ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

Background and Aims:Laparoscopic transcystic bile duct exploration(LTCBDE)has become the preferred method for treating secondary bile duct stones due to its advantages of minimal trauma,fast recovery,and low complication rates.However,challenges remain in the dilation of the cystic duct,the insertion of the choledochoscope,and the exploration of the common hepatic duct and intrahepatic bile ducts.This study was performed to explore the clinical application and effectiveness of the programmed modified LTCBDE in the treatment of gallbladder stones combined with common bile duct stones.Methods:A retrospective analysis was conducted on the clinical data of 248 patients who underwent programmed modified LTCBDE at the Affiliated Suzhou Ninth Hospital of Soochow University from January 2018 to January 2024.The surgical strategies and treatment outcomes were summarized.Data from 913 patients who underwent laparoscopic common bile duct exploration(LCBDE)during the same period were also collected to compare surgical outcomes and postoperative complications between the two groups.Results:Through programmed surgical steps,the innovative"diaphragm"incision technique,and improved bile duct probe application,244 patients(98.4%)successfully underwent LTCBDE,while 4 patients were converted to LCBDE due to failure to insert a 4.9 mm choledochoscope through the cystic duct.After operation,1 patient(0.4%)had residual bile duct stones,which were successfully removed through T-tube tract stone extraction(this patient was converted to LCBDE during the procedure).Additionally,1 case of bile leakage and 1 case of abdominal infection(each 0.4%)occurred,both of which resolved with conservative treatment.No cases of intra-abdominal bleeding,bile duct stenosis,or bile duct injury were reported.The average operative time in the programmed modified LTCBDE group was comparable to that of the LCBDE group(85.2 min vs.88.0 min,P=0.398),but the postoperative hospital stay was significantly shorter(6.2 d vs.8.3 d,P<0.001),and the incidence of complications was lower(1.6%vs.4.7%,P=0.044).Conclusion:The programmed modified LTCBDE is a standardized,safe,and effective procedure with a low complication rate.It is worthy of further clinical promotion and application.

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

Background and Aims:Laparoscopic transcystic bile duct exploration(LTCBDE)has become the preferred method for treating secondary bile duct stones due to its advantages of minimal trauma,fast recovery,and low complication rates.However,challenges remain in the dilation of the cystic duct,the insertion of the choledochoscope,and the exploration of the common hepatic duct and intrahepatic bile ducts.This study was performed to explore the clinical application and effectiveness of the programmed modified LTCBDE in the treatment of gallbladder stones combined with common bile duct stones.Methods:A retrospective analysis was conducted on the clinical data of 248 patients who underwent programmed modified LTCBDE at the Affiliated Suzhou Ninth Hospital of Soochow University from January 2018 to January 2024.The surgical strategies and treatment outcomes were summarized.Data from 913 patients who underwent laparoscopic common bile duct exploration(LCBDE)during the same period were also collected to compare surgical outcomes and postoperative complications between the two groups.Results:Through programmed surgical steps,the innovative"diaphragm"incision technique,and improved bile duct probe application,244 patients(98.4%)successfully underwent LTCBDE,while 4 patients were converted to LCBDE due to failure to insert a 4.9 mm choledochoscope through the cystic duct.After operation,1 patient(0.4%)had residual bile duct stones,which were successfully removed through T-tube tract stone extraction(this patient was converted to LCBDE during the procedure).Additionally,1 case of bile leakage and 1 case of abdominal infection(each 0.4%)occurred,both of which resolved with conservative treatment.No cases of intra-abdominal bleeding,bile duct stenosis,or bile duct injury were reported.The average operative time in the programmed modified LTCBDE group was comparable to that of the LCBDE group(85.2 min vs.88.0 min,P=0.398),but the postoperative hospital stay was significantly shorter(6.2 d vs.8.3 d,P<0.001),and the incidence of complications was lower(1.6%vs.4.7%,P=0.044).Conclusion:The programmed modified LTCBDE is a standardized,safe,and effective procedure with a low complication rate.It is worthy of further clinical promotion and application.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Objective:To investigate the role of septum incision technique in laparoscopic transcystic common bile duct exploration (LTCBDE).Methods:The data of 22 patients with choledocholithiasis undergoing LTCBDE by septum (a membrane-like wall of the cystic duct running parallel to the common hepatic duct) incision technique at the Suzhou Ninth Hospital Affiliated to Soochow University from April 2020 to March 2023 were retrospectively analyzed, including 13 males and 9 females, aged (54.4±20.3) years. The operative time, postoperative hospital stay, postoperative complications (bile leakage, abdominal hemorrhage, abdominal infection, etc.) and follow-up data were collected and analyzed.Results:All 22 patients (including two patients undergoing common bile duct exploration through the residual cystic duct) underwent the exploration of common hepatic duct, left and right hepatic duct openings, and secondary branch openings successfully. It was confirmed using this procedure that there were no obstruction of the common hepatic duct and intrahepatic bile ducts, or residual stones. The operation time was (79.6±23.2) min and the postoperative hospital stay was (6.3±1.7) d. No complications such as biliary leakage, abdominal hemorrhage or infection occurred after surgery. No cases of biliary stricture or residual stones were observed during short-term postoperative follow-ups.Conclusion:The septum incision technique improved the visualization of hilar bile duct in LTCBDE, which could be a safe and effective procedure to facilitate the LTCBDE and increase its success rate.

There are two source plants for the traditional Chinese medicine Murrayae Folium et Cacumen (MFC) in Chinese Pharmacopoeia, i.e. Murraya exotica L. and M. paniculata (L.) Jack. Herein, a chemical comparison of M. exotica and M. paniculata by high performance liquid chromatography (HPLC) fingerprint analysis coupled with chemometrics and network pharmacology was performed. The main peaks in the fingerprints were identified by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) and authenticated by references. The chemometrics results showed that the HPLC fingerprints of these two species were clearly divided into two categories using hierarchical cluster analysis (HCA) and principal component analysis (PCA), and a total of 13 significantly differentiated markers were screened out by orthogonal partial least squares-discriminant analysis (OPLS-DA). However, the following network pharmacology analysis showed that these discriminated markers were found to act via many common targets and metabolic pathways, indicating the possibly similar pharmacological effects and mechanisms for M. exotica and M. paniculata. The above results provide valuable evidence for the equivalent use of these two plants in clinical settings. Moreover, the chromatographic fingerprint analysis coupled with chemometrics and network pharmacology supplies an efficient approach for the comparative analysis of multi-source TCMs like MFC.

Objective::To investigate the correlation between the characteristics and internal quality of Ophiopogonis Radix from Sichuan province through various quality evaluation, and provide reference for the formulation of grading standard of this herb. Method::For 28 batches of Ophiopogonis Radix, the characters, microscopic characteristics, thin-layer chromatography (TLC), the content of moisture, ash content, acid insoluble ash content, residues of sulfur dioxide, heavy metals, hazardous elements and paclobutrazol, water-soluble extract, contents of total saponins and three major components [ophiopogonin D (OPD), methylophiopogonanone A (MPOA) and methylophiopogonanone B (MPOB)] were determined.The relationships between various indicators and the grade of Ophiopogonis Radix were analyzed. Result::Ophiopogonis Radix exhibited specific properties in characters, microscopic characteristics and TLC.The contents of impurity, moisture, total ash, acid-insoluble ash and water-soluble extract existed differences in four grades of Ophiopogonis Radix from Sichuan province.For grade Ⅰ, grain number was 80-120 grains per 50 g, the moisture content was 11.1%-14.9%, total ash content was 1.6%-2.1%, acid-insoluble ash content was 0.03%-0.14%, water-soluble extract content was 77.0%-86.5%.For grade Ⅱ, grain number was 120-160 grains per 50 g, the moisture content was 13.1%-14.2%, total ash content was 1.3%-2.2%, acid-insoluble ash content was 0.06%-0.22%, water-soluble extract content was 75.9%-83.3%.For grade Ⅲ, grain number was 160-300 grains per 50 g, the impurity was 0.2%-8.4%, the moisture content was 12.6%-14.0%, total ash content was 1.2%-1.5%, acid-insoluble ash content was 0.06%-0.22%, water-soluble extract content was 74.0%-86.5%.For grade Ⅳ, grain number was 80-300 grains per 50 g, impurity was 1.2%-22.6%, the moisture content was 13.0%-15.4%, the total ash content was 1.4%-2.0%, acid-insoluble ash content was 0.03%-0.15%, water-soluble extract content was 79.8%-85.2%. Conclusion::It is reasonable and feasible to classify the grade of Ophiopogonis Radix from Sichuan province according to the appearance characteristics such as the grain number per 50 g and internal indexes such as impurity and water-soluble extract, which can be used as a reference for grading standards of Ophiopogonis Radix from Sichuan province.