OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Lianggesan was first recorded in Taiping Huimin Heji Jufang， which was composed of Rhei Radix et Rhizoma， Natrii Sulfas， Gardeniae Fructus， Forsythiae Fructus， Scutellariae Radix， Glycyrrhizae Radix et Rhizoma（GRR）， Menthae Haplocalycis Herba， Lophatheri Herba and Mel. It was clinically applied to treat fire-heat syndrome in the upper and middle Jiao， and the curative effect was positive. In this study， the bibliometric method was used to conduct a detailed textual research on the formula name， medicinal composition， dosage evolution， origin and processing， functional indications and other aspects of Lianggesan. Research revealed that Lianggesan has six other names， such as Lianqiao Yinzi， Lianqiao Jiedusan， Jufang Lianggesan， Jiegu Lianggesan， Hejian Lianggesan and Qingji Lianggesan. Based on the edition of Taiping Huimin Heji Jufang， an analysis of the evolution of its formula composition revealed that the missing Chinese medicines were predominantly bamboo leaves and honey， while the added Chinese medicines were primarily supplements introduced to address changes in disease manifestations. After textual research， the dosage for one dose of Lianggesan from Taiping Huimin Heji Jufang was as follows：826 g of Rhei Radix et Rhizoma， 826 g of Natrii Sulfas， 826 g of GRR， 413 g of Gardeniae Fructus， 413 g of Menthae Haplocalycis Herba， 413 g of Scutellariae Radix， and 1652 g of Forsythiae Fructus. Decocting method was as following：Grinding the Chinese medicines into coarse powder（2-4 mm）， taking 8.16 g per dose， adding 300 mL of water， along with 2 g of Lophatheri Herba and 5 g of Mel， and decocting to 140 mL. The residue was removed and taken warmly 30 min after meals. It was recommended to take it three times daily until improvement was achieved. The origins of the 9 Chinese medicines were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. Except for GRR， which required single frying（stir-frying）， the remaining medicines were all raw products. The description of the function of this formula in ancient books was summarized as purging fire and promoting bowel movements， clearing heat from the upper body and purging the lower body， and the main syndromes included facial redness， tongue swelling， red eyes， etc. In modern applications， the formula is primarily used for respiratory and digestive system diseases， including acute lung injury， chronic obstructive pulmonary disease， herpetic angina and aphthous stomatitis， covering 142 types of diseases. In summary， this paper can provide a basis for further research and development of Lianggesan through the literature review and key information combing.

Objective To investigate the safety and efficacy of selective hepatic inflow occlusion in laparoscopic hepatectomy.Methods A retrospective analysis was conducted on the clinical data of 64 patients who underwent laparoscopic hepatectomy.Based on the different methods of hepatic in-flow occlusion,the patients were divided into Pringle occlusion group with 31 patients(using inter-mittent Pringle's maneuver)and selective occlusion group with 33 patients(using selective hepatic inflow occlusion).The general,intraoperative,and postoperative data were compared between the two groups.Results There were no statistically significant differences in general data,operative time,intraoperative blood loss,central venous pressure,and mean arterial pressure between the two groups(P＞0.05).On postoperative day 3,the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBil)in the selective occlusion group were lower than those in the Pringle occlusion group(P＜0.05).There were no statistically significant differences in length of hospital stay and postoperative complication rates between the two groups(P＞0.05).Sub-group analysis showed that in patients undergoing laparoscopic hemihepatectomy,the AST and ALT levels on postoperative day 3 were lower in the selective occlusion group than in the Pringle occlusion group(P＜0.05).In patients undergoing laparoscopic liver segmentectomy,the TBil level on postop-erative day 3 was lower in the selective occlusion group than in the Pringle occlusion group(P＜0.05),but there were no statistically significant differences in AST and ALT levels between the two groups(P＞0.05).Conclusion Selective hepatic inflow occlusion demonstrates good safety and efficacy in laparoscopic hepatectomy.It can significantly reduce postoperative liver function damage,espe-cially in patients undergoing hemihepatectomy.

Objective:To explore the distribution of TCM syndromes in ulcerative colitis (UC) and their relationship with the characteristics colonoscopy mucosal and histological grading.Methods:A retrospective analysis was conducted on the TCM syndrome classification, colonoscopy mucosal images, and histological grading of 303 UC patients at Henan Provincial Traditional Chinese Medicine Hospital from January 2023 to January 2024. The characteristics and correlation of colonoscopy mucosal images and histological grading in UC patients with different TCM syndrome types was explored.Results:The top three TCM syndrome types of UC patients were large intestine damp-heat syndrome (24.75%), spleen-qi deficiency syndrome (21.12%) and liver-stagnation and spleen-deficiency syndrome (19.80%). Compared with the syndrome of spleen deficiency and dampness accumulation, heat and toxin exuberance, cold and heat mixed syndrome, liver stagnation and spleen deficiency syndrome, spleen and kidney yang deficiency syndrome, spleen qi deficiency syndrome, yin and blood deficiency syndrome, blood stasis and intestinal collateral syndrome, patients with colonic damp-heat syndrome type Ⅰ accounted for the highest proportion ( χ2=12.79, 16.24, 4.26, 16.54, 11.53, 14.16, 7.75, 10.91, P<0.05). The proportion of type Ⅲ patients was the lowest ( χ2=30.57, 33.59, 12.71, 23.63, 7.90, 19.88, 18.31, 17.31, P<0.05). Among the patients with different TCM syndrome types, the proportion of large intestine damp-heat syndrome in histological grade Ⅳ was the highest (66.67%), the proportion of blood stasis and intestinal meridian syndrome in histological grade Ⅲ was the highest (53.33%), the proportion of liver stagnation and spleen deficiency syndrome in histological grade Ⅱ was the highest (50.00%), and the proportion of spleen and kidney yang deficiency syndrome in histological grade Ⅰ was the highest (40.00%). Spearman correlation analysis showed that the large intestine damp-heat syndrome was significantly correlated with the characteristics of colonoscopy mucosal image and histological grade ( r=-0.563, 0.612, respectively, all P<0.001). The syndrome of spleen deficiency and dampness accumulation, heat and toxin exuberance, yin and blood deficiency, blood stasis and intestinal collateral were significantly positively correlated with the characteristics of colonoscopy mucosa ( r=0.373, 0.342, 0.263, 0.331, all P<0.05). The syndrome of liver stagnation and spleen deficiency and spleen and kidney yang deficiency were significantly negatively correlated with histological grade ( r=-0.417, -0.425, all P<0.01). Conclusions:The main TCM syndromes are large intestine damp-heat syndrome, spleen-qi deficiency syndrome and liver-qi deficiency syndrome, which are significantly correlated with the mucosal features and histological grade of colonoscopy. Colonoscopy and histophiologic examination can be used as objective indicators for TCM syndrome differentiation.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To explore the effect of the interaction between plasma aluminum concentration and schooling year on cognitive function, it provides the basis for early identification of its damaging effect.Methods:From October to December, 2014, 1114 on-the-job aluminum exposed workers in a large aluminum factory in Shanxi Province were investigated. The plasma aluminum concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator. The subjects were divided into low, medium, and high aluminum exposure group based on the blood lead concentration levels. The general information was collected with a self-designed questionnaire, and their cognitive function was evaluated with the mini-mental state examination and the clock drawing test. The interaction between plasma aluminum concentration level and education level was analyzed by using unconditional logistic regression fitting multiplication model and cross analysis fitting addition model.Results:The average level of plasma aluminum of the subjects was 21.68 (10.51, 45.78) μg/L. The detection rate of cognitive impairment was 19.9%. The influencing factors of cognitive function were plasma aluminum concentration, age, education level and marital status, among which high schooling year, and being married were the protective factors (all P<0.05), plasma aluminum concentration, and age were the risk factors (all P<0.05) ; After adjusting the confounding factors, such as age, marital status, schooling year, income level, smoking, and drinking, logistic regression model and the multiple linear regression model showed that there was a dose response relationship between plasma aluminum concentration and cognitive impairment. With the increase of plasma aluminum concentration, the score gradually decreased, and the risk of cognitive impairment increased ( Ptrend<0.05) ; There were multiplicative interaction ( AOR=2.15, 95% CI: 1.10-4.19) and additive interaction ( RERI=5.38, 95% CI: 2.60-8.16; AP=0.65, 95% CI: 0.51-0.80; S=3.88, 95% CI: 2.00-7.56) between plasma aluminum concentration and low schooling year on cognitive function. Conclusion:There was a dose-response relationship between aluminum exposure and cognitive impairment. There was an interaction between aluminum exposure and low schooling year. When both of them worked together, the risk of cognitive impairment increases.

X-ray is usually used to determine anatomy and localization during conventional permanent pacemaker implantation.But X-ray exposure might induce radiation injury to fetus.In this paper,we reported 2 cases successful double cavity permanent pacemaker implantation in pregnant women woman at 13 weeks of gestation under the guidance of transthoracic echocardiography.The postoperative pacing parameters were good,the whole process was finished with zero radiation,and there were complications during pregnancy.Both cases resulted in full-term pregnancies and the natural delivery of healthy newborns.Pacemaker electrodes were in normal position as confirmed by post-delivery X-ray examinations.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].