1.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
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.
2.Study on the correlation between hyperopia reserve and ocular biometric parameters after ciliary muscle paralysis in 4-14 year-old students from Hotan County, Xinjiang
Ning LI ; Yan WANG ; Lei YANG ; Qian PU ; AYINU·NULAHOU ; Xiaolong LI ; Yong ZHAO ; Yunxian GAO
International Eye Science 2025;25(8):1371-1376
AIM: To explore the relationship between hyperopia reserve and ocular biometric parameters in 4-14 year-old Uyghur students from Hotan County, Xinjiang, and to provide scientific evidence for myopia prevention.METHODS: From September 1 to October 31, 2023, a stratified random cluster sampling method was used to select 3 264 students(3 264 eyes)from 6 schools in Hotan County. Participants underwent uncorrected distance visual acuity testing, cycloplegic refraction, and ocular biometric measurements. The correlation between spherical equivalent(SE)and ocular biometric parameters was analyzed by multiple linear regression.RESULTS: A total of 1 998 non-myopic students(1 998 eyes)were included in the study, with 1 354 students(67.77%)showing insufficient hyperopia reserve. The detection rate of insufficient hyperopia reserve decreased with age, from 94.12% at age 4 to 18.13% at age 14(P<0.001). Multiple linear regression analysis showed that in the group with sufficient hyperopia reserve, age, gender, uncorrected distance visual acuity, axial length(AL), and keratometry(K)explained 66.5% of the variance in SE; while in the group with insufficient hyperopia reserve, these factors explained only 28.0% of the SE variance.CONCLUSION: In non-myopic Uyghur students aged 4-14 in Hotan County, Xinjiang, the detection rate of insufficient hyperopia reserve was 67.77%. In the group with insufficient hyperopia reserve, age, gender, AL, and K explained only a small portion of the SE variance, suggesting that the refractive status of this population may be influenced by more complex factors.
3.Clinical features of patients with hepatolenticular degeneration aged above 35 years
Hongyun WO ; Chengwei KANG ; Lei ZHAN ; Xiaobing PU
Journal of Clinical Hepatology 2024;40(1):116-120
ObjectiveTo investigate the clinical features of patients with hepatolenticular degeneration (HLD) aged above 35 years. MethodsA retrospective analysis was performed for the clinical data of the patients with HLD, aged above 35 years, who attended West China School of Public Health, Sichuan University, from April 2018 to April 2023, and according to their clinical symptoms, they were divided into mixed type group with 13 patients, liver type group with 12 patients, and brain type group with 5 patients. Related data were collected, including general information (sex, clinical manifestation, age at confirmed diagnosis, time from initial symptoms to confirmed diagnosis, and family history), laboratory examination (routine blood test, liver and renal function, serum copper, serum ceruloplasmin, urinary copper, and coagulation function), and radiological examination. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups; the Fisher’s exact test was used for comparison of categorical data between groups. ResultsFor the 30 patients with HLD, the male/female ratio was 3∶1, and the mean age was 46.13±5.88 years; the patients with positive Kayser-Fleischer ring of the cornea accounted for 43.33%, and the patients with liver cirrhosis accounted for 66.67%. There were significant differences between the three groups in globulin, albumin/globulin ratio, alanine aminotransferase, prothrombin time, international normalized ratio, and activated partial thromboplastin time (F=5.893, 4.513, 4.424, 5.029, 5.248, and 4.942, all P<0.05). ConclusionMost patients are male among the patients diagnosed with HLD after 35 years of age, with the main clinical types of mixed type and liver type, and such patients tend to have poor liver and coagulation functions. For unexplained liver function abnormalities and liver cirrhosis in this age group, the indicators such as serum ceruloplasmin and urinary copper should be screened as early as possible, and liver and kidney function and coagulation function should be monitored.
4.Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells
Meng-yang CHEN ; Rui-ping HUAI ; Dan-ni YANG ; Li-jie LEI ; Qiu-lin PU ; Li-li XIONG
Acta Pharmaceutica Sinica 2024;59(2):368-373
This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (
5.Preparation and characterization of curcumin nanomicelles and evaluation of in vitro hepatoprotective activity against alcohol liver disease
Luhui LI ; Guangping GENG ; Lei XU ; Zhikun ZHANG ; Xiaohui PU
China Pharmacy 2024;35(10):1203-1208
OBJECTIVE To prepare and characterize curcumin nanomicelles (hereinafter referred to as Cur/mPEG-PBLA micelles), and to evaluate the in vitro hepatoprotective activity against alcohol liver disease (ALD). METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly(ethylene glycol)-poly(β-benzyl-L-aspartate) (mPEG-PLGA) as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed, and particle size, polydispersity index, Zeta potential, encapsulation efficiency and drug loading content were all detected. The in vitro release, pH stability, thermal stability, dilution stability, storage stability, plasma stability tests, and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects, Cur reference solution as reference, to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light, with a spherical shape and uniform distribution. The average particle size was about 140 nm, and the polydispersity index was less than 0.3. Zeta potential was (-8.15±0.05) mV; the encapsulation efficiency was (73.26±3.16)%, and the drug loading content was (4.87± 0.42)%. The cumulative release of Cur reference substance was close to 80% at 10 h; the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution; Cur/mPEG-PBLA micelles showed good dilution stability, storage stability and plasma stability, and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells; after 48 h of application, the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration (P<0.05). CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur, delayits degradation rate, and have better in vitro hepatoprotective activity against ALD.
6.Mechanism of placental polypeptide in improving ovarian function and oxidative stress in rats with premature ovarian failure
Juan JIN ; Li XIAO ; Qian PU ; Hua ZHANG ; Lei YU
China Pharmacy 2024;35(21):2609-2615
OBJECTIVE To explore the impact of placental polypeptide on the Runt-related transcription factor 3 (RUNX3)/ Notch signaling pathway in rats with cyclophosphamide-induced premature ovarian failure (POF), and its effects on ovarian function and oxidative stress. METHODS A POF rat model was induced by intraperitoneal injection of cyclophosphamide. Sixty POF rats of the model were randomly assigned to model group, low-dose (1 mg/kg) and high-dose (2 mg/kg) placental polypeptide groups, placental polypeptide plus empty vector group [placental polypeptide (2 mg/kg), empty vector (1 μg)], and placental polypeptide plus RUNX3 silencing group [placental polypeptide (2 mg/kg), RUNX3 small interfering RNA (1 μg)], with 12 rats in each group. Additionally, 12 healthy rats were selected as a control group. The intervention lasted for 4 weeks for all groups. After the final administration, the levels of sex hormones [estradiol (E2), anti-Müllerian hormone (AMH), follicle- stimulating hormone (FSH)] in rat serum and oxidative stress indicators [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS)] in ovarian tissue were measured. The pathology of rat ovarian tissue and apoptosis of ovarian granulosa cells were examined; the expression of apoptosis-related proteins [caspase-3, cleaved-caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax)and RUNX3/Notch signaling pathway-related proteins in rat ovarian tissue were detected. RESULTS Compared with the model group, the low and high doses of placental polypeptide groups showed an increase in the number of normal follicles and a marked decrease in the number of atretic follicles, with significant increases in the serum levels of E2 and AMH, the ovarian tissue levels of SOD and CAT, as well as the expression levels of Bcl-2, RUNX3 and Notch1 proteins, and significant decreases in the serum FSH levels, the ovarian granulosa cell apoptosis rate, and the ovarian tissue levels of MDA and ROS, as well as the expression levels of cleaved-caspase-3, caspase-3 and Bax proteins (P<0.05); the changes in the high-dose group were significantly more pronounced (P<0.05). Compared with the high-dose placental polypeptide group and the placental polypeptide plus empty vector group, the placental polypeptide plus RUNX3 silencing group showed a decrease in the number of normal follicles and a significant reversal of the above indicators (P<0.05). CONCLUSIONS Placental polypeptide may alleviate the symptoms of rats with POF by upregulating the RUNX3/Notch signaling pathway, improving sex hormone secretion, oxidative stress, ovarian granulosa cell apoptosis and ovarian function.
7.Establishment and Analysis of the Method for Determining Silicone Oil Content on the Surface of Rubber Closures
Xiaocong PU ; Kun REN ; Yanyan GUO ; Huangjing LIN ; Daiguo ZHAO ; Lei CHEN
Herald of Medicine 2024;43(11):1769-1773
Objective To establish a method for determining the amount of silicone oil on the surface of rubber closures,which is one of the packaging material standards in the Pharmacopoeia of the People's Republic of China.Methods The development process of the method for determining silicone oil content on the surface of rubber closures was described,taking the infrared transmission mode as example.Through method validation,the scientific and rational aspects of the method were examined.Key points of the determination method were analyzed,including the selection of quantitative peaks,selection of measurement solvent,selection of extraction solvent and conditions,selection of instrument measurement methods,selection of liquid cell windows for infrared transmission mode,selection of quantification methods,and selection of dimethyl silicone oil reference standards.Results The infrared spectroscopy mode was chosen to determine the amount of polydimethylsiloxane on the surface of rubber closures based on the peak height of the Si-CH3 bond vibration absorption at 1 260 cm-1.Cyclohexane was used as the measurement solvent.The same concentration of polydimethylsiloxane reference solution was measured using both infrared transmission mode and attenuated total reflection mode,and quantification was performed based on peak height.The results from the two measurement modes were essentially the same.The linear range of polydimethylsiloxane was about 0.3-10.0 mg·mL-1,and its correlation coefficient was 0.999 8.The average recovery of the method was 102.3%-105.6%.The LOD of polydimethylsiloxane was 0.1 mg·mL-1.The silicone oil measurement results of seven batches for rubber closures were consistent with the silicone oil amounts provided by the manufacturer.Conclusion Enterprises can choose either the infrared transmission mode or the attenuated total reflection mode to measure the amount of polydimethylsiloxane on the surface of rubber closures based on their actual conditions.
8.Progress of clinical research on neonatal platelet transfusion
Tiantian XIE ; Hongtao LEI ; Wenhua WANG ; Pu ZHAO ; Qin ZHANG
International Journal of Pediatrics 2024;51(8):543-547
Platelet transfusion is one of the critical clinical therapies of neonatal thrombocytopenia and significant preventive measures of bleeding diseases in preterm infants.The platelet transfusion rate is high in clinical practice,whereas some controversies emerge in its clinical application.Platelet transfusion decision-making should take into account the platelet count and the causes of thrombocytopenia.In addition,the presence of bleeding tendency and platelet effects on other systemic disorders should be considered.Clinicians often need to make rapid decisions about whether to transfuse platelets in a critically situation.On the basis of the comprehensive overview of issues that are closely pertinent to the field of clinical practice,this article is dedicated to elucidate the advancements in clinical research pertaining to neonatal platelet transfusions,aiming to serve as a reference for clinicians when making transfusion decisions and to chart a course for future clinical investigations.
9.Effect of ureteral wall thickness at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy
Wei PU ; Jian JI ; Zhi-Da WU ; Ya-Fei WANG ; Tian-Can YANG ; Lyu-Yang CHEN ; Qing-Peng CUI ; Xu XU ; Xiao-Lei SUN ; Yuan-Quan ZHU ; Shi-Cheng FAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1077-1081
Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.
10.Biological and genetic characteristics of three hypervirulent Klebsiella pneumoniae strains causing liver abscess
Yuqi ZHANG ; Juan WANG ; Lei HAN ; Pu LI ; Wentao MA ; Chun ZHANG ; Yali LI ; Jing YUAN ; Jin’e LEI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):885-894
[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like bla

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