Objective To compare the cost-effectiveness between sodium valproate and levetiracetam in the treatment of childhood epilepsy and provide an economic basis for clinical medication choices. Methods A cost-effectiveness analysis was conducted using a decision tree model to compare the effectiveness and drug costs of sodium valproate and levetiracetam in treating childhood epilepsy. Single-factor sensitivity analysis and probabilistic sensitivity analysis were used to assess the impact of parameter variations on the study results. Results The treatment cost of levetiracetam was significantly higher than that of sodium valproate. The incremental cost-effectiveness ratio （ICER） of levetiracetam compared to sodium valproate was ¥8 628.43. Sensitivity analysis results were consistent with the base-case analysis. The probabilistic sensitivity analysis showed that, over a 6-month treatment period, levetiracetam became a more cost-effective option when the willingness-to-pay （WTP） threshold was ¥9,000 or higher. One-way sensitivity analysis revealed that the price of levetiracetam was the most influential factor affecting the ICER. Conclusion When the WTP per effective pediatric epilepsy case is ¥9,000 or higher, levetiracetam demonstrates a cost-effectiveness advantage.

ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

ObjectiveTo understand the current drug resistance status and bacterial multilocus sequence typing （MLST） of human and avian Campylobacter jejuni in Jinshan District， Shanghai. MethodsFecal samples were collected from diarrhea patients in the annuity mountainous area from 2021 to 2022， and poultry and related samples were collected from 2 poultry farms in the Jinshan area for detection of C. jejuni. Minimal inhibitory concentration （MIC） drug sensitivity test was performed on the detected C. jejuni， and some strains were selected for whole genome sequencing and MLST analysis. ResultsA total of 823 samples of diarrhea disease were collected， and 32 strains of C. jejuni were detected， with a detection rate of 3.89%. Out of 600 poultry related samples， 62 strains of C. jejuni were detected， with a detection rate of 10.33%. Human multidrug resistance reached 93.75% （30/32）， while avian multidrug resistance reached 100.00%（62/62）. The top four drug resistance rates of human and avian C. jejuni were azithromycin （100.00% from humans and 100.00% from birds）， naphthoic acid （93.75% from humans and 87.10% from birds）， ciprofloxacin （90.63% from humans and 98.39% from birds）， and tetracycline （84.38% from humans and 98.39% from birds）. The relatively low resistance strains of human derived C. were erythromycin， chloramphenicol， and thalithromycin. The relatively low resistance strains of avian C. jejuni were erythromycin， clindamycin， and flufenicol. MLST analysis showed that the selected 16 strains of bacteria were divided into 9 ST types， among which the evolutionary relationship of avian C. jejuni was relatively concentrated， while human C. jejuni was relatively dispersed. It was found that one strain of avian C. jejuni was closely related to two strains of human C. jejuni. ConclusionsC. jejuni infection is severe in patients with diarrhea in this region， with a detection rate second only to salmonella and Vibrio parahaemolyticus. C. jejuni infection in poultry is relatively common， and both are highly resistant. Therefore， monitoring and control should be strengthened. MLST analysis shows new ST types in both avian and human sources of C. jejuni， indicating the emergence of new mutations that require continuous monitoring to avoid the epidemics caused by new strains. The isolated strains with close genetic relationships between avian and human sources reveal the evidence of the spread of C. jejuni from poultry to humans. Therefore it is necessary to strengthen the monitoring of C. jejuni in relevant samples from breeding farms.

ObjectiveTo determine the drug sensitivity and molecular typing characteristics of Klebsiella pneumoniae isolated from meat and diarrhea samples in a local area. MethodsSeventy-one strains of K.pneumoniae were isolated from 118 meat food （chicken and pork） randomly sampled in the markets in Jinshan District， Shanghai， 2020‒2021， and 1 499 diarrhea samples from outpatient diarrhoea patients in hospitals in the same district. Then drug susceptibility testing was conducted by micro-broth dilution method， and sequence identity was determined by pulsed field gel electrophoresis（PFGE）. ResultsThe overall detection rate of K.pneumoniae in meat was 11.86% （14/118）， with detection rate 20.93% （9/43） in chicken and 6.67% （5/75） in pork. The difference in detection between meats was statistically significant （χ²=5.317，P<0.05）. The detection rate of K.pneumoniae in diarrhea samples was 3.80% （57/1 499）. Furthermore， the isolated strains showed the highest resistance to ampicillin at 76.06%. The multi-drug resistant strains included 5 of human origin （8.77%） and 2 of foodborne origin （14.28%）. Additionally， 1 foodborne imipenem-resistant strain was detected. A total of 71 strains of K.pneumoniae were found to have 70 banding types， with similarity ranging from 39.4% to 100%， suggesting genetic diversity. ConclusionK.pneumoniae isolated from foodborne and diarrhea samples showed multi-drug resistance in Jinshan District， . with scattered PFGE banding patterns. It is recommended to strengthen the monitoring of this pathogen in the population and animal food， and be alert to the emerging multi-drug resistant strains and risk of food chain transmission.

Objective To investigate the clinical features and risk factors of primary biliary cholangitis(PBC)comorbid with metabolic associated fatty liver disease(MAFLD)and the interaction between the two diseases.Methods A total of 187 patients who were diagnosed with PBC,MAFLD,or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients,PBC+MAFLD group with 38 patients,and MAFLD group with 79 patients.Related data were collected,including general information,clinical symptoms,serological parameters,transient elastography(FibroScan),and non-invasive fibrosis markers,which were compared between the three groups.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups,the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups,and the binary Logistic regression analysis was used for multivariate analysis.Results There were significant differences between the three groups in sex,age,height,weight,body mass index(BMI),and history of autoimmune diseases(P<0.05).In the PBC+MAFLD group,female patients accounted for 89.5%,with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m2,and in the PBC group,the detection rate of autoimmune diseases was 25.7%(18 patients).There were significant differences between the three groups in the incidence rates of weakness,poor appetite,pruritus,jaundice,varices,ascites,and splenomegaly(all P<0.05).The PBC+MAFLD group had the common symptoms of weakness in 18 patients(47.4%),poor appetite in 15 patients(39.5%),abdominal pain in 14 patients(36.8%),and abdominal distension in 16 patients(42.1%);the MAFLD group had the common symptoms of abdominal pain in 34 patients(43%)and abdominal distension in 32 patients(40.5%);the PBC group had the common symptoms of weakness in 37 patients(52.9%),poor appetite in 25 patients(35.7%),jaundice in 25 patients(35.7%),abdominal pain in 18 patients(25.7%),abdominal distension in 25 patients(35.7%),varices in 19 patients(27.9%),ascites in 23 patients(32.9%),and splenomegaly in 44 patients(62.9%).The PBC+MAFLD group had a controlled attenuation parameter(CAP),which was higher than that of the PBC group,and the PBC group had significantly higher levels of liver stiffness measurement,aspartate aminotransferase-to-platelet ratio index(APRI),and fibrosis-4(FIB-4)than the MAFLD group(all P<0.05).The factors without multicollinearity were included in the regression analysis,and with the PBC group as the reference group,FIB-4(odds ratio[OR]=0.218,95%confidence interval[CI]:0.069-0.633,P<0.05)and history of autoimmune diseases(OR=0.229,95%CI:0.067-0.810,P<0.05)were influencing factors for the onset of PBC with MAFLD;with the MAFLD group as the reference group,ALT(OR=0.157,95%CI:0.025-1.000,P<0.05)and TBil(OR=0.995,95%CI:0.990-0.999,P<0.05)were influencing factors for the onset of PBC with MAFLD.Conclusion PBC with MAFLD lacks specific clinical manifestations,and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation.PBC comorbid with MAFLD may not aggravate the disease progression of PBC.