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.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

The MADS-box gene family is a very important transcriptional regulator gene, which plays a role in the whole growth and development process of plants. The APETALA1 (AP1) gene is considered to play an important regulatory role in the transformation of plant flowering, but also to control the characteristic development of floral organs. Lonicera macranthoides is used as medicine with dry buds and early flowers. Therefore, studying the potential mechanism of AP1 gene in regulating flower organ development can provide a basis for improving its medicinal value by molecular means. To explore the potential mechanism of the AP1 gene in the regulation of floral organ development in L. macranthoides, the full-length cDNA of the AP1 was cloned by reverse transcription PCR (RT-PCR) and named LmMADS4. The results show that the CDS of the LmMADS4 gene is 729 bp and encodes 242 amino acids, and the LmMADS4 protein contains no signal peptide and no transmembrane structure, which is an unstable hydrophilic protein. Through homologous sequence alignment and phylogenetic analysis, LmMADS4 and L. japonica MADS27 protein cluster into one class and are closely related. Finally, the expression pattern and protein interaction pattern of LmMADS4 were analyzed by real-time reverse transcription-PCR (qRT-PCR) and yeast two-hybrid technology. The qRT-PCR showed that LmMADS4 gene was differentially expressed in the stems, leaves and flower bud at different developmental stages, including bud type variety Longhua and common variety Baiyun; and LmMADS4 gene was highly expressed in the flower buds, and with the development of flower buds, LmMADS4 gene was continuously up-regulated in the flower bud variety Longhua, however, the expression level of LmMADS4 in the Baiyun terminal flower bud was lower than that in the late flower bud, but the difference was not significant. The yeast two-hybrid results showed that the bait vector pGBKT7-LmMADS4 was not toxic to yeast strains and had no self-activating activity. LmMADS4 protein interacted with LmSVP1, LmSVP3 and LmSOC1s proteins. This study can provide a theoretical basis for exploring the mechanism of long flower bud stage and corolla non-unfolding at the molecular level and variety improvement of L. macranthoides.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

In the process of seeking new strategies to improve the efficacy of antidepressants,traditional Chinese medicine inter-vention has gradually revealed its unique prevention and treat-ment advantages.The dopamine reward system is closely in-volved in the pathological occurrence and development of depres-sion.Currently,research has mostly focused on the functional mechanism of a specific nucleus in the dopamine reward system,and there is less research focused on the functional mechanism of the neural circuit.In the current micro research on reward cir-cuits,the association between abnormal reward circuits and neg-ative emotions such as anxiety and depression has been widely recognized.Traditional Chinese medicine intervention can exert antidepressant effects by influencing reward circuits.This article provides a review on the loop mechanism of dopamine reward system involvement in depression and research on traditional Chinese medicine intervention.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.