OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

This paper summarized the experience of Professor FANG Dingya in staged treatment of Sjögren's syndrome from the perspective of dryness toxin. It is believed that the cause of Sjögren's syndrome is externally-contracted dryness， consumption of essence and fluid， congenital and acquired essence deficiency， depleted essence and insufficient blood， and the core mechanism is internal accumulation of dryness toxin. The treatment can be divided into three stages， that is dryness toxin transforming into fire-heat， damp-heat and phlegm-stasis， from the perspective of dryness metal qi transformation. It is emphasized to dispel pathogen mainly， to clear and moisten with yin-nourishing medicinals in supplementation， and to treat by stages based on syndrome differentiation. For dryness toxin with fire-heat， it is suggested to moisten dryness， resolve toxins and subdue fire， with self-made Runzao Jiedu Decoction （润燥解毒汤） in modification. For dryness toxin with damp-heat， the method of nourishing yin， clearing heat and draining dampness should be used， and Chunze Decoction （春泽汤） in modification is suggested. For dryness toxin with phlegm-stasis， it is recommended to unblock collaterals， disperse phlegm and dissipate stasis， with self-made Sanyu Xiaotan Decoction （散瘀消痰汤） in modification.

Objective:To explore the relationship between the life satisfaction of family caregivers and the de-gree of disability of disabled elderly people in Xinjiang Uygur and Kazak nationality,and the role of family mem-bers'participation in the relationship.Methods:A total of 431 elderly people with disabilities at home and their fam-ily caregivers(247 without family members and 184 with family members)were selected from Xinjiang Uygur and Kazak ethnic groups,and the survey was conducted with the Activity of Daily Living Scale(ADL)and Life Satis-faction Index B(LSIB).Results:The LSIB scores in family caregivers were negatively correlated with the ADL scores in the disabled elderly(r=-0.19,P＜0.01),and the family members'participation in care was positively correlated with the LSIB scores of family caregivers(r=0.52,P＜0.01).Family members'participation in care could moderate the negative effect of the ADL scores in the disabled elderly on the LSIB scores in family caregivers(β=0.08,P＜0.05).Conclusion:The involvement of family members in care has a moderating effect on the life satisfaction of Uyghur and Kazak family caregivers and the degree of disability of disabled elderly people.

Objective To investigate the efficacy of methylprednisolone in preventing postoperative pulmonary infections in locally advanced esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy.Methods A total of 89 patients with locally advanced esophageal cancer treated at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023 were selected as the research subjects.All patients underwent thoracolaparoscopic radical esophagectomy for esophageal cancer.The patients were randomly divided into an observation group(n=45)and a control group(n=44)using a random number table method.In the observation group,one patient with intraoperative thoracotomy,two patients with extensive pleural adhesion,and one patient with preoperative upper respiratory tract infection were excluded.In the control group,one patient with extensive pleural adhesion and one patient with preoperative upper respiratory tract infection were excluded.As a result,a total of 83 patients were included in the study,with 41 in the observation group and 42 in the control group.Preoperatively,a neoadjuvant treatment regimen of paclitaxel(albumin-bound)+nedaplatin in combination with camrelizumab was given to patients in both groups for 2 cycles.Patients in the control group received conven-tional anti-infection treatment after surgery,while patients in the observation group were intravenously injected with methylpred-nisolone at a dose of 1 mg·kg-1 daily from the first to the third day after surgery.Postoperative inflammatory markers,incidence of postoperative pulmonary infections,incidence of anastomotic fistula,postoperative hospital stay,and total hospitalization costs were compared between the two groups.Results There were no statistically significant differences in leukocyte count,neutrophil ratio,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6)levels of patients between the two groups before treatment(P＞0.05).On day 1 and 4 after treatment,patients in the observation group had significantly higher leu-kocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels compared to those before treatment(P＜0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels were significantly lower than those on day 1 postopera-tively(P＜0.05).On postoperative days 1 and 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP and IL-6 levels of patients in the control group were significantly higher than those in the preoperative period(P＜0.05),and the leukocyte count,neutro-phil ratio and hs-CRP level were significantly lower on day 4 after surgery than on day 1 after surgery(P＜0.05);the differe-nces in PCT and IL-6 level of patients between day 4 after surgery and day 1 after surgery were not statistically significant(P＞0.05).On postoperative day 1,there were no statistically significant differences in leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels between patients in the observation group and the control group(P＞0.05).On postoperative day 4,the leukocyte count,neutrophil ratio,PCT,hs-CRP,and IL-6 levels of patients in the observation group were significantly lower than those in the control group(P＜0.05).The incidence of pulmonary infections in patients in the control group and the ob-servation group was 30.9％(13/42)and 12.2％(5/41),respectively;the incidence of pulmonary infections in patients in the observation group was significantly lower than that in the control group(x2=4.298,P＜0.05).The incidence of anasto-motic fistula in patients in the observation group and the control group was 9.76％(4/42)and 21.43％(9/42),respectively;there was no statistically significant difference between the two groups(x2=2.140,P＞0.05).The postoperative hospital stay was significantly longer in the control group than in the observation group(P＜0.05),and the total hospitalization costs were significantly higher in the control group than in the observation group(P＜0.05).Conclusion Methylprednisolone can effec-tively reduce the levels of inflammatory markers and the incidence of postoperative pulmonary infections in esophageal cancer patients undergoing neoadjuvant chemotherapy combined with immunotherapy before surgery.It is a highly safe treatment thera-py without increasing the incidence of anastomotic fistula.

Objective:To isolate and identify SARS-CoV-2 epidemic strains and analyze the sequence characteristics of the virus strains following serial passages.Methods:Eleven nasopharyngeal swabs positive for SARS-CoV-2 antigen were collected from December 2022. Quantitative real-time PCR was used to detect SARS-CoV-2 nucleic acid, and positive specimens were inoculated onto Vero cells for virus isolation. The isolated strains were identified by Western blot and indirect immunofluorescence assay. The morphology of the isolated strains was observed using transmission electron microscopy. Nucleic acid was extracted from the isolates and passaged viruses for further sequencing and analysis.Results:All 11 specimens tested positive for SARS-CoV-2 using quantitative real-time PCR. SARS-CoV-2 strains were successfully isolated from seven specimens, and could be adaptively cultured, passaged, and expanded on Vero cells, achieving a peak titer exceeding 10 6.25 50% cell culture infectious dose (CCID 50)/ml. Western blot and indirect immunofluorescence results showed that the isolates could be specifically recognized by monoclonal antibodies and convalescent serum against SARS-CoV-2. Transmission electron microscopy revealed oval-shaped viral particles with diameters of approximately 100 nm. Next-generation sequencing of the viral isolates demonstrated a sequence homology greater than 99.50% with the Wuhan-Hu-1 reference strain (NC_045512) and 99.98% among the seven isolated strains, and all of the isolates belonged to the Omicron BF.7 variant. Sequence analysis after continuous passage and plaque purification of the BJ-NVSI-20230005 isolate showed that compared with passages 1-3, passages 4-6 had one nucleotide site mutation (C→T) in the ORF1ab gene and a deletion of 3 bp in the E gene, which resulted in a change from leucine to phenylalanine and the deletion of valine, respectively. Polymorphisms were observed in the sequences of plaque-purified clones. Conclusions:The seven successfully isolated SARS-CoV-2 strains all belong to the SARS-CoV-2 BF.7 variant, which is consistent with the prevalence trend in mainland China in December 2022.

Objective: To investigate the epidemiological characteristics of clusters of hand, foot and mouth disease (HFMD) in kindergartens and schools in Jinshan District, Shanghai Municipality from 2016 to 2021, so as to provide insights into improving the prevention and control measurements of HFMD in Jinshan District. Methods: Data of HFMD cases in Jinshan District from 2016 to 2021 were collected through Chinese Disease Prevention and Control Information System, and data pertaining to HFMD clusters in kindergartens and schools were also collected. The scale, temporal distribution, regional distribution and distribution of cluster places were descriptively analyzed. Results: Totally 338 HFMD clusters involving 974 cases were identified in kindergartens and schools in Jinshan District from 2016 to 2021, with an average attack rate of 9.89%. The number of cases in each cluster ranged from 2 to 12 cases, with a median number of 2 (interquartile range, 1) cases, and there were 223 clusters involving 2 cases, accounting for 65.98%. The duration of clusters ranged from 1 to 16 days, with a median duration of 4 (interquartile range, 3) days. HFMD peaked from April to June (136 clusters, 40.24%) and from September to December (176 clusters, 52.07%). All the 11 streets and towns (high-tech zones) were reported HFMD clusters, and the three largest number of clusters were reported in Zhujing Town (72 clusters, 21.30%), Shanyang Town (63 clusters, 18.64%) and Tinglin Town (40 clusters, 11.83%). There were 268 HFMD clusters in kindergartens (79.29%) and 70 in schools (20.71%), and the prevalence of HFMD clusters was higher in kindergartens than in schools (35.51% vs. 17.03%; χ2=31.507, P<0.001). Conclusions HFMD clusters in kindergartens and schools showed seasonal characteristics from 2016 to 2021 in Jinshan District, which predominantly occurred in Zhujing Town, Shanyang Town and Tinglin Town, and kindergartens were the main places.

Objective:To explore the effects of resistance training with elastic band at home on muscle function and walking ability of severely burned children.Methods:A prospective non-randomized controlled study was conducted. From January 2022 to April 2023, 40 children with severe burns who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital. According to the willingness of the children or their families, the children were assigned to conventional rehabilitation group and combined rehabilitation group. During the study, 8 children dropped out of the study, 17 children were finally included in the conventional rehabilitation group with 6 males and 11 females, aged (8.5±2.4) years, and 15 children were included in the combined rehabilitation group with 5 males and 10 females, aged (9.6±2.5) years. The children in the 2 groups received conventional burn rehabilitation treatment in the hospital, including active and passive activity training, scar massage, and pressure therapy. The children in combined rehabilitation group received resistance training with elastic band of 3 to 5 times per week after discharge, and the children in conventional rehabilitation group received daily activity ability training after discharge. Before home rehabilitation training (1 week before discharge) and 12 weeks after home rehabilitation training, the grip strength was measured using a handheld grip dynamometer, the muscle strengths of the upper and lower limbs were measured using a portable dynamometer for muscle strength, lean body mass was measured by bioelectrical impedance measuring instrument, and the 6-min walking distance was measured. Data were statistically analyzed with independent sample t test, paired sample t test, Mann-Whitney U test, or Fisher's exact probability test. Results:After 12 weeks of home rehabilitation training, the grip strengths of children in combined rehabilitation group and conventional rehabilitation group were (15±4) and (11±4) kg, respectively, which were significantly higher than (10±4) and (9±4) kg before home rehabilitation training (with t values of -9.99 and -11.89, respectively, P values all <0.05); the grip strength of children in combined rehabilitation group was significantly higher than that in conventional rehabilitation group ( t=3.24, P<0.05). After 12 weeks of home rehabilitation training, the muscle strengths of upper and lower limbs of children in combined rehabilitation group (with t values of -11.39 and -3.40, respectively, P<0.05) and the muscle strengths of upper and lower limbs of children in conventional rehabilitation group (with t values of -7.59 and -6.69, respectively, P<0.05) were significantly higher than those before home rehabilitation training, and the muscle strengths of upper and lower limbs of children in combined rehabilitation group were significantly higher than those in conventional rehabilitation group (with t values of 3.80 and 7.87, respectively, P<0.05). After 12 weeks of home rehabilitation training, the lean body mass of children in combined rehabilitation group was significantly higher than that before home rehabilitation training ( t=0.21, P<0.05). After 12 weeks of home rehabilitation training, the 6-min walking distances of children in conventional rehabilitation group and combined rehabilitation group were significantly longer than those before home rehabilitation training (with t values of -5.33 and -3.40, respectively, P<0.05), and the 6-min walking distance of children in combined rehabilitation group was significantly longer than that in conventional rehabilitation group ( t=3.81, P<0.05). Conclusions:Conventional burn rehabilitation treatment in hospital and home resistance training with elastic band for 12 weeks after discharge can significantly improve the muscle function and walking ability of severely burned children.

Objective:To systematically search and summarize the best evidence for the implementation and management of parenteral nutrition in critically ill patients.Methods:Based on the evidence-based medicine evidence structure, relevant evidence on the implementation and management of parenteral nutrition in critically ill patients was searched from top to bottom in Chinese and English databases such as China National Knowledge Infrastructure (CNKI) , VIP, British Medical Journal (BMJ) Best Practice, UpToDate and so on. The search period was from January 1, 2017 to July 31, 2022. Using the quality level of evidence and grade of recommendation system of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center in Australia, two researchers conducted literature quality evaluation and evidence summary.Results:A total of 19 articles were included, including 2 clinical decisions, 3 clinical practice guidelines, 11 expert consensuses, 2 systematic reviews, and 1 retrospective case-control study. A total of 9 themes were summarized, including the establishment of a multidisciplinary team, indications for parenteral nutrition, nutritional assessment, parenteral nutrition start time, parenteral nutrition stop time, selection and evaluation of vascular pathways, selection of infusion devices, observation of infusion processes and complications, with a total of 29 best evidences.Conclusions:The safe implementation and management of parenteral nutrition support for critically ill patients is of great significance for improving patient health outcomes. Medical and nursing staff should establish a standardized evidence-based parenteral nutrition support process to improve the safety of parenteral nutrition implementation in critically ill patients.

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.