TBC1D15 deficiency protects against doxorubicin cardiotoxicity via inhibiting DNA-PKcs cytosolic retention and DNA damage

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15CKO) or Tbc1d15 knockin (Tbc1d15CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca2+ homeostasis in a murine model of HFpEF / 医学前沿

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca2+ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca2+ overload and fragmentation, and promoted intracellular Ca2+ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca2+ overload.

Clinical and endoscopic characteristics of adult celiac disease / 中华内科杂志

Objective:The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment.Methods:In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People′s Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed.Results:A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant ( P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD ( P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions:Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

Efficacy of video-assisted thoracoscopic surgery for pulmonary echinococcosis: A meta analysis / 中华地方病学杂志

Objective:To evaluate the efficacy and safety of video-assisted thoracoscopic surgery (VATS) and thoracotomy in the treatment of pulmonary echinococcosis.Methods:Pubmed, ScienceDirect, Medline, Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CNKI) and VIP Chinese Journal Service Platform were searched by computer from the earliest publication time of the documents included in the database to August 2020. Comparative studies on VATS and thoracotomy in the treatment of pulmonary echinococcosis were included and the quality was evaluated. The data were combined and analyzed by RevMan 5.3 software.Results:Eleven articles were finally included, including two randomized controlled trials (RCT) articles, and the rest were case-control studies. A total of 878 patients were included, including 447 in VATS group and 431 in thoracotomy group. The results of meta analysis showed that compared with thoracotomy group, VATS operation time [ MD (95% CI): - 28.59 (- 41.79, - 15.39)], intraoperative blood loss [ MD (95% CI): - 35.83 (- 49.65, - 22.01)], postoperative drainage volume [ MD (95% CI): - 94.83 (- 150.55, - 39.01)], postoperative catheterization time [ MD (95% CI): - 2.26 ( - 2.94, - 1.59)], hospital stay [ MD (95% CI): - 4.59 (- 6.51, - 2.67)], and postoperative complications [ MD (95% CI): 0.48 (0.32, 0.73)] in VATS group were significantly lower ( P < 0.05). There was no significant difference in postoperative recurrence between VATS group and thoracotomy group [ MD (95% CI): 0.75 (0.26, 2.16), P > 0.05]. Conclusions:Compared with thoracotomy, VATS in the treatment of pulmonary echinococcosis has the advantages of shorter operation time, less intraoperative blood loss, less postoperative drainage volume, shorter postoperative catheterization time and fewer postoperative complications. VATS is a safe and effective surgical method for the treatment of pulmonary echinococcosis.

Research process on pathogenesis of gastroesophageal reflux disease / 中国医师杂志

Gastroesophageal reflux disease (GERD) is a gastrointestinal motility disorder that results from the reflux of stomach contents into the esophagus or oral cavity, causing symptoms or complications. The typical symptoms of GERD are heartburn and regurgitation of gastric contents into the oropharynx. Heartburn is the sensation of burning or discomfort behind the sternum. Heartburn may radiate into the neck, is typically worse after meals or when in a reclining position, and may be eased by antacids. Regurgitation is the backflow of gastric contents into the mouth or hypopharynx. Epigastric pain can also be a symptom of GERD. Extraesophageal symptoms of GERD include dental erosions, laryngitis, cough, and asthma. In recent years, great progress has been made in understanding the molecular basis of GERD, suggesting that its pathogenesis is more complex and multifactorial. In this paper, the molecular pathogenesis was taken as the starting point, including the mechanism of genes in the pathogenesis and development of GERD, the mechanism of NF-κB pathway in the pathogenesis and development of GERD, the role of proteinase-activated receptor-2 in the pathogenesis of GERD, the association between abnormal serotonin pathway and GERD, and the relationship between reactive oxygen species and GERD, to summarize the pathogenesis of gastroesophageal reflux disease.

Research progress on the role of intestinal flora in the pathogenesis of gastroesophageal reflux disease / 中国医师杂志

Gastroesophageal reflux disease (GERD) is a global digestive system disease caused by the reflux of gastric contents into the esophagus and the injury of esophageal mucosa. At present, the pathogenesis of GERD is not completely clear. Studies have found that GERD is closely related to intestinal flora disorder and small intestine bacterial overgrowth (SIBO). Changes in intestinal flora can participate in the occurrence and development of GERD by activating immune and inflammatory reactions, affecting gastroesophageal motility and other mechanisms. In addition, intestinal flora can also indirectly regulate and affect the pathogenesis of GERD by causing some metabolic diseases. This paper aims to review the relationship between GERD and intestinal flora.

Current status and problems of human resources of centers for disease control and prevention in Kashgar District， Xinjiang Uygur Autonomous Region / 上海预防医学

ObjectiveTo evaluate the current situation of human resource allocation in district and county centers for disease control and prevention （CDCs） in Kashgar ， identify existing problems and influencing factors， and to provide scientific evidence for optimizing the human resource allocation. MethodsA survey was conducted among all CDCs in Kashgar in February 2022. The questionnaire included the institutional and individual questions. ResultsThe overall staff size approved for the CDCs in Kashgar was 604， with a staffing rate of 76.17%， among which the staffing rates in 5 county CDCs were less than 60%. Currently， there were a total of 524 approved staff members in all CDCs， resulting in a vacancy rate of 13.25%. In the district CDC， 85 staff members were on duty， while the median of staff on duty was 34 in each county CDC. The staff in the district CDC was ageing， of which those aged over 45 accounted for 67.06%. The staff in the county CDCs was generally young， of which those aged less than 35 accounted for 54.22%. Moreover， the proportion of staff with bachelor’s degree or above in the district and county CDCs was 31.76% and 24.95%， respectively. The proportion of staff without professional title was 32.94% and 48.03%， respectively. In contrast， the proportion of those with middle and senior professional title was 57.89% and 22.02%， respectively. In addition， in recent 3 years， 24 staff members resigned in the CDCs， all of whom had professional titles. ConclusionHuman resources are insufficient in CDCs in Kashgar. Furthermore， staff structure is unreasonable， with a serious loss of human resources. In particular， the district CDC needs to optimize the allocation of human resources.

Epidemiological analysis of registered tuberculosis cases in Kashgar District， Xinjiang Uygur Autonomous Region from 2011 to 2020 / 上海预防医学

ObjectiveTo determine the current status and characteristics of tuberculosis （TB） registration and treatment in Kashgar， and to provide scientific evidence for targeted prevention and control measures in future. MethodsKashgar registered TB cases information in 2011 to 2020 was exported from the National Tuberculosis Management Information System. Descriptive epidemiological analysis was conducted using Stata 12.0. ResultsFrom 2011 to 2020， number of Kashgar registered TB patients showed rising trend， followed by a falling one. Average proportion of annual decline in registered TB incidence was 40.48% from 2018 to 2020. From 2011 to 2016， number of registered TB patients in women was always higher than that in men， with a gender ratio （male ： female） of about 0.90. In 2017， the gender ratio was 1.00. From 2018 to 2020， the gender ratios were 1.05， 1.20， and 1.12， respectively. Moreover， number of registered TB cases increased with age （χ2=547.79， P<0.001）. Proportion of registered TB cases was relatively large in Shache County （16.43%‒23.64%）， Yengisar County （9.51%‒13.87%） ， Kashgar City （8.11%‒11.40%）， Yecheng County （6.98%‒13.40%） and Bachu County（4.92%‒16.65%）. Proportion of recurrent TB cases in Kashgar had increased to 27.29%， 20.77% and 28.39% in 2018， 2019 and 2020， respectively. Multivariate analysis showed that age， drug resistance， calendar year and etiological diagnosis were significantly correlated with the proportion of recurrent cases （all P<0.05）. ConclusionSince 2018， TB incidence has decreased significantly due to the increasing efforts for identification and treatment of TB cases. However， Kashgar remains facing a high TB incidence. TB cases that are elderly， drug-resistant and positive for pathogen are susceptible to recurrent treatment. In future， targeted prevention and control measures should be improved for these groups.

Review and prospect of anti-reflux surgery for gastroesophageal reflux disease in China / 中华消化外科杂志

Gastroesophageal reflux disease and its complications are harmful to human health. In recent years, due to the rising living standards and the changing diet structure of Chinese people, the incidence rate of gastroesophageal reflux disease in China is on the rise, and the awareness of clinicians on these diseases gradually increased. Laparoscopic anti-reflux surgery has become the main surgical method for the treatment of gastroesophageal reflux disease, and its curative effect has been widely recognized. At present, laparoscopic anti-reflux surgery for gastro-esophageal reflux disease has been carried out for more than 10 years in China, which has accumulated valuable experience and achieved rapid development, providing Chinese evidences for the academic community. Anti-reflux surgery for gastroesophageal reflux disease in China is also facing challenges and opportunities. How to promote anti-reflux surgery comprehensively, train professional clinicians, and improve the surgical efficacy is an important research topic of anti-reflux surgery in China. Based on the literatures at home and abroad and team experience, the authors reviewe the development of gastroesophageal reflux disease anti-reflux surgery in China, and look forward to the future development direction.

Effects of FGB gene polymorphism on fibrinogen level and gallstones incidence in Xinjiang, China / 临床肝胆病杂志

Objective To investigate the association of the polymorphisms of the FGB gene rs4220 and rs1044291 loci with plasma fibrinogen (Fg) level and gallstones in Xinjiang, China. Methods Blood samples were collected from 150 Uygur and Han patients with gallstones and 150 Uygur and Han individuals without gallstones who were hospitalized or underwent physical examination in The People's Hospital of Xinjiang Uygur Autonomous Region from December 2017 to May 2020. Plasma Fg level was measured, and based on the previous results of whole exon sequencing of the FGB gene, the SNaPshot method was used to identify the genotype at rs4220 and rs1044291 loci of the FGB gene. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the association between each variable and gallstones. Results For the Chinese Han population, the gallstones group had a significantly higher plasma Fg level than the control group [2.90 (2.43-3.49) g/L vs 2.47 (2.06-3.02) g/L, Z =-3.62, P 0.05). For the Chinese Han population, the subjects carrying GG genotype at the rs4220 locus in the gallstones group had a significantly higher plasma Fg level than those in the control group [2.84(2.32-3.61) g/L vs 2.34(2.05-2.75) g/L, Z =-3.04, P 0.05). Conclusion The influence of FGB gene polymorphism on plasma Fg level may be associated with race, and FGB gene polymorphisms at the rs4220 and rs1044291 loci may be involved in the pathogenesis of gallstones by regulating Fg level in the population in Xinjiang.

Characterization of the Onychomatricodermis Containing Onychofibroblasts of the Nail Unit :Histology, Immunohistochemistry, and Electron Microscopic Study

Background@#We recently discovered the presence of specialized nail mesenchyme below the nail matrix and designated it as onychomatricodermis. @*Objective@#We did further research to characterize the histologic, histochemical, immunohistochemical and ultrastructural features of the onychomatricodermis containing onychofibroblasts in the nail unit. @*Methods@#Ten polydactyly nail unit specimens and 8 nail matrix biopsies were included. H&E-stained slides were reviewed. We did Alcian blue staining and Masson Trichrome staining, as well as immunohistochemical staining for type Ⅰ collagen, CD10, CD13 and CD34. In addition, polydactyly nail units were examined by transmission electron microscopy. @*Results@#In H&E staining, the specialized mesenchyme called onychomatricodermis was observed to be slightly distant from the undersurface of the nail matrix and be less eosinophilic area. Onychomatricodermal onychofibroblasts showed light purple abundant cytoplasm.Masson Trichrome staining revealed fewer collagen fibers within the onychomatricodermis. In Alcian blue staining the onychomatricodermis showed mucin deposition within the onychofibroblasts and around them. Immunohistochemically, type Ⅰ collagen was expressed much less in the onychomatricodermis while it was strongly expressed elsewhere in the nail unit. In nail matrix biopsy specimens onychomatricodermal onychofibroblasts expressed CD10 and CD13 strongly, and expressed CD34 as well. Ultrastructurally, collagen fibrils were found sparsely within the onychomatricodermis, whereas collagen fibrils were densely distributed in the dermis of other parts of the nail unit. @*Conclusion@#We demonstrated that there was less collagen expression in the onychomatricodermis containing onychofibroblasts. In addition, we found morphological and immunohistochemical features of onychomatricodermal onychofibroblasts (onychofibroblasts of Dongyoun). These findings support the presence of onychomatricodermis containing onychofibroblasts in the nail unit.

Application of exhaled gas analysis in the diagnosis of clinical diseases / 中国医师杂志

There are more than 3 000 kinds of volatile organic compounds (VOCs) in human exhaled gas, which are directly or indirectly related to the pathophysiological process of the body. Therefore, the detection and quantitative analysis of VOCs in vivo is helpful for the early detection, diagnosis and evaluation of treatment results. Breath analysis is a simple, noninvasive, painless, economic and time-saving detection method. It is a new field of rapid development, and has great potential in disease screening and clinical diagnosis. In this paper, the application of human exhaled gas analysis in clinical disease diagnosis and the latest progress in this field will be summarized.

Positioning error analysis of intensity modulated radiation therapy after modified radical mastectomy for breast cancer patients with modified head neck and shoulder thermoplastics mask / 中华放射医学与防护杂志

Objective:To analyze the difference of positioning accuracy by cone beam CT(CBCT) between modified head neck shoulder thermoplastic mask and breast bracket in intensity modulated radiotherapy for breast cancer patients after modified radical mastectomy.Methods:A total of 68 cases of breast cancer treated with IMRT after modified radical mastectomy were selected from August 2015 to December 2018. According to the different immobalization methods, the patients were divided into two groups: modified head neck shoulder thermoplastic mask group (body mask group, 42 cases) and breast bracket group (bracket group, 26 cases). After the first, sixth, 11th, 16th and 21st treatment, the patients were scanned by CBCT. The positioning errors in left and right (RL), anterior and posterior (AP) and head and foot (SI) directions were obtained, and the duration of radiotherapy positioning was recorded. The positioning error, distribution ratio and positioning duration were compared between two groups, and the respective MPTV margin were calculated. The influence of various factors on the setup error of patients was analyzed in the mask group. Results:There were 210 scans in the body mask group and 130 in the bracket group. The setup errors of the body mask group and bracket group in RL, AP and SI directions were (2.12±2.01) and (2.38±1.92) mm, (3.29±2.46) and (3.88±2.76) mm, (3.47±2.29) and (4.11±3.15) mm, respectively, and the differences in AP and SI directions were statistically significant ( t=-2.05, -2.16, P<0.05). The proportion of setup errors less than or equal to 3 mm in the direction for body mask group was higher than that of bracket group ( χ2=4.97, P<0.05). The proportion of setup errors more than 5 mm in AP and SI directions for body mask group was lower than that of bracket group ( χ2=5.21, 9.29, P<0.05). The positioning duration of mask group was shorter than of bracket group ( t=-2.16, P<0.05). The MPTV margins of the mask group in RL, AP and SI directions were smaller than those of the bracket group. The modified head, neck and shoulder thermoplastic mask immobalization method led to large setup errors in AP and / or SI directions for the elderly (≥ 60 years old), the patients with body mass index (BMI) ≥ 24 kg/m 2 and the patients who were relatively unfamiliar with the radiotherapy process (treatment time≤ 2 weeks). The setup error for patients aged < 60 years old in SI direction was smaller than that for the elderly (≥ 60 years old) patients ( t=-2.43, P<0.05). The setup error for patients with BMI <24 kg/m 2 in AP and Si directions was smaller than that with BMI ≥24 kg/m 2 ( t=-2.21, -2.04, P<0.05). The setup error for treatment time > 2 weeks in AP direction was smaller than that for treatment time ≤ 2 weeks ( t=2.23, P<0.05). Conclusions:In IMRT radiotherapy for breast cancer patients after modified radical mastectomy, the application of modified head neck shoulder thermoplastic mask can reduce the setup error in the anterior-posterior and superior-inferior directions, and shorten the positioning duration. For the elderly (≥ 60 years old), BMI ≥ 24 kg/m 2 and the patients who are not familiar with the radiotherapy process (treatment time ≤ 2 weeks), attention should be paid to the setup of anterior-posterior and superior-inferior directions to ensure the treatment effect of radiotherapy.

The expression of NADPH oxidase-4 and acid sensitive receptors in the esophagus of chronic restraint mice / 中国医师杂志

Objective:To investigate the chronic restraint stress induced expressions of acid sensitive receptors and its role in the esophageal inflammation and oxidative stress.Methods:Twenty male specific pathogen free (SPF) Kunming mice were randomly divided into two groups: stress group and control group (each group, n=10). Stress mice were restrained in self-made restraint device for 2 hours per day and lasted for total 14 days. The histopathological changes of esophageal mucosa were observed by hematoxylin eosin (HE) staining under light microscope. The expression of nicotinamide adenine dinucleotide phosphate (Nox-4) was detected by immunohistochemistry, real time fluorescent quantitative polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA). The mRNA expressions of acid sensitive receptors were detected by qRT-PCR. Results:HE staining showed that stress mice had obvious infiltrations of neutrophils and eosinophils, and also showed inflammatory change in esophgus, while no significant abnormality was found in the esophagus of control mice. The inflammotory scores in stress group were significantly higher than that in control group ( P<0.001). Immunohistochemistry showed that Nox-4 was mainly expressed in the lamina propria, mucosa and submucosa of esophagus. The mRNA expression levels of Nox-4 in stress group was (2.67±0.62) times higher than control group, with statistically significant difference ( P<0.001). In addition, the plasma concentration of Nox-4 in stress group was significantly higher than that of control group [(0.42±0.01)ng/ml vs (2.13±0.35)ng/ml, P<0.001]. The transcription levels of acid sensitive receptors in stressed mice, such as transient receptor potential vanilloid-1 (TRPV-1), TRPV-4, acid-sensing ion channel-1 (ASIC-1), ASIC-2 and ASIC-3 were significantly higher than those in the control group, with statistically significant difference ( P<0.001). Pearson correlation analysis showed that there was a positive correlation between Nox-4 mRNA expression and TRPV-1, TRPV-4, ASIC-1, ASIC-2, ASIC-3 mRNA expression in stress group ( r=0.97, 0.94, 0.98, 0.95 and 0.99, P<0.01). Conclusions:Stress may increases the expression of acid sensitive receptors and result in an esophageal inflammation and oxidative stress, which may contribute to the formation of esophageal hypersensitivity.

Clinical efficacy of laparoscopic sleeve gastrectomy for obesity complicated with obstructive sleep apnea syndrome / 中华消化外科杂志

Objective:To investigate the clinical efficacy of laparoscopic sleeve gastrectomy (LSG) for obesity complicated with obstructive sleep apnea syndrome (OSAS).Methods:The retrospective and descriptive study was conducted. The clinical data of 74 patients with obesity complicated with OSAS who were admitted to People's Hospital of Xinjiang Uygur Autonomous Region from January 2017 to June 2018 were collected. There were 40 males and 34 females, aged (39±10)years, with a range from 20 to 56 years. Observation indicators: (1) surgical and postoperative situations; (2) follow-up; (3) correlation analysis between obesity indicators and OSAS indicators; (4) analysis of factors influencing the postoperative efficacy of OSAS. Follow-up using hospitalization examination was conducted to detect the incidence of complications and the improvement of obesity and OSAS indicators after patients discharge. The follow-up was up to June 2019. Measurement 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 or percentages. Repeated measurement data was analyzed using the mixed-effects model. Correlation analysis was conducted using the Pearson correlation coefficients. Multivariate analysis was conducted using the COX proportional risk regression model. Results:(1) Surgical and postoperative situations: 74 patients underwent LSG successfully, without conversion to open surgery, including 12 cases undergoing LSG combined with laparoscopic cholecystectomy and 9 cases undergoing LSG combined with esophageal hiatal hernia repair. The operation time and volume of intraoperative blood loss of 74 patients were (88±22)minutes and (57±25)mL. There was no severe postoperative complications and perioperative mortality. The duration of postoperative hospital stay of 74 patients were 5 days (range, 3-8 days). (2) Follow-up: among 74 patients, 71 were followed up at 1 month, 68 were followed up at 3 months, 64 were followed up at 6 months and 61 were followed up at 12 months after operation, respectively. The body mass, body mass index (BMI), abdominal circumference, chest circumference, neck circumference, apnea hypopnea index (AHI), average oxyhemoglobin saturation (ASaO 2), lowest oxygen saturation, epworth sleepiness scale score, excess weight loss rate of the 71 patients who were followed up at 1 month after operation were (108±16)kg, (38±5)kg/m 2, (121±14)cm, (122±13)cm, (41.3±2.5)cm, (25±15)times/hour, 88.1%±3.8%, 70.0%±9.3%, 17.8±2.3, 30%±8%, respectively. The above indicators of the 68 patients who were followed up at 3 month after operation were (96±14)kg, (33±5)kg/m 2, (113±13)cm, (120±12)cm, (39.7±2.3)cm, (17±11)times/hour, 90.2%±3.1%, 78.5%±7.1%, 15.0±2.2, 52%±13%, respectively. The above indicators of the 64 patients who were followed up at 6 month after operation were (88±11)kg, (31±4)kg/m 2, (105±11)cm, (113±11)cm, (37.5±1.7)cm, (10±7)times/hour, 92.4%±2.2%, 84.2%±3.5%, 13.6±1.7, 63%±14%, respectively. The above indicators of the 61 patients who were followed up at 12 month after operation were (80±8)kg, (28±3)kg/m 2, (97±8)cm, (108±10)cm, (36.5±1.4)cm, (6±4)times/hour, 93.7%±1.4%, 88.0%±3.1%, 9.2±1.5, 75%±16%, respectively. There were significant differences in the body mass, BMI, abdominal circumference, chest circumference, neck circumference, AHI, ASaO 2, lowest oxygen saturation, epworth sleepiness scale score of patients before and after operation ( F=109.855, 108.632, 90.565, 27.846, 96.353, 49.969, 48.561, 115.938, 257.762, P<0.05). There were 39 cases with AHI<5 times/hour in the 61 patients who were followed up at 12 month after operation, and the clinical complete response rate of OSAS was 63.93%(39/61). (3) Correlation analysis between obesity indicators and OSAS indicators: results of the Pearson correlation analysis showed that the AHI was positively correlated with the body mass and BMI ( r=0.267, 0.317, P<0.05) and negatively correlated with the ASaO 2 and lowest oxygen saturation ( r=-0.525, -0.551, P<0.05), and there was no correlation between AHI and neck circumference ( P>0.05) in the 74 patients before operation. The lowest oxygen saturation was negatively correlated with the body mass and BMI ( r=-0.330, -0.400, P<0.05), and there was no correlation between lowest oxygen saturation and neck circumference ( P>0.05) in the 74 patients before operation. The AHI was negatively correlated with the ASaO 2 and lowest oxygen saturation ( r=-0.406, -0.373, P<0.05), and there was no correlation between AHI and the body mass, BMI or neck circumference ( P>0.05) in the 61 patients who were followed up at 12 month after operation. There was no correlation between lowest oxygen saturation and the body mass, BMI or neck circumference ( P>0.05) in the 61 patients who were followed up at 12 month after operation. (4) Analysis of factors influencing the postoperative efficacy of OSAS: results of the multivariate analysis showed that preoperative AHI was an independent influence factor for postoperative efficacy of OSAS ( hazard ratio=1.039, 95% confidence interval: 1.016-1.063, P<0.05). Conclusion:LSG can effectively reduce the body mass and improve OSAS of patients with obesity complicated with OSAS in the short term.

The role of Nox-4 in gastric mucosal inflammation induced by chronic restraint stress in mice / 中华行为医学与脑科学杂志

Objective To investigate the expression of NADPH oxidase Nox-4 induced by stress in gastric mucosa and its role in inflammation.Methods Twenty male SPF Kunming mice were randomly divided into chronic restraint stress group(stress group) and control group.Stress mice were restrained in selfmade restraint device for 2 hours each day.The rest of the time,the mice in the two groups had free access to food and water normally,experiment lasted 14 days.The histopathological changes of gastric mucosa were assessed by HE staining under light microscope.The expression of Nox-4 in gastric mucosa of mice was carried out by immunohistochemical method.The relative expression levels of Nox-4,antioxidant protein (Mn-SOD,GSH,Catalase) and inflammatory factors(IL-8,IL-1β,TNF-α) in gastric mucosa were detected by real-time quantitative RT-PCR and ELISA.Results Basal cell proliferation,neutrophil,eosinophil and plasma cell infiltration and inflammatory changes were observed in the lamina propria and glandular epithelium of stress mice,while no obvious abnormalities were found in control mice.The expression of Nox-4 in stress group was deeper and more abundant than that in control group,mainly expressed in lamina propria and glandular epithelium.The mRNA expression levels of Nox-4 in gastric mucosa of stress group was(2.42±0.51) times higher than that of control group,and blood concentration of stress group was(2.23±0.67) times higher than that of control group(t=-46.32,P＜0.001).The RT-PCR of antioxidant proteins in gastric mucosa showed that the transcription levels of Mn SOD,GSH and Catalase in stress group were significantly lower than that of control group (Mn-SOD:0.59± 0.10,GSH:0.58± 0.11,Catalase:0.57± 0.09),and there were significant differences between the two groups(t=13.57,11.67,15.01,P＜0.01).RT-PCR results showed that the transcription levels of IL-8,IL-1β,TNF-α in stress group were significantly higher than those in control group (IL-8:1.47±0.34,IL-1β:1.48 ± 0.42,TNF-α:1.51 ± 0.37),and there were significant differences in two groups(t=-18.45,-19.14,-20.85,P＜0.01).ELISA results showed that the serum levels of inflammatory factors in stress group were significantly higher than those in control group(2.25±0.37,3.59±0.45,3.41±0.34),and the differences were statistically significant(t=-47.11,-79.36,-96.32,P＜0.01).Pearson correlation analysis showed that there was a positive correlation between serum concentration of Nox-4 and inflammatory factors(IL-8,IL-1β,TNF-αt) in stress group(r=0.97,0.99,0.98,P＜0.01).Spearman rank correlation analysis showed that the grade of gastric mucosal inflammation was positively correted with serum levels of Nox-4 and inflammatory factors (IL-8,IL-1β,TNF-α) (r =0.96,0.92,0.91,0.94,all P＜ 0.01)Conclusion Stress may lead to gastric mucosal lesion by overexpression of proinflammatory factors through destroying the balance of oxidation/antioxidant system in gastric mucosa.

Mechanism of YAP1-JUN promoting proliferation and EMT transformation of human laryngeal squamous cell carcinoma cells / 中国医师杂志

Objective@#To investigate the role of Yes-associated protein 1 (YAP1)-JUN in promoting the proliferation and epithelial mesenchymal transitions (EMT) transformation of laryngeal squamous cell carcinoma.@*Methods@#The expression and subcellular localization of YAP1 were detected by tissue immunofluorescence assay. The effects of YAP1 on the proliferation of laryngeal squamous cell were examined by cell clone formation experiment. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the effect of YAP1 on the expression and transcriptional level of EMT-related molecular markers. The interaction between YAP1 and JUN was detected by immunocoprecipitation (CoIP) and Western blot assay, which regulated the expression of downstream genes to control the EMT process.@*Results@#The expression of YAP1 in laryngeal squamous cell carcinoma tissue increased and transferred from cytoplasm to nucleus. The number of clones increased significantly after YAP1 up regulation (P<0.01). The expression level of key gene E-cadherin in epithelial cells was significantly inhibited after YAP1 up (P<0.01), while the expression level of the key genes of interstitial cells, β-catenin, vimentin and N-cadherin was significantly up (P<0.01). YAP1 was interacted with nuclear transcription factor JUN, and the proliferation ability of YAP1 decreased significantly (P<0.01) after the inhibition of JUN expression (P<0.01), and the expression of EMT related molecular markers decreased significantly (P<0.01).@*Conclusions@#YAP1 combined with JUN gene promotes the proliferation and EMT transformation of human laryngeal squamous cell carcinoma cells.

Mechanism of YAP1-JUN promoting proliferation and EMT transformation of human laryngeal squamous cell carcinoma cells / 中国医师杂志

Objective To investigate the role of Yes-associated protein 1 (YAP1)-JUN in promoting the proliferation and epithelial mesenchymal transitions (EMT) transformation of laryngeal squamous cell carcinoma.Methods The expression and subcellular localization of YAP1 were detected by tissue immunofluorescence assay.The effects of YAP1 on the proliferation of laryngeal squamous cell were examined by cell clone formation experiment.Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the effect of YAP1 on the expression and transcriptional level of EMT-related molecular markers.The interaction between YAP1 and JUN was detected by immunocoprecipitation (CoIP) and Western blot assay,which regulated the expression of downstream genes to control the EMT process.Results The expression of YAP1 in laryngeal squamous cell carcinoma tissue increased and transferred from cytoplasm to nucleus.The number of clones increased significantly after YAP1 up regulation (P ＜0.01).The expression level of key gene E-cadherin in epithelial cells was significantly inhibited after YAP1 up (P ＜0.01),while the expression level of the key genes of interstitial cells,β-catenin,vimentin and N-cadherin was significantly up (P ＜ 0.01).YAP1 was interacted with nuclear transcription factor JUN,and the proliferation ability of YAP1 decreased significantly (P ＜0.01) after the inhibition of JUN expression (P ＜ 0.01),and the expression of EMT related molecular markers decreased significantly (P ＜0.01).Conclusions YAP1 combined with JUN gene promotes the proliferation and EMT transformation of human laryngeal squamous cell carcinoma cells.

Analysis of 4 children with pancreatic solid pseudopapillary neoplasm treated by total laparoscopic pancreaticoduodenectomy / 中华胰腺病杂志

Objective To investigate the application and surgical experience of total laparoscopic pancreaticoduodenectomy ( TLPD ) in treating children with solid pseudopapillary neoplasm ( SPN ) of pancreas. Methods Clinical data 4 children with SPN who underwent TLPD in Jilin University First Hospital from April 2017 to June 2018 were retrospectively analyzed. Results Among the 4 children, a case was male and 3 cases were female. Their age ranged from 9 to 14 year-old, the height ranged from 1. 2 to 1. 7 meters, and body weight ranged from 30 to75 kg. All patients complained of upper abdominal pain, one child had nausea and vomiting, and one child had abdominal mass. All patients underwent abdominal enhanced CT scan before operation, which showed a mass-like low-density shadow or mixed density shadow in the pancreatic head, with slightly uneven enhancement or no obvious enhancement. All 4 patients underwent TLPD, and the operation was successful without conversion to open surgery. The duration of operation time ranged from 250 to 365 minutes, the intraoperative blood loss ranged from 80 to 120 ml, the tumor size ranged from 4 to 8 cm, and the hospital stay ranged from 10 to 22 days. One patient developed grade B pancreatic fistula after surgery and was cured after conservative treatment. Pathological examinations of all patients confirmed the diagnosis of pancreatic SPN. All patients were followed up until February 2019, and no significant discomfort was observed and no recurrence or metastasis was found. Conclusions TLPD was safe and feasible in children in relatively large pancreatic surgery centers with extensive laparotomy and TLPD experience.

Analysis of 4 children with pancreatic solid pseudopapillary neoplasm treated by total laparoscopic pancreaticoduodenectomy / 中华胰腺病杂志

Objective@#To investigate the application and surgical experience of total laparoscopic pancreaticoduodenectomy (TLPD) in treating children with solid pseudopapillary neoplasm (SPN) of pancreas.@*Methods@#Clinical data 4 children with SPN who underwent TLPD in Jilin University First Hospital from April 2017 to June 2018 were retrospectively analyzed.@*Results@#Among the 4 children, a case was male and 3 cases were female. Their age ranged from 9 to 14 year-old, the height ranged from 1.2 to 1.7 meters, and body weight ranged from 30 to75 kg. All patients complained of upper abdominal pain, one child had nausea and vomiting, and one child had abdominal mass. All patients underwent abdominal enhanced CT scan before operation, which showed a mass-like low-density shadow or mixed density shadow in the pancreatic head, with slightly uneven enhancement or no obvious enhancement. All 4 patients underwent TLPD, and the operation was successful without conversion to open surgery. The duration of operation time ranged from 250 to 365 minutes, the intraoperative blood loss ranged from 80 to 120 ml, the tumor size ranged from 4 to 8 cm, and the hospital stay ranged from 10 to 22 days. One patient developed grade B pancreatic fistula after surgery and was cured after conservative treatment. Pathological examinations of all patients confirmed the diagnosis of pancreatic SPN. All patients were followed up until February 2019, and no significant discomfort was observed and no recurrence or metastasis was found.@*Conclusions@#TLPD was safe and feasible in children in relatively large pancreatic surgery centers with extensive laparotomy and TLPD experience.