Severe exercise intolerance is one of the main clinical manifestations in heart failure (HF) patients, which seriously affects patients′ quality of life. Recent studies have demonstrated that peripheral dysfunction, especially the skeletal muscle dysfunction, is a fundamental cause of exercise intolerance, rather than conventionally perceived cardiac factors. Notably, the alternation of mitochondrial function and structure dominate skeletal muscle dysfunction, and aerobic exercise is the only basic treatment for HF patients with the highest level of evidence-based medicine. This article reviews research advances on the mechanisms of skeletal muscle dysfunction and exercise intolerance in HF patients, focusing on the biogenesis, fusion, fission and autophagy of mitochondria, and further discusses the possibility of exercise training for enhancing exercise tolerance through improving mitochondrial function in HF patients.

Objective:To compare the advantages and disadvantages of laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis.Methods:From October 2020 to March 2021, 19 children with hydronephrosis were divided into two groups: intra-renal type and extra-renal type. Among them, 15 were males and 4 were females. The average age of the patients was 3.5 years old (0.2 years old to 16.8 years old), and the average weight was 18.4 kg (5.5 kg to 67.0 kg). The average ERPF of affected kidney before surgery was 35.4%(23.0%-49.8%). All of them were treated with laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty. The operation was performed in accordance with the standard surgical procedures of the guidelines. After the insertion of the trocar, the children in the transmesenteric group were exposed to the renal pelvis by incising the colonic mesangium into the retroperitoneal space, while in the retrocolic group, the peritoneum was cut into the retroperitoneal space to expose the renal pelvis. After that, the steps of incision, cutting, tube placement, and suture of the renal pelvis and ureter were the same in the two groups. Among the 10 cases of the extrarenal type, 6 cases were in the transmesenteric group and 4 cases were in the retrocolic group; among the 9 cases of the intrarenal type, 5 cases were in the transmesenteric group and 4 were in the retrocolic group. There was no statistically significant difference in age, weight, and renal function of the affected side before operation in different surgical approach groups ( P>0.05). The operation time, intraoperative anastomosis time, intraoperative blood loss and postoperative hospital stay were recorded and compared. There was no statistical difference in the age, weight, and renal function of the affected side before the operation. Results:19 cases were followed up for 6 months, no complications such as fever or wound infection occurred. The operation was successfully completed in all patients, no patients were transferred to open surgery, and the hydronephrosis was significantly reduced. Symptoms disappeared in both groups. Of the 19 children. In children with extrarenal type, the operation time of the transmesenteric group and the retrocolic group were (108.8±15.5) min and (132.8±7.6) min, and the intraoperative anastomosis time was (40.7±6.1) min and (51.5±5.5)min, the estimated intraoperative blood loss was (9.5±2.1) ml and (9.3±0.8) ml, respectively, and the postoperative hospital stay was (9.0±1.6) d and (9.3±2.9) d. The operation time and the difference of intraoperative anastomosis time was statistically significant ( P<0.05). In children with intrarenal type, the operation time of the transmesenteric group and the retrocolic group were (136.6±7.9) min and (116.5±13.5) min, and the intraoperative anastomosis time was (52.8±6.9) min and (40.8±6.2), min, the estimated blood loss during the operation was (11.4±2.3) ml and (10.5±0.9) ml, and the postoperative hospital stay was (8.8±1.7) d and (8.0±1.6) d. The operation time and The difference of intraoperative anastomosis time was statistically significant ( P<0.05). The 19 cases were followed up for 6 months, and there was no complications such as fever or wound infection. The volume of hydronephrosis was significantly reduced compared with that before operation, and the renal blood perfusion increased compared with that before operation. The difference was statistically significant ( P<0.05). Conclusion:In terms of shortening the operation time and suture time, for laparoscopic robot-assisted transmesenteric approach and retrocolic approach disconnected pyeloplasty in the treatment of children with hydronephrosis, the transtransmesenteric approach is more advantageous in the treatment of extrarenal hydronephrosis, while the retrocolic approach is more advantageous in the treatment of intrarenal hydronephrosis.

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.
Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Synthetic Biology

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

Objective Our purpose was to improve the konwlege and diagnosis level of esophageal intramural pseudodiverticulosis(EIPD).Methods All 3 cases were underwent single and double contrast esophagograms.Analyze the findings on esophagography in 3 cases.Results Multiple small tiny cyst like outpouchings with a narrow neck extending outward esophageal wall were found in all of the 3 cases, the length range of outpouchings diameter was 1-4 mm,and the length range of neck was 1-2 mm,the pseudodiverticula had a diffuse distribution in 2 cases,and segmental distribution on the middle and the lower esophagus in the other case.Some necks of pseudodiverticula incline to stomach with 30?-45? in 2 cases;and intramural tracking was found in 1 case,the length range of tracking was 5-10 mm;esophageal stenosis in esophagogastic junction and reflux esophagitis was found only in 1 case;1 case underwent endoscopy and ostiums of pseudodiverticula were found;biopsy showed submucosal chronic inflammation surrounding the neck of pseudodiverticula,squamous metaplasia of the epithelium in both the neck and outpouchings.Conclusion EIPD is a rare benign disorder characterized by dilation of the submucosal glands.The value of esophagography is to distinguish sublimes ulcer caused by esophagitis and esophageal fenestrate from EIPD.The characteristic radiographic appearance is numerous intramural esophageal contrast-filled cystiform outpouchings,and some necks incline in the direction of stomach.When the typical appearance found on barium studies,the diagnosis of EIPD can be made.