Hepatitis B virus （HBV） infection is the primary cause of viral hepatitis and represents a substantial disease burden in China. However， effective and safe agents capable of completely eliminating HBV DNA are still lacking. In modern medicine， anti-HBV strategies mainly target covalently closed circular DNA （cccDNA）， among other mechanisms， and multiple novel drugs are currently under clinical investigation. Traditional medicine has been shown to exert anti-HBV effects through direct pathways， such as blocking viral entry， as well as indirect pathways， including the regulation of programmed cell death. Studies have confirmed that the integration of traditional Chinese medicine （TCM） and Western medicine in treating HBV infection and its related complications offers complementary advantages， particularly in enhancing HBV clearance rates， improving liver function， preventing various complications， and delaying the progression from hepatic fibrosis to hepatocellular carcinoma. This review focuses on advances in anti-HBV research involving TCM， Western medicine， and their integrated application， aiming to provide a basis for integrated HBV therapy and new drug development.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To analyze the incidence rate and risk factors of atrial fibrillation (AF) in elderly patients with chronic obstructive pulmonary disease (COPD). Methods A total of 392 patients with COPD in the hospital were selected from December 2020 to December 2024. Patients' data (medical history, echocardiographic data, etc.) were recorded. The incidence rate of AF in patients was recorded and the patients were grouped according to whether or not they developed AF. The differences were compared between the two groups, and the risk factors of AF occurrence in elderly patients with COPD were analyzed. Results Among the 392 patients with COPD, 127 cases (32.40%) met the diagnostic criteria of AF. There were statistically significant differences in age, pulmonary infection, heart failure, diabetes, smoking history, disease duration, LAD, severe renal insufficiency and coronary heart disease between the AF group and the non-AF group (P<0.05). Multivariate logistic regression analysis suggested that age, pulmonary infection, heart failure, diabetes mellitus, smoking history, disease course, LAD, severe renal insufficiency and coronary heart disease were all risk factors for elderly patients with COPD (OR=1.129, 4.246, 3.955, 4.125, 2.038, 1.112, 1.102, 4.397, and 3.865, P<0.05). Conclusion The incidence rate of AF is high in elderly patients with COPD. Age, pulmonary infection, heart failure, diabetes mellitus, smoking history, course of disease, LAD, severe renal insufficiency, and coronary heart disease are all risk factors for AF.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

OBJECTIVE: To explore clinical efficacy of vancomycin-loaded antibiotic bone cement combined with induced membrane grafting for the treatment of diabetic foot ulcers(DFU). METHODS: Totally 68 DFU patients treated with bone cement combined with induced membrane grafting from November 2019 to November 2021 were retrospectively analyzed, including 37 males and 31 females, aged from 51 to 79 years old with an average of (63.63±7.85) years old;47 patients on the right side and 21 patients on the left side;28 patients with grade 2, 31 patients with were grade 3, and 9 patients with grade 4 according to Wagner's grades;the diameter of the wound ranged from 20.40 to 96.99 mm with an average of (59.67±23.26) mm. The time of wound healing, the number of operations, the survival of postoperative skin grafting, the number of postoperative recurrence and the rate of amputation were observed. RESULTS: All 68 patients were followed up for 12 to 18 months with an average of (15.06±2.12) months. The wound healing time ranged from 42 to 65 d with an average of (51.50±7.24) d, the numbers of operation ranged from 2 to 3 with an average of (2.25±0.44) times. All skin grafts were survived well after operation, without recurrence and amputation cases. CONCLUSION Vancomycin-containing antibiotic bone cement combined with induced membrane grafting is effective in treating DFU, and the operation is simple and reliable.
Humans ; Male ; Female ; Middle Aged ; Vancomycin/therapeutic use* ; Bone Cements/therapeutic use* ; Aged ; Diabetic Foot/therapy* ; Skin Transplantation ; Anti-Bacterial Agents/therapeutic use* ; Retrospective Studies ; Wound Healing/drug effects*