Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

This experiment was conducted to investigate the effects of agaric polysaccharides on an-tioxidant capacity,immune function,and intestinal flora of calves.Twenty-four healthy Holstein calves of(30±3)days of age and with the similar body weight at(55.33±1.86)kg were selected and randomly divided into two groups:the control group(group C)and test group(group T)with 12 replicates in each group and one calves in each replicate.Group C was fed starter and milk repla-cer,and group T was fed starter and milk replacer with 10 g of agaric polysaccharides to each calve for 10 d.Serum antioxidant,immune indexes and intestinal flora were tested.The results showed as follows:compared with group C,the enzyme activities of SOD and GSH-Px in serum of calves in group T were significantly increased(P＜0.05),and were increased by 29.09％and 15.35％,re-spectively;compared with group C,IgA,IL-2 and TNF-α were significantly increased in T group(P＜0.05).Adding agaric polysaccharides significantly increased the relative abundance of Firmi-cutes(P＜0.05)and decreased the relative abundance of Proteobacteria in feces of calf(P＞0.05);the relative abundance of Lactobalillus and Faecalibacterium were increased(P＜0.05);the relative abundance of Butyricoccus-pullicaecorum was increased(P＜0.05).LEfSe analysis results showed that there were 11 marker species in group T,such as Firmicutes and Lactobacillus,and 9 marker species in group C,such as Proteobacteria.The results showed that agaric polysaccharides could improve the antioxidant capacity and immune function of calves,and also could improve the structure of intestinal flora.

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED 50 of 18 μg. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

Objective:To develop and validate a nomogram model for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on preoperative enhanced computed tomography imaging features and clinical data.Methods:The clinical data of 210 patients with HCC undergoing surgery in the Second Affiliated Hospital of Anhui Medical University from May 2018 to May 2022 were retrospectively analyzed, including 172 males and 38 females, aged (59±10) years old. Patients were randomly divided into the training group ( n=147) and validation group ( n=63) by systematic sampling at a ratio of 7∶3. Preoperative enhanced computed tomography imaging features and clinical data of the patients were collected. Logistic regression was conducted to analyze the risk factors for HCC with MVI, and a nomogram model containing the risk factors was established and validated. The diagnostic efficacy of predicting MVI status in patients with HCC was assessed by receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) of the subjects in the training and validation groups. Results:The results of multifactorial analysis showed that alpha fetoprotein ≥400 μg/ml, intra-tumor necrosis, tumor length diameter ≥3 cm, unclear tumor border, and subfoci around the tumor were independent risk factors predicting MVI in HCC. A nomogram model was established based on the above factors, in which the area under the curve (AUC) of ROC were 0.866 (95% CI: 0.807-0.924) and 0.834 (95% CI: 0.729-0.939) in the training and validation groups, respectively. The DCA results showed that the predictive model thresholds when the net return is >0 ranging from 7% to 93% and 12% to 87% in the training and validation groups, respectively. The CIC results showed that the group of patients with predictive MVI by the nomogram model are highly matched with the group of patients with confirmed MVI. Conclusion:The nomogram model based on the imaging features and clinical data could predict the MVI in HCC patients prior to surgery.

Objective:To investigate the expression of RASAL3 in intrahepatic cholangiocarcinoma (iCCA) and the mechanism of promoting iCCA development.Methods:Tumor and paracancerous tissues were collected from 185 iCCA patients, the expression of RASAL3 was detected by immunohistochemistry, RT-qPCR and Western blot. The expression of RASAL3 and FXYD6 mRNA and protein in human cholangiocarcinoma cell line and human bile duct epithelial cells were detected with RT-qPCR and Western blot, the cell proliferation was detected with CCK-8 assay, and the activity of Na +-K +-ATPase was also detected. Results:RASAL3 was highly expressed in cholangiocarcinoma tissues and cell lines; Survival analysis showed that RASAL3 overexpression was associated with poor prognosis of cholangiocarcinoma( P<0.05) and knockdown of RASAL3 inhibits the proliferation of cholangiocarcinoma cells; Silencing RASAL3 decreases the expression of FXYD6 inhibiting the activity of Na +-K +-ATPase. Conclusion:RASAL3 is up-regulated in human cholangiocarcinoma, which can promote the occurrence and development of cholangiocarcinoma by activating FXYD6 and affecting Na +-K +-ATPase activity.

OBJECTIVE To provide reference for primary medical institutions to carry out homogeneous oncology pharmacy service . METHODS The model and procedure of homogeneous oncology pharmacy outpatient service were dujoan- established in the medical alliances . The practice data of oncology pharmacy outpatient service were retrospectively analyzed，and preliminary analysis and evaluation were conducted for the effects of pharmacy service . RESULTS During more than one year of the practice of the model ，a total of 123 patients（170 case times ）were served in the oncology pharmacy department ； 83 case times of potential drug interaction were screened for 59 patients；78 patients were intervened with adverse reactions and combined symptoms by pharmacists ，of which 65.4% of patients ’adverse reaction grades and combined symptoms improved after intervention by pharmacists ；419 case times were followed up by telephone or WeChat , including 294 case times were educated on medication；97.6% of patients understood and adopted medication education ，87.1% of patients had good medication compliance ； 55 case times （32.3%）of pharmacist intervention and medication adjustment were accepted by patients ；95.1% of the patients were very satisfied with oncology pharmacy outpatient service . CONCLUSIONS To construct a homogeneous tumor pharmacy outpatient service model in the medical alliances , can provide professional rational drug use guidance and scientific medication regulation for patients，and also can help the quality of medical alliance oncology pharmacy services to achieve homogeneous development .

Objective:To understand the epidemiological characteristics of measles outbreaks in China from 2016 to 2020 and related outbreak investigations and response performances.Methods:The information about the incidence of measles outbreaks, the investigation and response of measles outbreaks in 31 provinces from 2016 to 2020 were collected from Measles Surveillance System, and the incidence of suspected measles outbreaks detected through sporadic case finding during the same period according to the measles outbreak definition was analyzed.Results:From 2016 to 2020, a total of 344 measles outbreaks were reported nationwide, involving 1 886 measles cases. The median of intervals between the first case onsets and reported outbreaks ranged from 4 to 10 days, the median of the numbers of involved cases ranged from 2 to 3, and the median of the duration of the epidemic ranged from 8 to 13 days, and some outbreaks had long durations of 65,44,28,63 and 13 days. The top three provinces with high number of reported outbreaks were Gansu, Beijing and Shandong. Among the reported outbreaks, 115 occurred in communities/villages, accounting for the highest proportion. The genotype identification results indicated that all the outbreaks in 2016 were caused by measles virus H1, and the proportion of the outbreaks caused by measles virus H1 decreased year by year since then, which was 88.57% (31/35) in 2017, 85.00% (17/20) in 2018 and 15.79% (3/19) in 2019 respectively. There was no outbreak caused by measles H1 reported in 2020, the 4 isolates all belonged to genotype D8. Active case findings were conducted in local medical institutions for 313 outbreaks, and measles-containing vaccine coverage surveys were conducted for 266 outbreaks. From 2016 to 2020, a total of 919 suspected measles outbreaks were detected nationwide, involving 4 212 measles cases. The top three provinces with suspected measles outbreaks were Xinjiang, Gansu and Sichuan. The suspected measles outbreaks also mainly occurred in communities/villages (493).Conclusions:The number, scale and duration of measles outbreaks were gradually decreasing, the measles outbreaks at the community level can not be ignored, and the local H1 genotypes tend to be gradually replaced by other genotypes. Improving the sensitivity of outbreak surveillance, promoting vaccination, expanding the vaccine coverage, timely and effective response to the outbreaks are the focus of measles elimination in China in the future.

Methods:Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ 2 test or Fisher test. Results:No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ 2=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ 2=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ 2=4.029, P=0.045). OLH (95 % CI: 1.55 to 10.75, P=0.004) and postoperative complications (95 % CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95 % CI: 1.428 to 44.080, P=0.018) and residual stones (95 % CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95 % CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion:Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

Methods:Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ 2 test or Fisher test. Results:No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ 2=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ 2=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ 2=4.029, P=0.045). OLH (95 % CI: 1.55 to 10.75, P=0.004) and postoperative complications (95 % CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95 % CI: 1.428 to 44.080, P=0.018) and residual stones (95 % CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95 % CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion:Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.