ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

Work-related musculoskeletal disorders (WMSDs) are common and serious occupational health problems faced by primary and secondary school teachers around the world. The high prevalence of WMSD brings great harm to the physical health, psychology, daily work and life of primary and secondary school teachers. This project systematically reviewed the basic situation of WMSDs in primary and secondary school teachers at home and abroad, summarized the prevalence rate, involved body parts and main hazards of WMSDs in primary and secondary school teachers, and concluded the personal factors, occupational factors and social psychological factors leading to WMSDs. Based on this, a set of basic prevention and control measures of WMSDs were proposed from five perspectives: organizational training, organizational management, ergonomic design, individual behavior and social psychology, in order to provide a scientific basis for the prevention and treatment of WMSDs.

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (P<0.05). SBF2-AS1 knockdown resulted in decreased proliferation and invasion of Bel7402 and SK-hep1 cells (P<0.05). After miR-372-3p knockdown, the proliferation capacity and invasion number of Bel7402 cells were significantly increased. However, the above results were reversed after SBF2-AS1 knockdown (P<0.05). In addition, miR-372-3p targeted CDK6 and inhibited its expression, although over-expressing SFB2-AS1 could reverse the above results (P<0.05). Over-expressing CDK6 could reverse the inhibition of over-expressing miR-372-3p on the proliferation and invasion of Bel7402 cells. Conclusion LncRNA SBF2-AS1 can positively regulate the expression of CDK6 through miR-372-3p. It can also influence the distribution of cell cycle and affect the proliferation and invasion abilities of hepatocellular carcinoma cells.

Humans ; Dexmedetomidine/therapeutic use* ; Hypnotics and Sedatives ; Cognitive Dysfunction/drug therapy*

Objective:To explore the effective diagnosis method and the clinical effect of laparoscopic technique for atypical CE1 hepatic cystic echinococcosis.Methods:The clinical data of 17 patients with atypical liver cystic echinococcosis from June 2018 to June 2019 in the People's Hospital of Xinjiang Uygur Autonomous Region were analyzed retrospectively, including 11 males and 6 females, (46.0±21.6) years old, all patients with a history of exposure in animal husbandry area. Preoperative hydatid immunity test, abdominal ultrasound and abdominal CT examination were completed, and laparoscopic surgery was performed. Postoperative follow-up was conducted by outpatient review and telephone, and the follow-up period was up to June 2020. The diagnosis, operation and recurrence of hydatid disease by different examination methods were analyzed.Results:Preoperative serum immunological examination of 17 patients showed that 11 were positive and 6 were negative for hepatic echinococcosis. The results of abdominal CT showed that 17 cases were hepatic cyst. Conventional color doppler ultrasound showed that 14 patients were hepatic cyst, 3 patients showed cystic space occupying, and cystic hydatidosis was not excluded; 9 patients observed double track sign or local thickening of cystic wall at the top of hepatic cystic lesions after replacement of high-frequency probe, which was diagnosed as hepatic cystic echinococcosis(CE1) , 8 patients as hepatic cyst. All 17 patients underwent laparoscopic operation, during which they were definitely diagnosed as hepatic cystic echinococcosis (CE1). During the operation, there was no conversion to laparotomy. The operation time was (125.0±54.5) min, the intraoperative blood loss was (150.0±84.5) ml without blood transfusion, and the postoperative hospital stay was (6.5±2.5) d. There were no serious complications or deaths in the perioperative period, 2 cases had microbile leakage, and recovered by themselves 5-10 days after the operation; the patients were followed up for 6-12 months, no loss of follow-up, no recurrence of liver and abdominal hydatid.Conclusions:In the process of diagnosis and treatment of liver single cystic lesions, we should pay attention to the differential diagnosis of atypical CE1 hepatic cystic echinococcosis and simple liver cyst. The effective differential rate of abdominal spiral CT, hydatid immune experiment and abdominal ultrasound is low, which is easy to be misdiagnosed and missed. The high frequency probe of abdominal ultrasound can effectively find atypical CE1 hepatic cystic echinococcosis. Laparoscopic technique is not only an effective diagnosis method but also a treatment method. It is necessary to choose a reasonable operation method according to the patient's hydatidosis. Laparoscopic operation is safe and feasible in the treatment of hepatic cystic echinococcosis.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objective To explore the feasibility of Narcotrend index (NTI) for digital monitoring of light sedation depth in patients undergoing short-term mechanical ventilation after pancreaticoduodenectomy. Methods A prospective randomized controlled trial was conducted. Patients with mechanical ventilation for 12-48 hours after pancreaticoduodenectomy admitted to department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2016 to December 2018 were enrolled. They were randomly divided into two groups, and NTI and Richmond agitation-sedation score (RASS) were used to guide light sedation treatment respectively. The implementation effect of light sedation, duration of mechanical ventilation, dosage of sedative drugs, occurrence of adverse events (accidental extubation, delirium, cardiovascular events) and stress response [cortisol, epinephrine, norepinephrine, C-reactive protein (CRP)] were compared between the two groups. Results A total of 87 patients were enrolled in this study, of whom 45 received NTI-guided sedation assessment and 42 received RASS-guided sedation assessment. There were no significant differences in gender, age, body mass index (BMI), liver function classification, operation time, blood loss, conversion to laparotomy and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. During sedation treatment, the light sedation compliance rate after light sedation, 2, 4, 6 hours and cumulative compliance period number (Dt) in NTI group were higher than those in RASS group [71.1% (32/45) vs. 50.0% (21/42), 80.0% (36/45) vs. 54.8% (23/42), 88.9% (40/45) vs. 59.5% (25/42), 83.9% (642/765) vs. 62.8% (475/756), all P < 0.05]. The dosage of dexmedetomidine in NTI group was higher than that in RASS group (μg·kg-1·h-1:0.60±0.10 vs. 0.54±0.12, P < 0.01), but more patients in RASS group receiveda larger dose of propofol to maintain sedation [ratio of use of propofol: 64.3% (27/42) vs. 37.8% (17/45), dose of propofol (mg/h): 47.82±7.31 vs. 30.83±10.35, both P < 0.05]. The sedation duration and duration of mechanical ventilation in NTI group were lower than those in RASS group (hours: 15.68±2.43 vs. 17.29±2.43, 16.27±2.42 vs. 18.25±2.04, both P < 0.01). There were no significant differences in hypertension, bradycardia, accidental extubation and delirium between the two groups during sedation treatment, but the incidence of hypotension in RASS group was higher than that in NTI group [35.7% (15/42) vs. 13.3% (6/45), P < 0.05]. Compared with RASS group, epinephrine, norepinephrine and the levels of CRP at treatment of 6 hours with light sedation and 2 hours after tracheal catheter removal in NTI group were decreased [epinephrine (pg/L): 138.35±18.60 vs. 157.50±19.91, 136.24±40.40 vs. 150.46±20.22; norepinephrine (pg/L): 347.34±45.46 vs. 393.75±49.77, 340.59±50.95 vs. 376.37±49.70; CRP (μg/L): 62.26±18.78 vs. 71.31±10.32, 53.30±14.47 vs. 64.26±14.69, all P < 0.05], and cortisol level 6 hours after treatment with light sedation was lower than that of RASS group (nmol/L: 327.03±41.04 vs. 358.12±70.01, P < 0.05). Conclusion The application of NTI monitoring to guide light sedation therapy for patients with short-term mechanical ventilation after pancreaticoduodenectomy can better achieve the goal of light sedation.

Objective To investigate the clinical and molecular genetic characteristics of hypermethioninemia caused by methionine adenosyltransferase deficiency. Methods The clinical data and related gene analysis of hypermethioninemia caused by methionine adenosyltransferase deficiency in 3 children were retrospectively analyzed. The core pedigree analysis was carried out. Results Three children (2 boys and 1 girl) aged from 5 months to 3 years, were from 3 unrelated families. All of them had no family history. One case was found in neonatal screening. One case was onset with pathological jaundice at 1 month old. Another case was found due to tremor and growth retardation at 2 years old. Blood amino acid ester acyl carnitine spectrum analysis showed that all of them had significantly elevated levels of methionine at 134.50-790.67 μmol/L. All children had MAT1A mutation in methionine adenosyltransferase gene. One case was heterozygous mutations with third exon c.274T>C and seventh exon c.895C>T mutation; one case had sixth exon c.757G>A homozygous mutation; and another case had seventh exon c.791G>A homozygous mutation. The core pedigree analysis showed that the mutations were from theirs parents respectively. Conclusions For children with neurologic impairment, methionine metabolic disorders should be considered. Blood amino acids and gene analysis are important methods for confirmation of the diagnosis. Neonatal screening is an effective way to detect this disease.

Objective: To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated. Methods: Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families. Results: Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis. Conclusion Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.