ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Aim To explore the potential mechanism of action of Codonopsis Poria in the treatment of alco-holic liver disease(ALD).Methods TCMSP and Swiss Target Prediction were used to obtain the active ingredients and targets of Codonopsis Poria;OMMI,DisGeNET and GeneCards databases were used to obtain the targets of ALD;STRING database was used to construct the PPI network;and Bioconductor soft-ware was used to analyze the enrichment of GO and KEGG pathways.Cytoscape 3.7.1 software was used to construct the drug-component-target-disease network of Codonopsis Poria for ALD treatment,and key targets were screened for molecular docking;the effects of Codonopsis Poria on ALD rats were verified by experi-ments.Results The removal of duplicate targets ob-tained 36 chemical components and 529 potential ac-tion targets.GO enrichment analysis:2 245 biological processes,74 cellular components,125 molecular functions.KEGG enrichment analysis:159 signaling pathways,mainly involving PI3K-Akt,MAPK,AGE-RAGE signaling pathways.Molecular docking showed that AKT1,MMP9 and other targets may be the key targets of Codonopsis Poria in the treatment of ALD.Experiments showed that Codonopsis Poria could im-prove the inflammation level of hepatocytes in ALD rats and reduce the levels of TC,TG,AST,ALT and GGT in ALD rats,PCR assay concluded that Codonopsis Po-ria could reduce the expression of PI3 K and AKT,and electron microscopy results showed that Codonopsis Po-ria could affect the autophagy of cells.Conclusions It is initially revealed that Codonopsis Poria may atten-uate inflammatory cell infiltration by affecting the ex-pression of AKT,TNF and MAPK,and it is hypothe-sized that Codonopsis Poria may affect autophagy through the PI3K-Akt signaling pathway,thus treating ALD,which is initially verified by PCR assay to pro-vide a basis for in-depth explanation of the molecular mechanism of Codonopsis Poria medicinal pairs in the treatment of ALD.

Objective:To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy.Methods:The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed,the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed.Results:Among 180 patients with multiple myeloma,23 cases developed herpes zoster(12.8％).The incidence of herpes zoster was 19.1％in patients with renal dysfunction and 23.5％after autologous hematopoietic stem cell transplantation(ASCT).The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens(21/137,15.3％)than that in those without bortezomib(2/43,4.7％),but there was no statistical difference(P=0.067).Antiviral prophylaxis was associated with fewer zoster infections,8/111(7.2％)developed herpes zoster in patients who received antiviral prophylaxis,and 15/69(21.7％)in those receiving no prophylaxis(P=0.005).65.2％of patients with herpes zoster did not receive antiviral prophylaxis.Multivariate analysis showed that bortezomib treatment,AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster,while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster.Herpes zoster had no effect on OS in patients with multiple myeloma.Conclusion:The risk of herpes zoster in multiple myeloma patients was increased.Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.
Cholinergic Agents/pharmacology* ; Acetylcholine/metabolism* ; Neurons/metabolism* ; Synaptic Transmission/physiology*

Objective To summarize and analyze the epidemiological and clinical characteristics of COVID-19 Omicron variant cases in makeshift hospital, and the influence of age, sex and vaccination status on the disease duration, so as to provide reference for the prevention and control of the COVID-19 epidemic. Methods The epidemiological and clinical characteristics of COVID-19 cases admitted to makeshift hospital of National Convention and Exhibition Center (Shanghai) from April 9 to May 31, 2022 were retrospectively described and analyzed, and further cohort analysis was conducted to determine the influence of age, sex and vaccination status on the disease duration of COVID-19 cases in the author's branch hospital. Results Among the 174 466 COVID-19 cases in makeshift hospital, most of them were male, accounting for 59.38%. The infected cases were mainly young and middle-aged people aged 18-59 years old, accounting for 83.50%, followed by 12.30% of the elderly group over 60 years old; the average hospital stay was 7.40 days; the proportion of patients with fever was less than 27.79%; 15.37% (26 817/174 466) of the patients complicated with underlying diseases, and the top three were hypertension, diabetes and coronary heart disease. The proportion of people who received COVID-19 vaccine accounted for 79.56% (13 799/17 956), of which the highest proportion of three doses was 44.09%. The disease duration of 17 956 COVID-19 cases in the author's branch of makeshift hospital was 10.18 (7.34, 13.05) days. The disease duration in the elderly group was the longest with 11.34 (8.35, 14.37) days, followed by 11.17 (9.07, 14.33) days in the preschool group, 10.37 (8.14, 13.34)· days in the middle-aged group, 10.07 (7.37, 12.37) days in the school-age group, and 9.34 (7.05, 12.16) days in the young group. There was significant difference in the overall distribution of disease duration among the five groups (H=550.479 P<0.01). The disease duration in each age group basically showed a V-shaped distribution. The disease duration was 10.27 (7.34, 12.57) days in males and 10.10 (7.25, 13.09) days in females, and there was no significant difference (Z=-1.505 P>0.05). The disease duration of vaccinated patients was 10.24 (7.35, 13.05) days, and that of unvaccinated patients was 9.47 (7.09, 12.47) days. There was significant difference between the two groups (Z=-4.338 P<0.01). Conclusions COVID-19 Omicron variant cases have a high proportion of males, mainly young and middle-aged, and the proportion of fever patients is less than 30%. The disease duration is significantly lower than that of the original strain in Wuhan, and shows "V" distribution with each age group. Sex had no effect on the disease duration. COVID-19 vaccination did not have a clinical effect on the disease duration.

ObjectiveTo investigate the relative content changes of differential metabolites and reducing sugars during the processing process of Rehmanniae Radix Praeparata （RRP） processed with Amomi Fructus （AF） and Citri Reticulatae Pericarpium （CRP）， and to lay the foundation for revealing the processing principle of this characteristic variety. MethodThe samples of the 0-54 h processing process of RRP processed with AF and CRP were taken as the research object， and their secondary metabolites were detected by ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The 0.1% formic acid aqueous solution （A）-acetonitrile （B） was used as the mobile phase for gradient elution （0-1 min， 1%-3%B； 1-10 min， 3%-9%B； 10-15 min， 9%-12%B； 15-22 min， 12%-18%B； 22-31 min， 18%-24%B； 31-35 min， 24%-100%B； 35-36 min， 100%-5%B； 36-40 min， 5%-1%B； 40-45 min， 1%B）， column temperature was 40 ℃， injection volume was 3 μL， flow rate was 0.3 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in the negative ion mode， the scanning range was m/z 50-1 250. Data analysis was carried out using PeakView 1.2 software， and the chemical composition of RRP processed with AF and CRP was identified by combining the literature information and chemical composition databases. The MS data were normalized by MarkerView 1.2， and then the multivariate statistical analysis was applied to screen the differential metabolites， and the changes of the relative contents of the differential metabolites with different processing times was analyzed， finally， correlation analysis was performed between the differential metabolites， the change of the reducing sugar content was combined to determine the most suitable processing time of RRP processed with AF and CRP. ResultA total of 121 compounds were identified from RRP processed with AF and CRP at different processing times， and 12 differential metabolites were screened out by multivariate statistical analysis， including catalpol， hesperidin， isoacteoside， acteoside， narirutin， echinacoside， isomartynoside， decaffeoylacteoside， 6-O-E-feruloylajugol， dihydroxy-7-O-neohesperidin， jionoside D， and rehmapicroside. With the prolongation of processing time， the relative contents of these 12 differential metabolites and reducing sugars changed slightly at 52-54 h. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents of RRP processed with AF and CRP at different processing times， and the suitable processing time of 52-54 h is determined according to the content changes of different metabolites and reducing sugars， which provides a basis for revealing the scientific connotation of the processing principle of this variety.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.