siRNA/CS-PLGA Nanoparticle System Targeting Knockdown Intestinal SOAT2 Reduced Intestinal Lipid Uptake and Alleviated Obesity.

Effective inhibition of intestinal lipid uptake is an efficient strategy for the treatment of disorders related to lipid metabolism. Sterol O-acyltransferase 2 (SOAT2) is responsible for the esterification of free cholesterol and fatty acids into cholesteryl esters. We found that intestine-specific SOAT2 knockout (Soat2I-KO) mice was capable to prevent the development of dietary induced obesity due to reduced intestinal lipid absorption. Soat2 siRNA/CS-PLGA nanoparticle system was constructed to enable intestinal delivery and inhibition of Soat2. This nanoparticle system was composed of PLGA-block-PEG and chitosan specifically delivering Soat2 siRNAs into small intestines in mice, effectively inhibit intestinal lipid uptake and resolving obesity. In revealing the underlying mechanism by which intestinal SOAT2 regulating fatty acid uptake, enhanced CD36 ubiquitination degradation was found in enterocytes upon SOAT2 inhibition. Insufficient free cholesterol esterification promoted endoplasmic reticulum stress and recruitment of E3 ligase RNF5 to activate CD36 ubiquitination in SOAT2 knockdown enterocytes. This work demonstrates a potential modulatory function of intestinal SOAT2 on lipid uptake highlighting the therapeutic effect on obesity by targeting intestinal SOAT2, exhibiting promising translational relevance in the siRNA therapeutic-based treatment for obesity.

Synthesis and Antibacterial Evaluation of Novel Psoralen Derivatives against Methicillin-Resistant Staphylococcus aureus (MRSA).

Today, the bacterial infections caused by multidrug-resistant pathogens seriously threaten human health. Thereby, there is an urgent need to discover antibacterial drugs with novel mechanism. Here, novel psoralen derivatives had been designed and synthesized by a scaffold hopping strategy. Among these targeted twenty-five compounds, compound ZM631 showed the best antibacterial activity against methicillin-resistant S. aureus (MRSA) with the low MIC of 1 µg/mL which is 2-fold more active than that of the positive drug gepotidacin. Molecular docking study revealed that compound ZM631 fitted well in the active pockets of bacterial S. aureus DNA gyrase and formed a key hydrogen bond binding with the residue ASP-1083. These findings demonstrated that the psoralen scaffold could serve as an antibacterial lead compound for further drug development against multidrug-resistant bacterial infections.

Identification of changes in bile composition in pancreaticobiliary reflux based on liquid chromatography/mass spectrometry metabolomics.

INTRODUCTION: Pancreaticobiliary reflux (PBR) can induce gallstone formation; however, its pathogenic mechanism remains unclear. In this study, we explored the mechanism of PBR by the non-targeted metabolomic analysis of bile in patients with PBR. OBJECTIVE: The aim of this study was to investigate the pathogenic mechanism in PBR by the non-targeted metabolomic analysis of bile collected during surgery. METHODS: Sixty patients who underwent gallstone surgery at our center from December 2020 to May 2021 were enrolled in the study. According to the level of bile amylase, 30 patients with increased bile amylase ( > 110 U/L) were classified into the PBR group, and the remaining 30 patients were classified into the control group (≤ 110 U/L). The metabolomic analysis of bile was performed. RESULTS: The orthogonal projections to latent structure-discriminant analysis of liquid chromatography mass spectrometry showed significant differences in bile components between the PBR and control groups, and 40 metabolites were screened by variable importance for the projection value (VIP > 1). The levels of phosphatidylcholine (PC) and PC (20:3(8Z,11Z,14Z)/14:0) decreased significantly, whereas the levels of lysoPC (16:1(9z)/0:0), lysoPC (15:0), lysoPC (16:0), palmitic acid, arachidonic acid, leucine, methionine, L-tyrosine, and phenylalanine increased. CONCLUSIONS: Significant differences in bile metabolites were observed between the PBR and control groups. Changes in amino acids and lipid metabolites may be related to stone formation and mucosal inflammation.

Effects of early aquatic exercise intervention on trunk strength and functional recovery of patients with lumbar fusion: a randomized controlled trial.

This study investigated the effectiveness of an early aquatic exercise program on trunk muscle function and functional recovery of patients with lumbar fusion. Twenty-eight subjects were divided into two equal groups. Patients in the aquatic group performed two 60-min aquatic exercise sessions and three 60-min home exercise sessions per week for 6 weeks, whereas those in the control group performed five sessions of 60-min home exercises per week for 6 weeks. The primary outcomes were the Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI), and the secondary outcomes were Timed Up and Go Test (TUGT), trunk flexor and extensor muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness measured pre- and post-intervention. Compared with participants in the control group, those in the experimental group showed significant improvement in NPRS, ODI, trunk extensor strength, lumbopelvic control, lumbar multifidus muscle thickness, and relative change in multifidus muscle thickness (significant time by group interactions, P < 0.05). Participants in both groups showed significant time effects (P < 0.001) for TUGT and trunk flexor strength outcome. Aquatic exercise combined with home exercise was superior to home exercise alone in reducing pain, disability and improving muscle strength, lumbopelvic stability, and lumbar multifidus muscle thickness.

Risk Factors for Early Recurrence of Gallstones in Patients Undergoing Laparoscopy Combined With Choledochoscopic Lithotomy: A Single-Center Prospective Study.

Objective: For patients with gallstones, laparoscopy combined with choledochoscopic lithotomy is a therapeutic surgical option for preservation rather than the removal of the gallbladder. However, postoperative recurrence of gallstones is a key concern for both patients and surgeons. This prospective study was performed to investigate the risk factors for early postoperative recurrence of gallstones. Methods: The clinical data of 466 patients were collected. Each patient was followed up for up to 2 years. The first follow-up visit occurred 4 months after the operation, and a follow-up visit was carried out every 6 months thereafter. The main goal of each visit was to confirm the presence or absence of gallbladder stones. The factors associated with gallstone recurrence were analyzed by univariate analysis and Cox regression. Results: In total, 466 eligible patients were included in the study, and 438 patients (180 men and 258 women) completed the 2-year postoperative follow-up. The follow-up rate was 94.0%. Recurrence of gallstones was detected in 5.71% (25/438) of the patients. Univariate analysis revealed five risk factors for the recurrence of gallstones. Multivariate Cox regression analysis showed that multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallbladder stones were the three predictive factors for postoperative recurrence of gallstones (P < 0.05). Conclusion: The overall 2-year recurrence rate of gallstones after the operation was 5.71%. Multiple gallstones, a gallbladder wall thickness of ≥4 mm, and a family history of gallstones were the three risk factors associated with early postoperative recurrence of gallstones.

Comparison of a new gasless method and the conventional CO2 pneumoperitoneum method in laparoendoscopic single-site cholecystectomy: a prospective randomized clinical trial.

To avoid CO2 pneumoperitoneum-associated cardiopulmonary side-effects during conventional laparoscopic surgeries, we have developed a gasless laparoscopic operation field formation (LOFF) device for laparoendoscopic single-site surgery. The aim of this study is to analyze the safety and efficacy of the LOFF device for laparoendoscopic single-site cholecystectomy and to verify its advantage of avoiding CO2 pneumoperitoneum-associated complications. In this prospective, randomized, observer-blinded clinical trial, eligible participants were randomized in a 1:1 ratio to undergo either conventional CO2 pneumoperitoneum assisted laparoendoscopic single-site cholecystectomy (LESS) or the new gasless LOFF device assisted laparoendoscopic single-site cholecystectomy (LOFF-LESS). Outcomes including intra-operative respiratory and hemodynamic parameters, operation time, conversion rate, complication rate, et al were compared between the two groups. A total of 100 patients were randomized to the LESS group [n = 50; mean (SD) age, 49.5 (13.9) years; 24 (48.0%) women] and the LOFF-LESS group [n = 50, mean (SD) age, 47.4 (13.3) years; 27 (54.0%) women]. Compared with the LOFF-LESS group, the LESS group witnessed significant fluctuations in intra-operative respiratory and hemodynamic parameters. The tracheal extubation time of the LESS group was significantly longer (P = 0.001). The gasless LOFF device is safe and feasible for simple laparoscopic cholecystectomy and has a predominance of avoiding CO2 pneumoperitoneum-associated cardiopulmonary side-effects. Trial registration number: ChiCTR2000033702.

Noble Metal-Free FeOOH/Li0.1WO3 Core-Shell Nanorods for Selective Oxidation of Methane to Methanol with Visible-NIR Light.

Hydroxyl radicals (•OH) generated in the photocatalytic process are crucial to the conversion of methane (CH4) to value-added methanol (CH3OH) at room temperature. However, utilizing noble metal-free catalysts and low-energy photons of solar light, such as visible and near-infrared light (vis-NIR), is difficult to provide more electron states to form •OH radicals. Here, we developed FeOOH/Li0.1WO3 core-shell nanorods via a two-step in/out co-modification of hexagonal tungsten oxide (h-WO3): (1) lithium ions intercalating into the hexagonal tunnels of h-WO3 to form Li0.1WO3 nanorods and (2) using FeOOH-wrapped Li0.1WO3 to obtain FeOOH/Li0.1WO3 core-shell nanorods. Introduction of lithium induces polaron transition in Li0.1WO3, enabling the absorption of vis-NIR light. Interestingly, FeOOH-based Fenton-like reaction when H2O2 is selected as an oxidant favors the generation of more •OH radicals available for CH4 oxidation to CH3OH. Meanwhile, FeOOH with FeIII as an "electron sink" highly improves the separation of photoinduced electrons and holes in Li0.1WO3. Eventually, efficient selective formation of CH4OH is achieved with remarkable generation rates up to ∼342 and ∼160 µmol g-1 at visible light (420-700 nm) and NIR light (≥800 nm), respectively. Our finding opens up new possibilities for developing noble metal-free catalysts for solar energy-driven CH4 conversion to CH3OH under ambient conditions.

The Clinical Application of a Self-developed Gasless Laparoendoscopic Operation Field Formation Device on Patients Undergoing Cholecystectomy.

BACKGROUND: We have designed a new gasless laparoscopic operation field formation (LOFF) device for cholecystectomy which was successfully tested on animal model. The goal of this study is to investigate the feasibility, safety and effectiveness of this LOFF device on patients undergoing cholecystectomy. METHODS: Patients with cholecystolithiasis or gallbladder polyps who underwent single port cholecystectomy from June 2015 to May 2016 were retrospectively reviewed. Either the LOFF-assisted laparoendoscopic single-port surgery (LESS) (LOFF-LESS) or the traditional LESS was performed. Operation time, intraoperative bleeding, postoperative hospital stay, surgical complications, incision pain score, shoulder and back pain and cosmetic satisfaction were compared. RESULTS: A total of 186 patients were included in this study, with 79 in the LOFF-LESS group and 107 in the LESS group. There was no significant difference between LOFF-LESS group and LESS group in operation field establishment time, cholecystectomy time, intraoperative bleeding, postoperative hospital stay, incision pain and cosmetic satisfaction. A lower intraoperative arterial carbon dioxide pressure was documented in the LOFF-LESS group (P<0.01). The incidence of postoperative shoulder and back pain was significantly lower in LOFF-LESS group (P<0.01). CONCLUSION: LOFF-LESS has comparable benefits of traditional LESS; it deceases incidence of pneumoperitoneum related complications as well.

High-Throughput Screening of Rat Mesenchymal Stem Cell Behavior on Gradient TiO2 Nanotubes.

The dimension of TiO2 nanotubes (TNTs) ranges from several nanometers to hundreds of nanometers. This variety raises the difficulty of screening suitable nanotube dimension for biomedical applications. Herein, we report the use of a simple one-step bipolar anodization method for fabrication of TNT gradients with diameter range from 30 to 100 nm. The gradient TNTs were successfully applied for high-throughput screening of TNT size effect on cell responses, including cell adhesion, proliferation, and differentiation. Results reveal that no significant difference in adherent cell number could be found within the range of 30-87 nm in both the presence and absence of serum proteins. On the contrary, large nanotubes (with outer diameter >87 nm) profoundly reduce cell adhesion in both the presence and absence of serum proteins, indicating TNT size could affect cell adhesion directly without the adsorbed proteins. The size effect on cell behavior becomes prominent with time that cell proliferation and differentiation decrease with increasing nanotube size. This size effect can be comprehended by protein adsorption and the formation of focal adhesion. Another two sample applications of gradient TNTs demonstrate gradient TNTs are promising for high-throughput screening.

Gallbladder Polypoid-Lesions: What Are They and How Should They be Treated? A Single-Center Experience Based on 1446 Cholecystectomy Patients.

BACKGROUND AND AIM: Gallbladder polypoid-lesions (GPs) are commonly seen on ultrasonography (USG), but several aspects of this problem are ill-defined. This study aimed to analyze clinic and pathologic characteristics of 1446 USG-detected GPs, identify predictive factors for cholesterol lesions and malignancy, and provide comments and recommendations on specific aspects of GPs. METHODS: We retrospectively analyzed clinic files of 1446 patients who underwent cholecystectomy for USG-detected GPs between 2008 and 2015 in Gallbladder Diseases Center, East Hospital of Tongji University. RESULTS: For the 1446 patients, the F: M ratio and the mean age were 1.06: 1 and 45 years, and most of them were asymptotic (80.3%) and had multiple polyps (62.5%). All the 1446 GPs were classified into three categories: cholesterol, benign non-cholesterol, and malignant lesions, with respective proportion of 87.1% (1260), 11.2% (162), and 1.7% (24). Over half of benign non-cholesterol lesions, of which most were premalignant neoplasm (adenoma), were less than 10 mm. Multiple number and the presence of lipid abnormalities were significantly more associated with cholesterol than non-cholesterol lesions, with odd ratios (OR) of 2.9 (P < 0.001) and 1.6 (P = 0.023), respectively. Age ≥50 years, present symptoms, size ≥10 mm and concurrent gallstones were independent predictive factors to discriminate malignant polyps from premalignant lesions, with ORs of 16.5 (P < 0.001), 6.3 (P = 0.013), 41.5 (P = 0.014), and 18.0 (P = 0.002), respectively. CONCLUSIONS: According to our proposed classification, the vast majority of GPs were cholesterol lesions without malignant potential and associating with metabolic diseases. We strongly recommend that risk factors of GPs be investigated by subtypes, and patients with GPs be treated with personalized and differentiated strategies.

Experimental use of a novel single-port gasless laparoendoscopic operative field formation device.

INTRODUCTION: Traditional laparaendoscopic surgery using CO2 pneumoperitoneum is associated with complications and the existing gasless laparaendoscopic surgery has shortcomings such as poor visibility in the operation field. To overcome the disadvantages of the current lifting gasless laparaendoscopic operation platforms, we developed an inflatable device for gasless laparoscopic operation field formation (LOFF) that can be internally installed and applied in practice. METHODS: We initially designed operation platforms for gasless laparaendoscopic single-port (GLESP) surgery. Subsequently, a triangular prismatic LOFF device was selected and applied successfully to GLESP cholecystectomy of five pigs. Ultimately, using pigs as a model, three surgical approaches (LOFF-assisted laparaendoscopic single-site (LOFF-LESS), LESS surgery, and traditional lifting (GLESP) were compared, and the advantages and drawbacks of inflatable devices for gasless laparoscopic operation field assessed. RESULTS: The use of the LOFF device in GLESP cholecystectomy was first evaluated. The time for surgical space formation (4.4 ± 1.2 and 4.8 ± 1.0), the operating time for gallbladder removal (25.2 ± 4.8 and 25.4 ± 2.7), and the loss of blood (9.4 ± 3.1and 9.2 ± 2.4) was similar between LESS and LOFF, respectively (Table 2). In contrast these parameters were higher in GLESP (6.6 ± 1.0, 30.3 ± 4.4 and 10.1 ± 2.0, respectively. The LOFF-LESS surgery exhibited a clearer exposure of the surgical field and shorter operating time than the GLESP surgery. LESS technology showed less postoperation pain, fast recovery, and extremely high cosmetic satisfaction. CONCLUSION: The LOFF device provides a safe, effective, and feasible operation platform that can be internally installed and inflated for GLESP surgery during cholescytectomy in animal models.

Towards scarless surgery: a novel laparoscopic cholecystectomy by using 2-mm needle-shape instruments without trocar.

OBJECTIVE: We introduce a new laparoscopic cholecystectomy by using 2-mm needle-shape instruments and compare it with single-incision laparoscopic cholecystectomy. PATIENTS AND METHODS: From January 2011 to June 2011, 60 patients who satisfied the inclusion and exclusion criteria were prospectively selected and randomized to receive either a scar-hidden novel laparoscopic cholecystectomy (NLC group) (n=30) or a single-incision laparoscopic cholecystectomy (SILC group) (n=30). Their operation time, pain score, and satisfaction score were contrasted. RESULTS: All operations were successful. Two patients were converted to conventional three-port laparoscopic cholecystectomy in the SILC group. No postoperative complications occurred in both groups. The operation time was significantly lower in the NLC group (14.17±3.51 minutes in the NLC group versus 24.67±4.12 minutes in the SILC group, P<.01). As to the satisfaction score, the NLC group was superior to the SILC group (4.53±0.57 in the NLC group versus 4.07±0.52 in the SILC group P<.01). There was also a lower postoperative pain score in the NLC group, although the results did not reach statistical significance. CONCLUSIONS: The new scar-hidden laparoscopic cholecystectomy is a safe and feasible technique. Compared with single-incision laparoscopic cholecystectomy, it has a lower operation time and less difficulty but a higher satisfaction score. It demonstrates a new approach for minimal invasive surgery.

Gas-free single-port transumbilical laparoscopic cholecystolithotomy: preliminary report on eight cases.

BACKGROUND: To explore the feasibility and safety of gas-free single-port transumbilical laparoscopic cholecystolithotomy. METHODS: An incision of 1.5-2.0 cm was made through all layers of the umbilicus, and a specially designed silicone plug with three 5-mm ports was inserted. The surgical space was created by lifting the right abdominal wall with an abdominal suspension set. A laparoscope, S-type dissector, grasper,electric needle, and needle-holder were used to perform a cholecystolithotomy. The procedure was performed in 8 patients with gall stones. RESULTS: All stones were successfully removed. No postoperative complications, such as bleeding or bile leakage, occurred. The operative time was 45-120 minutes (mean 77.5 ± 24). The mean length of hospital stay was 2 days, and no postoperartive analgesics were used. There were no visible scars on the abdominal wall. CONCLUSIONS: The gas-free single-port transumbilical laparoscopic approach was safe and feasible for cholecystolithotomy. This approach expands the applications of laparoendoscopic single-site surgery and avoids the use of highly concentrated CO(2) in the body and its potential side effects.

Optimized transumbilical endoscopic cholecystectomy: a randomized comparison of two procedures.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and transumbilical endoscopic surgery (TUES) are being developed to improve minimally invasive surgery further. In 2006, the authors developed TUES using a single triple-channel trocar or single-trocar (ST) technique. To minimize the risk and improve the surgical efficiency further, the procedure was optimized using a two-trocar (TT) technique, with both trocars in the umbilicus. This study compared the clinical results for the TT and ST techniques. METHODS: For this study, 32 patients with chronic gallbladder disease and indications for cholecystectomy were randomly assigned to undergo surgery with either the TT technique (17 patients) or the ST technique (15 patients). With the TT procedure, two modified 5-mm trocars with small handles were inserted through the navel, one above and one below the umbilicus. Another 2-mm trocar was inserted for a grasper in the right upper abdomen. With the ST procedure, one 15-mm umbilical incision was made for insertion of a previously developed triple-channel trocar to apply the laparoscope, grasper, and dissector individually. Operation time, postoperative hospital stay, and postoperative pain were compared between the two procedures. RESULTS: The mean operative time was significantly shorter with the TT technique (35.71 +/- 9.74 min) than with the ST technique (125.25 +/- 18.9 min (p < 0.001). Use of analgesics after surgery also was less in the TT group than in the ST group (0 vs. 7, respectively; p < 0.05). The postoperative hospital stay did not differ significantly between the two groups (p > 0.05). CONCLUSIONS: Although both procedures were based on the transumbilical approach, the TT approach was found to be faster and less painful than the ST approach. The difference in the cosmetic result was minimal.

Diagnosis and treatment of bacterial pneumonia in liver transplantation recipients: report of 33 cases.

BACKGROUND: Bacterial pneumonia in the recipients of liver transplantation (LTX) is a common postoperative complication influencing the prognosis greatly. In this article, the diagnosis and treatment of bacterial pneumonia in 33 LTX recipients are reported. METHODS: From February 1999 to January 2003, a total of 103 patients underwent allogeneic LTX at our center; afterwards, a retrospective analysis was made on their postoperative clinical manifestations, including symptoms (expectoration, panting and fever), sign (rale), results of laboratory examinations (white blood cell count and sputum culture of tracheal secretions or pleural fluid culture), and chest X-ray films. The following data of the pneumonia and non-pneumonia groups were collected, and the rank sum test (SPSS 11.0, Wilcoxon's method) was used to analyze the duration of postoperative respirator utilization and the volume of pleural effusion through pleurocentesis or pleural drainage. RESULTS: In the 103 patients, 33 experienced 53 episodes of bacterial pneumonia during their hospital stay after transplantation, 14 of them (42.42%) had more than three manifestations of the seven mentioned above. The pathogens causing bacterial pneumonia included Pseudomonas aeruginosa (17.48%), Klebsiella pneumoniae (15.53%), Acinetobacter baumannii (10.68%), and Staphylococcus aureus (7.77%). Amilkacin, tienam, ciprofloxacin, vancomycin, etc. were the antibiotics of choice against those bacteria. Acute rejection occurred during the treatment of bacterial pneumonia in 16 patients, and 5 of them died. Wilcoxon's rank sum test of the data indicated that the pneumonia group had longer duration of postoperative ventilator treatment and larger volume of pleural effusion than the non-pneumonia group (P < 0.05). CONCLUSIONS: The clinical manifestations of pneumonia after LTX might be atypical, and special attention should be paid to the respiratory symptoms and signs within 2 months after LTX. Whenever the diagnosis of bacterial pneumonia is confirmed, consideration should be given to reasonable use of antibiotics and regulation of immunity in addition to other routine therapies.

[Diagnosis and treatment of lung aspergillosis after liver transplantation].

OBJECTIVE: To assess the diagnosis and treatment of invasive lung aspergillosis after liver transplantation. METHODS: Routine sputum culture was performed. Itraconazole and fluconazole were used to prevent fungal infection prophylactically. Amphyotericin B was only used on aspergillosis. In 54 patients receiving, liver transplantation, 3 patients with lung aspergillosis were reviewed. RESULTS: Of the 3 patients 2 died and 1 recovered. CONCLUSIONS: Over-immunosuppression is a main risk factor for aspergillosis. Amphotericin B is still the best choice for the treatment of aspergillosis and its gradual, interrupted, low concentration administration, cooperated with itraconazole can ease the side effects.