Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To determine the efficacy and influencing factors of thymectomy for bulbar myasthenia gravis.Methods:The clinical data of 120 patients with bulbar myasthenia gravis admitted to the Myasthenia Gravis Comprehensive Diagnosis and Treatment Center of Henan Provincial People's Hospital from March 2018 to June 2023 were collected, with 61 males and 59 females. There were 66 patients with thymoma and 54 patients with non-thymoma. The duration of bulbar muscle involvement before operation ranged from 11 days to 108 months. Preoperative AChR-Ab was positive in 105 cases and negative in 15 cases. There were 28 cases with bulbar muscle involvement as the initial symptom and 92 cases as the non-initial symptom. There were 7 cases with crisis and 113 cases without crisis in the past. The postoperative efficacy was evaluated according to the Myasthenia Gravis post-treatment status evaluation program of the American Myasthenia Gravis Society. Univariate analysis and logistic regression analysis were used to analyze the factors that may affect the surgical efficacy. Results:All 120 patients successfully underwent extended thymectomy, there was no perioperative death. The follow-up time was 3-57 months, with a median of 24 months. Twenty-two patients (18.33%) achieved complete durable remission, 1 patient (0.83%) maintained remission, 65 patients (54.17%) had minimal symptoms, and 20 patients (16.70%) improved. No change in 8 cases (6.67%), no aggravation cases (0), deterioration in 2 cases (1.67%), and death in 2 cases (1.67%). 23 cases(19.17%) achieved clinical remission and 85 cases (70.83%) achieved partial remission. Univariate analysis showed that positive AChR-Ab before operation and duration of bulbar muscle involvement before operation were the influencing factors of surgical efficacy in patients with bulbar MG, and the difference was statistically significant ( P<0.05). Logistic regression analysis showed that positive AChR-Ab before operation and the duration of bulbar muscle involvement before operation were independent influencing factors of surgical efficacy. Conclusion:Thymectomy can effectively relieve the symptoms of bulbar myasthenia gravis. Patients with positive AChR-Ab before surgery and shorter duration of bulbar muscle involvement may benefit more from thymectomy.

A new alkaloid (1) and six known compounds (2-7) were isolated from the solid fermentation extract of the endophytic fungus Alternaria tenuissima Pas85 of Phragmites australis by silica gel column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and other chromatographic techniques. The structures of these compounds were determined by HREIMS, NMR, IR spectroscopy, and literature comparison, and the anti MRSA (methicillin-resistant Staphylococcus aureus) activity of 1-5 were tested. Compounds 1, 2, 3 and 4 exhibited certain inhibitory activity with MIC values of 64, 4, 32 and 32 μg·mL^-1, respectively, and compound 5 showed no significant inhibitory activity.

Objective:To investigate the clinical phenotype of a child with Jansen-de Vries syndrome, to clarify its genetic diagnosis and genetic characteristics, and to improve the understanding of this disease.Methods:Clinical data from a child with Jansen-de Vries syndrome diagnosed in the Children′s Affiliated Hospital of Zhengzhou University in October 2019 were collected, using core family-complete exon genomics detection (Trio-WES) and chromosome copy number variation (CNV) analysis techniques for genetic testing for the child and her parents, generation Sanger sequencing for family member verification for possible pathogenic mutations, and clinical and molecular genetic analysis. The relevant reports of PPM1D gene mutation in patients with mental retardation were reviewed.Results:The proband was a 11-month-old girl, presenting with mental retardation, lagging speech and motor development, autistic behavior, gastrointestinal dysfunction, and short stature, low flat nose bridge, low ear, short finger syndrome.Trio-WES results of the core family of the child suggested that PPM1D was a new transcoding heterozygous mutation, PPM1D (NM-003620): c.1216delA (p.Thr406Profs *3), and the karyotype and CNV analysis of the chromosome were normal. Literature retrieval showed currently a total of 18 cases were reported PPM1D gene mutation of mental disorders, described in the online human Mendel database for developmental disorder associated with gastrointestinal dysfunction and pain threshold increases, the age distribution in the seven months to 21 years of age, clinical manifestation of mental retardation, increased pain threshold, abnormal behavior, feeding difficulties, visual impairment, short finger syndrome, a group of syndromes associated with short stature, fever or vomiting, and congenital deformities. Conclusions:Jansen-de Vries syndrome clinically presents mainly with overall retardation (mental retardation/backward delayed motor development, language development, low muscle tone), abnormal behavior (lonely sample behavior, autism), craniofacial malformations (broad forehead, low ear nose bridge, thin upper lip), short finger syndrome (short feet, pinky stubby), gastrointestinal dysfunction (milk overflow, feeding difficulties, constipation). The child was diagnosed as a newly transcoding heterozygous mutation of the PPM1D gene. The current treatment is mainly rehabilitation training, and growth hormone replacement therapy can be given to part of the short height disease. The PPM1D gene [PPM1D(NM-003620): c.1216delA(p.Thr406Profs *3)] is the genetic cause of the child.

Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.

Decision-making aid for cancer patients is of great significance in the diagnosis and treatment for diseases. Breast cancer is one of the most common malignant tumors in women all over the world, and breast cancer patients have become the main target population for decision-aided research. Application of decision-making assistance for patients in Western countries has developed to a certain extent, while relevant research in China is still at the early stage. There are kinds of intervention forms for patients' decision aids, including traditional brochures and videos, decision aids systems, decision coaching, multidisciplinary breast cancer teams, etc. The tools for decision-making quality evaluation include the patients' awareness for decision-making, participation, decision-making conflict, decision-making satisfaction, decision-making regret, which can provide important guidance for the application of decision-making aid treatment in breast cancer patients in the future.
Breast Neoplasms/therapy* ; China ; Decision Making ; Emotions ; Female ; Humans ; Personal Satisfaction

Objective To compare biomechanical properties between the anatomical clavicle plate and the reconstructed clavicle plate, and investigate the influence of pre-bending or repeated bending process on biomechanical properties of the reconstructed clavicle plate, so as to provide biomechanical evidence for treating midshaft clavicle fracture in clinic. Methods The reconstructed clavicle plate was bent by 1, 2, 3, 5 times respectively based on shape of the anatomical clavicle plate. The biomechanical differences in anatomical plate group, reconstructed plate group and pre-bending plate group were compared by static compression test. Results The fixation stiffness and strength of the anatomical plate were better than those of the reconstructed plate. There was no significant difference in stiffness and strength between the anatomical plate group and one-time bending group. Pre-bending had a great effect on mechanical properties of the clavicle plate, and stiffness and strength of the clavicle plate were obviously improved after one-time bending. The mechanical properties of the clavicle plate were obviously reduced by bending of the clavicle plate after one-time bending. Conclusions The stiffness and strength of the anatomical plate and one-time bending plate are higher than those of the normal reconstructed plate. It is recommended that surgeons should perform bending appropriately according to the patient’s clavicle anatomy when using the reconstructed clavicle plate for fracture fixation, and minimize the number of repeated bending to maintain stiffness and strength of the clavicle plate.

Objective:To explore the clinical efficacy, especially the comprehensive improvement of blood glucose and lipid of probucol and metformin in the treatment of type 2 diabetes mellitus with hyperlipidemia. Methods:Totally 105 patients with type 2 di-abetes mellitus complicated with hyperlipidemia were randomly divided into the control group1 (35 cases), the control group 2 (34 ca-ses) and the observation group (36 cases). The control group 1 was treated with diet control, exercise and metformin, the control group 2 was treated with rosuvastatin calclum tablets based on the group 1, and the observation group was treated with probucol based on the group 1. The three groups were continuously treated for 12 weeks. The improvement of the fasting blood-glucose (FPG), 2h postprandial blood glucose (PBG), hemoglobin A1C (HbA1C), fasting insulin levels (Fins), insulin resistance indices (HOMA-IR) and TC, TG and HDL-C, and the adverse reactions among the three groups were compared. Results:The total effective rate in the ob-servation group was higher than that in the control group 1 and 2 (P<0. 05). After the treatment, all the indices of blood glucose and lipid in the three groups were significantly improved (P<0. 05), and those of blood glucose in the observation were better than those in the control group 1 and 2(P<0. 05), those of blood lipid in the observation group and the control group 2 were better than those in the control group 1 (P<0. 05), and the level of HDL-C in the observation group was much higher than that in the control group 2 (P<0. 05). The adverse drug reactions in the three groups were mild without statistical significance (P>0. 05). Conclusion:Probucol as one of lipid-lowing drugs with antioxidant action combined with metformin can improve blood lipid and lower blood glucose at the same time, which is worthy of promoted application in clinics.

Objective To investigate the influence factors for immediate outcome after thymectomy for patients with myasthenia gravis (MG). Methods The clinical data of 108 patients with MG who received thymectomy in the Department of Thoracic Surgery, the Second Affiliated Hospital of Zhengzhou University from July 2009 to July 2012 were retrospectively investigated, including gender, age, duration of disease, clinical classification, pathological classification of thymus and anti-acetylcholine receptor antibodies (AChRab). The immediate outcome after thymectomy was also observed. Thirty-two cases of MG who had immediate outcome after thymectomy were enrolled into experimental group, while 76 cases who did not have immediate outcome after thymectomy were regarded as control group. Results The immediate outcome after thymectomy was associated with duration of disease (χ2=98.550, P<0.01), clinical classification (χ2=40.434, P<0.01), pathological classification of thymus (χ2=11.154, P=0.004) and AChRab (χ2=5.590, P=0.018). There were statistically significant differences between the two groups in the one-year (31.3% in the experimental group vs 14.5% in the control group, χ2=4.046, P=0.044), two-year (40.6% vs 21.1%, χ2=4.392, P=0.036) and three-year complete remission rates (46.9% vs 25.0%, χ2=4.995, P=0.025). Conclusion Duration of disease, clinical classification, pathological classification of thymus and AChRab could be influence factors for immediate outcome and complete remission for patients with MG after thymectomy.