Based on the regulation of mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway, this study investigated the effect of Jianpi Qinghua Formula on the mitochondrial fatty acid β-oxidation pathway in the livers of mice with metabolic-associated fatty liver disease(MAFLD) induced by a high-fat diet. MAFLD mice were fed a high-fat diet to establish the model, and after successful modeling, the mice were divided into the model group, the Jianpi Qinghua Formula group, and the metformin group, with an additional control group. Each group was treated with the corresponding drug or an equivalent volume of saline via gavage. Body mass and food intake were measured regularly during the experiment. At the end of the experiment, blood lipid levels and liver function-related indices were measured, liver pathological changes were observed, and protein expression levels of PGC1α, PPARα, PPARγ, and CPT1A were detected by Western blot. The results showed that, with no difference in food intake, compared to the model group, the body mass of the Jianpi Qinghua Formula group and the metformin group was reduced, liver weight and liver index decreased, and levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol(LDL-C) were lowered. Additionally, a decrease in alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was observed. Hematoxylin and eosin(HE) staining revealed reduced pathological damage to hepatocytes, while oil red O staining showed improvement in fatty infiltration. The liver disease activity score decreased, and transmission electron microscopy revealed improvement in mitochondrial swelling and restoration of internal cristae. Western blot analysis indicated that Jianpi Qinghua Formula significantly increased the expression of PGC1α, PPARα, and CPT1A proteins in the liver and reduced the expression of PPARγ. These results suggest that the Jianpi Qinghua Formula improves mitochondrial function, promotes fatty acid oxidation, and alleviates the pathological changes of MAFLD. In conclusion, Jianpi Qinghua Formula can improve MAFLD by mediating mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway.
Animals ; PPAR alpha/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Carnitine O-Palmitoyltransferase/genetics* ; Male ; Liver/metabolism* ; Fatty Liver/genetics* ; Humans ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects*

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Objective To evaluate the application efficacy of SpyGlass endoscopic direct visualization system in management of complex biliary complications after orthotopic liver transplantation. Methods Clinical data of 369 adult patients with biliary complications after orthotopic liver transplantation who received endoscopic retrograde cholangiopancreatography (ERCP) for the first time were retrospectively analyzed. Preoperative conditions, intraoperative manifestations, treatment outcomes and complications of patients treated with SpyGlass system were analyzed. Results Fifty-six patients were treated with SpyGlass system. The main preoperative symptoms included abdominal discomfort in 38 cases, fever in 8 cases, jaundice in 6 cases and skin itching in 4 cases. Ultrasound examination in 18 patients indicated common bile duct stenosis and significant intrahepatic bile duct dilatation. Preoperative magnetic resonance cholangiopancreatography (MRCP) of 56 patients revealed that 36 cases were diagnosed with common bile duct stenosis complicated with stones, 16 cases of common bile duct stenosis alone and 4 cases of suspected tumors. All patients had definite indications for SpyGlass system treatment. Among 56 patients treated with SpyGlass system, 34 cases were diagnosed with anastomotic stricture complicated with stones, 12 cases of anastomotic stricture alone, 1 case of biliary stone and 4 cases of tumors. Among 48 cases who were successfully treated, the levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, alkaline phosphatase and total bilirubin at postoperative 48 h were all significantly lower than preoperative levels (all P<0.05). No severe complications occurred in 56 patients treated with SpyGlass system. Conclusions Use of SpyGlass system may significantly increase success rate and guarantee surgical safety in the treatment of complex biliary complications after liver transplantation, which is worthy of promotion and application.

OBJECTIVE: This study tests the efficacy of Bletilla striata polysaccharide (BSP), carboxymethyl chitosan (CMC), baicalin (BA) and silver titanate (ST) in a wound dressings to fight infection, promote healing and provide superior biocompatibility. METHODS: The antibacterial activity of BA and ST was evaluated in vitro using the inhibition zone method. BA/ST/BSP/CMC porous sponge dressings were prepared and characterized. The biocompatibility of BA/ST/BSP/CMC was assessed using the cell counting kit-8 assay. The therapeutic effect of BA/ST/BSP/CMC was further investigated using the dorsal skin burn model in Sprague-Dawley rats. RESULTS: The wound dressing had good antibacterial activity against Escherichia coli and Staphylococcus aureus through BA and ST, while the combination of BSP and CMC played an important role in promoting wound healing. The BA/ST/BSP/CMC porous sponge dressings were prepared using a freeze-drying method with the concentrations of BA and ST at 20 and 0.83 mg/mL, respectively, and the optimal ratio of 5% BSP to 4% CMC was 1:3. The average porosity, water absorption and air permeability of BA/ST/BSP/CMC porous sponge dressings were measured to be 90.43%, 746.1% and 66.60%, respectively. After treatment for 3 and 7 days, the healing rates of the BA/ST/BSP/CMC group and BA/BSP/CMC group were significantly higher than those of the normal saline (NS) group and silver sulfadiazine (SSD) group (P < 0.05). Interleukin-1β expression in the BA/ST/BSP/CMC group at 1 and 3 days was significantly lower than that in the other three groups (P < 0.05). After being treated for 3 days, vascular endothelial growth factor expression in the BA/BSP/CMC group and BA/ST/BSP/CMC group was significantly higher than that in the NS group and SSD group (P < 0.05). Inspection of histological sections showed that the BA/ST/BSP/CMC group and BA/BSP/CMC group began to develop scabbing and peeling of damaged skin after 3 days of treatment, indicating accelerated healing relative to the NS group and SSD group. CONCLUSION The optimized concentration of BA/ST/BSP/CMC dressing was as follows: 6 mg BSP, 14.4 mg CMC, 0.5 mg ST and 12 mg BA. The BA/ST/BSP/CMC dressing, containing antibacterial constituents, was non-cytotoxic and effective in accelerating the healing of burn wounds, making it a promising candidate for wound healing. Please cite this article as: Gong YR, Zhang C, Xiang X, Wang ZB, Wang YQ, Su YH, Zhang HQ. Baicalin, silver titanate, Bletilla striata polysaccharide and carboxymethyl chitosan in a porous sponge dressing for burn wound healing. J Integr Med. 2023; 21(5): 487-495.
Rats ; Animals ; Chitosan/pharmacology* ; Silver/pharmacology* ; Porosity ; Vascular Endothelial Growth Factor A/pharmacology* ; Rats, Sprague-Dawley ; Wound Healing ; Polysaccharides/pharmacology* ; Bandages ; Burns/drug therapy* ; Anti-Bacterial Agents/pharmacology* ; Silver Sulfadiazine/pharmacology*

OBJECTIVE: To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8). METHODS: A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis. RESULTS: Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score. CONCLUSION The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA.
Brain/diagnostic imaging* ; Electroacupuncture ; Humans ; Magnetic Resonance Imaging/methods* ; Migraine without Aura

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

OBJECTIVES: To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis. METHODS: Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group. RESULTS: The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group. CONCLUSIONS PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.
Autoantibodies ; Glomerulonephritis, Membranous ; Humans ; Immunohistochemistry ; Receptors, Phospholipase A2 ; Thrombospondins

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.
Collagen Type III ; genetics ; Glomerular Mesangium ; Humans ; Kidney Diseases ; Kidney Glomerulus ; Proteinuria

Objective:To evaluate and compare the inpatient medical services of secondary public and private general hospitals by using disease risk adjustment model, and to explore the application of disease risk adjustment model in medical service evaluation of different ownership hospitals.Methods:Based on 1 032 865 front pages of medical records in Chengdu in 2017 and 2018, a regression model with mortality, average length of stay, total hospitalization expenses, medical service fees, drug costs and surgical consumables costs as dependent variables and related influencing factors as independent variables was established by using disease management intelligent analytic and evaluation system. The risk adjusted case mix index(ACMI) was calculated. The mortality, average length of stay, hospitalization expenses and other indicators were predicted. The ratio of observed value to expected value(O/E value) of each index in public and private secondary general hospitals was obtained and compared.Results:The ACMI value of secondary public general hospital was 4.63, slightly higher than that of private hospitals(4.55). The technical difficulty and resource consumption of the public hospitals were slightly higher than that of the private hospitals.From the O/E value, the management of disease mortality, medical service fees and inpatient drug costs of secondary public hospitals was generally good, and the O/E values of hospitalization expenses of each secondary private general hospital were quite different, and there was a possibility that the costs were unreasonable. The O/E value of surgical consumables cost in secondary public general hospital was 1.54, and there was room for improvement in cost management.Conclusions:The disease risk adjustment model fully considers the characteristics of different types and severity of diseases in different institutions, which can not be simply compared. Based on individual cases, it realizes the comparability of different ownership hospitals, and provides a new means for the evaluation of medical service ability and quality.