurrent women underwent retreatment,including either surgery or pessary usage at last follow-up. The subjective satisfaction rate was 90% (46/51). There was a 1% (1/79) rate of intraoperative ureteral kinking and 3% (2/79) rate of postoperative morbidity. Conclusions: The transvaginal HUS for middle compartment defect offers good long-term anatomical results with excellent vault suspension. With additional concomitant native-tissue anterior and (or) posterior repair, it will be a reconstructive surgery for the majority of moderate-to-severe POP. It is minimal traumatic and worthy of being popularized for clinical application.

[Effectiveness of vaginal high uterosacral ligament suspension for treatment of recurrent pelvic organ prolapse].

Objective: To evaluate the indications and clinic outcomes of vaginal high uterosacral ligament suspension (HUS) for treatment of recurrent advanced pelvic organ prolapse (POP). Methods: This retrospective study analyzed 42 women with recurrent advanced POP who were referred to Fourth Medical Center of PLA General Hospital and underwent transvaginal HUS between November 2005 and January 2018. Primary surgeries included 30 vaginal colporrhaphy, 5 Manchester operation, 5 transvaginal mesh repair,2 sacrospinous ligament fixation.The median time for recurrence from primary pelvic floor repair surgery was 9 months, including 14 cases (33%, 14/42) ≤3 months (median time was 2 months) and 25 cases (67%, 28/42) longer than 3 months (median time was 18 months).The rate of recurrent prolapse in stage Ⅲ or Ⅳ was 79% (33 cases), 45% (19 cases) and 17%(7 cases) in anterior, apical and posterior compartment respectively. Results: Transvaginal high bilateral uterosacral ligaments were identified and used for successful vaginal vault suspension after vaginal hysterectomy and residual cervical resection in all 42 consecutive patients. The cases of transvaginal mesh used in anterior wall and posterior wall were 25 (60%, 25/42) and 3 (7%, 3/42) respectively. There was no major intra- and postoperative complications,such as ureter and other pelvic organ injury. The median time of follow-up was 5.3 years after transvaginal HUS. The points of pelvic organ prolapse quantification system reduced significantly and point C improved from +0.3 cm to -8.2 cm after reoperation (P<0.01). The objective cure rate were 100% (42/42) both in apex and posterior compartment,while 93% (39/42) in anterior compartment. None had reoperation or pessary usage for recurrence of prolapse. Conclusion: Transvaginal HUS with vaginal wall repair could be as a safety, cost-effective, minimal traumatic and durable procedure for recurrent POP in the most of cases.

[Clinical management of 110 cases of polypropylene mesh and sling exposure after reconstructive pelvic floor surgery].

Objective: To explore the clinical management and outcomes of polypropylene mesh and sling exposure after reconstructive pelvic surgery (RPS) . Methods: A total of 110 cases of mesh and sling exposure after RPS were analyzed, who admitted between Jan. 2002 and Oct. 2017 in First Affiliated Hospital of PLA General Hospital, in which 3 cases were referred from other hospitals. Mesh and sling exposures were identified in the outpatient clinic and categorized and managed according to International Continence Society and International Urogynecology Association (ICS-IUGA) classification about category, time and site (CTS) of mesh complication. Outpatient management included observation, topical estrogen use and mesh removal. Management in hospital included surgical removal of exposed mesh and repair of the resulting defects under the anesthesia. Seventy-four cases were managed in the outpatient setting, and 36 cases required inpatient management. Follow-up was consecutively performed from 1 month to 10 years. Objective outcome included the surgeon's assessment of the healing state of the vaginal mucosa. Subjective outcome was evaluated with patient global impression of improvement questionnaire (PGI-I) . Results: One hundred and ten patients with mesh exposure were classified according to the different RPS underwent. There were 95 cases from transvaginal mesh surgery, 5 cases from anti-stress urinary incontinence sling surgery, and 10 cases from sacrocolpopxy. The outpatient group healed at an average of (3.0±1.8) months. Of the 36 patients who required inpatient management, 21 cases healed completely at an average of 7 days after one surgery. The remaining 8 cases required either two or three times surgeries or conservative management. In the outpatient group, the PGI-I scale very much better was found in 65 cases (87.8%) and much better in 9 cases (12.2%) . In the inpatient surgery group, the scale was very much better in 30 cases (83.3%) , and much better in 6 cases (16.7%) . Conclusions: Among patients with mesh exposure after mesh-augmented RPS, 2/3 of patients with a CTS classification 1-3 could be managed in the office, and remaining 1/3 with CTS classification 4-6 need operation under anesthesia in hospital. If the mesh and sling exposure could be scientifically classified, according to the size, site and accompany symptoms, as well as pain, most of the mesh complications after explosure could be resolved. Using the pelvic floor repair and polypropylene mesh sling, the majority of the patients could get a better outcome, without affecting the effect of the original operation.

Study on molecular mechanism of MiRNA-29a in promoting proliferation and invasion of non-small-cell lung cancer by inhibiting MTSS1.

OBJECTIVE: To investigate the biological role of micro-ribonucleic acid (miR)-29a in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: 55 cases of NSCLC tissue specimens and paired normal lung tissue specimens collected in the Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from July 2012 to April 2015 were randomly included. The fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the expression levels of miR-29a and metastasis suppressor 1 (MTSS1). Pearson correlation analysis was utilized to investigate the relationship between miR-29a expression and MTSS1 expression in NSCLC tissues, and the Kaplan-Meier survival curves were constructed to analyze the association of miR-29a expression with the survival time of NSCLC patients. A54 proliferation and invasion abilities were measured by means of plate clone formation assay, and transwell assay after the miR-29a was suppressed by miRNA inhibitor. Luciferase assay was used to detect the target gene of miR-29a. RESULTS: In NSCLC tissues, the miR-29a expression level was higher than that in normal lung tissues (p<0.05), while the expression level of MTSS1 protein was remarkably lower than that in normal lung tissues (p<0.05). The median survival time of the patients was 15.1 months in high miR-29a expression group and 18.3 months in low miR-29a expression group (p<0.05). The miR-29a expression was negatively correlated with the expression level of MTSS1 protein in NSCLC tissues (r=-0.762, p<0.05). Luciferase results suggest that miR-29a binds to the promoter region of MTSS1 and inhibits its transcription level. The expression of MTSS1 protein was up-regulated notably after miR-29a knockdown by an inhibitor. It was revealed in the results of transwell assay and plate clone formation assay that the proliferative and invasive capacity of A549 cells was significantly decreased after knockdown of miR-29a. CONCLUSIONS: The transcribed miR-29a down-regulates the protein level of MTSS1, suppressor of tumor proliferation and invasion, thereby promoting the proliferative and invasive capacity of NSCLC cells. Both miR-29a and MTSS1 are expected to become potential therapeutic targets for NSCLC.