OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

OBJECTIVE To provide empirical basis for promoting the dynamic adjustment of the pharmaceutical care catalogue and the formulation of policies such as hierarchical payment of medical insurance. METHODS A multicenter cross- sectional survey method was adopted to conduct a questionnaire survey among 424 inpatients in 22 tertiary medical institutions in 12 prefecture-level cities of Hubei Province to evaluate their demand for pharmaceutical care， willingness to pay and preference for service forms. Combined with univariate and multivariate Logistic regression analysis， the influencing factors and key factors that affect patients’ willingness to pay for pharmaceutical care were identified. RESULTS Only 39.86% of the patients were aware of pharmaceutical care or pharmacists， and 89.62% of the patients hope to receive pharmaceutical care. Among the 16 types of pharmaceutical care， the patients surveyed had a relatively high recognition rate for guidance on drug usage and dosage， notification of medication precautions， and the identification， prevention and handling of adverse drug reactions. 96.70%， 95.30%， and 94.12% respectively expressed strong approval and approval. The demand for services such as insurance-related policy consultation， popular science on the mechanism of drug action， and assessment of the combined use of traditional Chinese and Western medicines was relatively low， with 61.65%， 68.47%， and 68.47% expressing strong approval and approval respectively. The positive influencing factors of willingness to pay were household monthly income ＞ 5 000 yuan （OR＝1.742）， awareness of pharmaceutical care or pharmacists （OR＝3.620）， and the desire to receive pharmaceutical care （OR＝4.686） （P＜0.05）， while self-rating health as “good” （OR＝0.390） was a negative influencing factor （P＜0.05）. Cardiovascular and cerebrovascular diseases （54.48%） and antihypertensive drugs （45.05%） were the service scenarios that the surveyed patients most hope to be covered. 85.14% of the patients preferred “service when xiaochnye@126.com needed”， with a single service duration of less than 10 minutes being appropriate （84.43%）， and the willingness to pay within 20 yuan being the main type （85.38%）. CONCLUSIONS Based on the characteristics of patients’ needs and payment behaviors， it is suggested that our country could consider establishing a hierarchical payment mechanism for pharmaceutical care， and focus on differentiated design in combination with diseases and medication situations. At the same time， the rights， responsibilities and service standards of resident pharmacists in the links such as medication reorganization and medical order review should be further clarified to comprehensively enhance the clinical value and policy operability of pharmaceutical care.

Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g＿Escherichia-Shigella, g＿Corynebacterium, g＿Prevotella＿9, g＿Prevotellaceae＿UCG-001, and g＿Bacteroidota＿unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals ; Rats ; Network Pharmacology ; Tandem Mass Spectrometry ; Male ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid ; Blood Glucose/drug effects* ; Rats, Sprague-Dawley ; Hypoglycemic Agents/administration & dosage* ; Poria/chemistry* ; Diabetes Mellitus, Experimental/metabolism* ; NF-kappa B/genetics* ; Gastrointestinal Microbiome/drug effects* ; Humans

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of "X-ray-free" technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 ( v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective To observe the effect of pressure-controlled ventilation volume-guaranteed(PCV-VG)mode on respiratory mechanics,lung injury markers and postoperative pulmonary complications(PPCs)in thoracoscopic patients.Methods Fifty-nine patients undergoing elective thoracoscopic lobecto-my,29 males and 30 females,aged 18-64 years,BMI 18.5-26.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using a random number table method:the PCV-VG mode group(group P,n=29)and the volume-controlled ventilation(VCV)mode group(group V,n=30).The PCV-VG mode was used for one-lung ventilation(OLV)in group P,and the VCV mode was used in group V.Anesthesia in-duction and maintenance medications were consistent in all patients.PaO2 was recorded before induction of anesthesia,5 minutes after intubation,15 minutes after OLV,30 minutes after OLV,and 3 days postopera-tively,and oxygenation index(OI)and intrapulmonary shunt rate(Qs/Qt)were calculated.Peak airway pressure(Ppeak),pulmonary dynamic compliance(Cdyn),and driving pressure(DP)were recorded 5 minutes after intubation,15 minutes after OLV,and 30 minutes after OLV.Clara cell secretory protein-16(CC-16)and interleukin-6(IL-6)concentration were measured before induction of anesthesia and after ex-tubation.Recording the occurrence of PPCs within 1 week after surgery.Results Compared with group V,Ppeak and DP were significantly reduced,Cdyn was increased significantly in group P 15 minutes and 30 minutes after OLV(P＜0.05),PaO2 and OI were significantly increased in group P 3 days postoperatively(P＜0.05),CC-16 and IL-6 concentrations were significantly reduced in group P after extubation(P＜0.05).Compared with group V,the incidence of PPCs was significantly reduced in group P(P＜0.05).Conclusion During one-lung ventilation for thoracoscopic surgery,the pressure-controlled ventilation vol-ume-guaranteed mode reduces peak airway pressure and driving pressure,improves pulmonary dynamic compliance and improves oxygenation,reduces the incidence of PPCs.

Objective To investigate the correlation between different operation timing of thoraco-scopic partial pneumonectomy and intraoperative intrapulmonary shunt rate in patients with novel coronavirus(SARS-CoV-2)infection.Methods A total of 120 patients,65 males and 55 females,aged 30-75 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,scheduled for elective thoracoscopic partial pneumo-nectomy from December 2022 to May 2023 were selected.The patients with SARS-CoV-2 infection were di-vided into three groups according to different operation timing after infection:5-8 weeks after infection(group B),9-12 weeks after infection(group C),and 13-16 weeks after infection(group D),30 pa-tients in each group.In addition,30 non-infected patients were selected as the control group(group A).Blood gas analysis was performed at 10 minutes of two-lung ventilation(TLV)and 15 and 30 minutes of one-lung ventilation(OLV)to measure radial artery and mixed venous blood gases.Intrapulmonary shunt rate(Qs/Qt)was calculated accordingly.Multiple linear regression analysis was used to investigate the cor-relation between different operation timing and intrapulmonary shunt rate in patients with SARS-CoV-2 infec-tion.The occurrence of postoperative pulmonary complications(PPCs)within 7 days after surgery was re-corded.Results Compared with group A,groups B and C exhibited significant decreases in PaO2 levels and increases in Qs/Qt ratios at 10 minutes of TLV as well as at 15 and 30 minutes of OLV(P＜0.05),group D exhibited significant decreases in PaO2 levels and increases in Qs/Qt ratios at 15 and 30 minutes of OLV(P＜0.05),group B exhibited significant increases in postoperative pulmonary infection rates and the incidence of respiratory failure within 7 days after surgery(P＜0.05).Compared with group B,the inci-dence of pulmonary infection and respiratory failure within 7 days after surgery were significantly reduced in group D(P＜0.05).Multiple linear regression analysis revealed that shorter infection time(β=-0.478,95％CI-3.857 to-1.231,P＜0.001),worsening clinical types of infection(β=0.274,95％CI 0.368 to 3.453,P=0.016),and preoperative persistent symptoms(β=-0.240,95％CI-5.986 to-0.537,P=0.019)were associated with increased intrapulmonary shunt rate at 10 minutes of TLV.Shor-ter infection time(β=0.267,95％CI 0.130 to 3.018,P=0.033),worsening clinical types of infection(β=-0.391,95％CI-4.715 to-1.323,P=0.001),preoperative persistent symptoms(β=-0.497,95％CI-10.484 to-4.491,P＜0.001),and preoperative dyspnea(β=-0.246,95％CI-8.596 to-0.691,P=0.022)were associated with increased intrapulmonary shunt rate at 15 minutes of OLV.Conclusion SARS-CoV-2 infection increases intrapulmonary shunt rate 5-8 and 9-12 weeks after infection,but the intrapulmonary shunt rate gradually recovers at 10 minutes of TLV 13-16 weeks after in-fection,and patients who undergo surgery during this interval have a lower incidence of PPCs.The shorter infection time,the aggravation of clinical classification of infection,and the presence of persistent symptoms before surgery are associated with the increase of intrapulmonary shunt rate.

ObjectiveTo explore the safety and efficacy of robot-assisted minimally invasive esophagectomy （robot-assisted minimally invasive esophagectomy， RAMIE） and thoracic laparoscopy combined with minimally invasive esophageal resection （minimal invasive esophagectomy， MIE）. MethodsThe data of 188 patients treated with Da Vinci robot assisted minimally invasive esophageal resection （RAMIE） from April 2021 to December 2022 were analyzed. In the RAMIE group， 69 patients， 49 males and 20 female， age （67.2 ± 7.2）； 119 in the MIME group， respectively， 89 males and 30 female， age （69.1 ± 7.0）. At 1 ∶ 1， including 58 patients in the RAMIE group and 58 patients in the MIE group. The t-test， Wilcoxon rank-sum test， χ² test， and so on. ResultsAfter PSM treatment， the clinical data between the two groups. There was no significant difference in operation time， postoperative tube days， and total number of lymph node dissection between the RAMIE and MIE groups （P <0.05）； the RAMIE group was better in terms of intraoperative bleeding and the MIE group， statistically significant （P <0.05）； the MIE group was better in drainage flow and lymph node dissection for three days （P <0.05）. In terms of postoperative complications， there was no statistical difference between RAMIE and MIE groups （P>0.05）. ConclusionThe recent efficacy of robot-assisted minimally invasive esophagectomy is comparable to that of thoracic laparoscopy and minimally invasive Mckeown esophagectomy； robotic-assisted minimally invasive esophagectomy can reduce intraoperative bleeding and have more advantages in left recurrent laryngeal nerve lymph node dissection.

OBJECTIVE To analyze the prevalence of potentially inappropriate medication （PIM） in elderly patients with femoral neck fractures at admission and compare the concordance of 3 evaluation criteria. METHODS A retrospective study was conducted to review the data of elderly patients with femoral neck fractures admitted to the Department of Orthopedics in Northern Jiangsu People’s Hospital from July 2022 to June 2023. The PIMs were identified according to the Criteria of Potentially Inappropriate Medications for Older Adults in China：2017 edition （hereinafter referred to as Chinese criteria）， American Geriatrics Society 2023 Updated AGS Beers Criteria® for Potentially Inappropriate Medication in Older Adults （hereinafter referred to as 2023 Beers criteria）， third version criteria for screening tool of older people’s prescriptions for potentially inappropriate medication （hereinafter referred to as STOPP criteria version 3）. The concordance of the 3 evaluation criteria was compared by using Kappa statistics. RESULTS A total of 246 patients were included in this study； 49 patients （19.92%） with 77 PIMs were detected by the Chinese criteria， 64 patients （26.02%） with 118 PIMs were detected by the 2023 Beers criteria， and 41 patients （16.67%） with 67 PIMs were detected by the STOPP criteria version 3； 22 patients met all three criteria simultaneously. The concordance among the three criteria showed moderate agreement （0.417≤Kappa≤0.486） when compared in pairs. CONCLUSIONS There are certain differences in the PIM evaluated by the three criteria， but the prevalence of PIMs is below 30% according to the different H202134） criteria. Benzodiazepines， antipsychotics， antidepressants， and other drugs may increase the risk of patients falling again.