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

OBJECTIVE To establish anticoagulation pharmaceutical service model based on the integrated theory of health behavior change （ITHBC）， and analyze its effects. METHODS Referring to relevant literature and soliciting opinions from 8 experts from departments such as pharmacy， respiratory medicine， and vascular surgery， a anticoagulation pharmaceutical service model based on ITHBC was ultimately formed. VTE inpatients were selected from The First Affiliated Hospital of Shihezi University from December 2023 to June 2024 as the research subjects. They were randomly assigned into intervention group （58 cases） and control group （60 cases） using a random number table method. The intervention group implemented pharmacist-led anticoagulant pharmaceutical service model based on ITHBC， while the control group adopted a conventional anticoagulant pharmaceutical service model. The anticoagulation-related outcomes of two groups were compared after 3 months： anticoagulation compliance rate， the incidence of adverse drug reactions， the score of medication adherence and compliance rate of anticoagulant prescription； economic evaluation was conducted. RESULTS After implementing ITHBC-based anticoagulant pharmaceutical services for 3 months， the intervention group had higher anticoagulation compliance rate， score of medication adherence， and compliance rate of anticoagulant prescription than the control group （P＜0.05）. There was no statistically significant difference in the total incidence of adverse drug reactions between the two groups （P＞0.05）. For every 1% point increase in anticoagulant compliance rate， the hospital needed to invest 4.35 yuan additionally in anticoagulant pharmaceutical service fees. Compared with China’s per capita gross domestic product （GDP， 89 358 yuan） in 2023， the incremental cost-effectiveness ratio value that increased the anticoagulation compliance rate by 50% is far less than one time of per capita GDP. CONCLUSIONS The pharmacist- led anticoagulant pharmaceutical service model based on ITHBC can effectively improve the outcomes of anticoagulant therapy for VTE patients， enhance medication compliance， improve patients’ awareness and recognition of adverse drug reactions to anticoagulants， and has certain economic and social benefits.

Neck dissection and reconstruction are two important aspects of oral cancer treatment.There are various surgical methods for neck dissection and reconstruction,but all of them are performed by open surgery.This article reports a full endoscopic neck dis-section through the retroauricular hairline approach,the radical resection of the intraoral tumor and the repair of the defect by superfi-cial circumflex iliac artery perforator flap with in situ vascular anastomosis intraorally.The incision is located in the hairline,hidden and invisible,and there is no exposed surgical scar on the neck after surgery.This paper introduces the technique of scarless neck dissection combined with free skin flap repair for the treatment of oral cancer and discusses its advantages and disadvantages.

In order to investigate the changes in lipid metabolism of the host after infection with porcine epidemic diarrhea virus(PEDV),blood,intestinal and cellular samples were collected from PEDV-infected piglets and Vero cells,and the levels of triglyceride(TG)and total cholesterol(TC)were detected by blood biochemical analyses,flow cytometry,and immunofluorescence,and changes in the gene levels of the enzymes related to lipid metabolism of the hosts were detected by qPCR.The results showed that PEDV infection significantly elevated host total lipid levels and sig-nificantly promoted the expression of enzymes related to fatty acid and cholesterol metabolism in the intestine and Vero cells of piglets.In conclusion,PEDV infection leads to an increase in host to-tal lipid levels,remodeling of lipid metabolism in piglets intestine and Vero cells,and lipid metabo-lism gene changes.The results of this study show that lipid metabolism-related genes can be used as a key target to influence PEDV replication,which will provide a new theoretical basis for the subsequent prevention,control and treatment of PEDV infection.

Objective To explore the effects of Manchester pain management on postoperative pain and recovery in pregnant women with gestational hypertension.Methods In total,134 pregnant women with gestational hypertension admitted to the Obstetrics Department of Shengjing Hospital between April 2022 and May 2023 were selected.The patients were randomly divided into a control group(group C)and a Manchester group(MPMM group).Pain frequency,pain(VAS),anxiety(SAS),depression(SDS),and sleep quality(PSQI)scores,as well as morning systolic blood pressure(SP),diastolic blood pressure(DP),mean arterial pressure(MAP),first time out of bed,and hospitalization time were recorded and compared between the two groups on days 0,1,and 3 after surgery.Results The pain score and frequency of pain in the MPMM group were lower than those in the C group on days 0 and 1 after surgery(P<0.05);the SAS and PSQI scores were lower in the C group on days 1 and 3 after surgery(P<0.05);and the SDS scores on days 0,1,and 3 after surgery were lower than those in the C group(P<0.05).On days 0,1,and 3 after surgery,the SP in the MPMM group was lower than that in the C group;the DP and MAP were lower than those in the C group on days 1 and 3 after surgery,and the first time of getting out of bed and hospitalization time were significantly shorter than those in group C(P<0.05).Conclusion The MPMM alleviates postoperative pain,reduces anxiety and depression,improves sleep quality,and promotes early recovery in pregnant women with gestational hypertension.

Objective To construct a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer and to evaluate its efficacy.Methods Through literature review and Delphi expert correspondence,a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer was constructed.By the convenience sampling method,200 consecutive children who received chemotherapy in the neurosurgery department of a tertiary children's hospital in Zhejiang province from February 1 to October 31,2023 were included as the application subjects,with 100 cases in an experimental group and 100 cases in a control group.The experimental group applied the non-drug intervention program of acute chemotherapy-related nausea and vomiting in children with cancer,and the routine measures were applied in the control group.The incidence of nausea and vomiting,severity of vomiting,compliance rate of normal sleep duration and incidence of negative emotions were compared between the 2 groups.Results The recovery rate of the valid questionnaire in 2 rounds of expert letter inquiry was 100％,and the expert authority coefficient was 0.836.The Kendall harmony coefficients were 0.471 and 0.820(P＜0.001),and the final non-drug intervention program for pediatric acute chemotherapy-related nausea and vomiting included 5 primary,14 secondary and 18 tertiary items.The results showed that the incidence of nausea,vomiting and negative emotions in the experimental group were lower than that in the control group,with statistically significant differences(P＜0.05).The severity of vomiting was less than it in the control group,with statistically significant difference(P＜0.05).The standard rate of normal sleep time was higher than that of the control group,and the difference was statistically significant(all P＜0.05).Conclusion The non-drug intervention program of chemotherapy-related nausea and vomiting in children is scientific and feasible,and the implementation of the program can reduce the incidence of nausea,vomiting and negative emotions,reduce the severity of vomiting,and improve the standard rate of normal bedtime in children.

Objective To investigate the prenatal diagnosis and perinatal outcomes between anterior pla-centa accreta and non-anterior placenta.Methods A retrospective analysis was done for 560 pregnant women who were diagnosed with placenta accreta and delivered in the Third Affiliated Hospital of Guangzhou Medical Uni-versity.According to the location of the placenta,the group was dividing into anterior placenta accreta group(319 cases)and non-anterior placenta accreta group(241 cases).The general characteristics,maternal and infant out-comes of the two groups were analyzed.The non-anterior placenta accrete group(241 cases)then were dividing into two groups according to the time of clear diagnosis.Those who were firstly diagnosed with placenta accrete dur-ing or after the operation was the intrapartum diagnosis group(missed diagnosis)(70 cases),and those who were diagnosed with clear placenta accreta before the delivery was prenatal diagnosis group(171 cases).The general characteristics,maternal and infant outcomes of the two groups were also analyzed.Results There were statisti-cally significant differences in the parity,history of cesarean section,delivery mode,degree of placenta accreta,missed diagnosis rate,neonatal birth weight,and hysterectomy rate between the non-anterior placenta accrete group and the anterior placenta accreta group.In the case of prenatal diagnosis of different degrees of placenta accreta,the prenatal diagnosis rate of placental adhesion in the non-anterior placenta accreta group was lower than that of the anterior placenta accreta group,which was statistically significant.In the non-anterior placenta accrete group,there were statistically significant differences in the age,cesarean section history,placenta previa status,mode of delivery,degree of implantation,24-hour bleeding volume,blood transfusions,NICU transfer rate,uterine loss rate between the intrapartum diagnosis group(missed diagnosis)and the prenatal diagnosis group.Conclusions The high-risk factors of patients with non-anterior placenta accreta are different from those of patients with anterior placenta accreta.Multiple births and a history of cesarean section are high-risk factors for anterior placenta accreta patients.Non-anterior placenta accreta are more likely to be missed diagnosed,especially the placental adhesion.For pregnant women with non-anterior placenta accreta missed diagnosis,there is a high rate of adverse birth out-comes,especially in the rate of neonatal transfer to the NICU.

To investigate the safety and feasibility of gasless total endoscopic resection of deep lobe parotid gland tumors via a postauricular hairline plus temporal approach. The approach was designed as: a 4 to 5 cm main incision was designed at the postauricular hairline, and a 0.5 cm auxiliary incision was designed in the temporal hairline. The operating cavity was established with the assistance of a special retractor. "Anterograde" dissection of the facial nerve was performed throughout the procedure, along with partial or total gland removal of the tumor. All 16 operations were successfully completed without conversion to open surgery. During the operation, the trunk and branches of the facial nerve were completely preserved, the tumor was completely removed, and the incision healed. Six patients had mild facial paralysis after operation, and recovered completely after 3 to 6 months. There was no salivary fistula, Frey syndrome, infection, or other complications. The postoperative incision was concealed and the aesthetic effect was good. The postauricular hairline plus temporal approach gasless total endoscopic parotidectomy is safe and feasible. This technique can achieve the complete dissection of the total trunk to the branches of the facial nerve, and has good access to the tumors located in any part of the parotid gland region. On the basis of radical resection of the tumor, it achieves minimally invasive and aesthetic improvement.

Objective To evaluate iron deposition in gray matter nuclei in patients with cerebral small vessel disease(CSVD)based on quantitative susceptibility mapping(QSM)and to analyze its correlation with cognitive function.Methods Patients with CSVD attending the outpatient clinic in the Department of Neurology at Xuanwu Hospital of Capital Medical University from December 2016 to November 2022,and healthy controls recruited from previous studies in the Department of Radiology and Nuclear Medicine at Xuanwu Hospital of Capital Medical University from September 2022 to November 2022 were retrospectively consecutively collected.Baseline data of CSVD patients and healthy controls was collected and compared,including age,sex,past history(hypertension,diabetes,hyperlipidemia),smoking history,alcohol consumption history and Montreal cognitive assessment(MoCA)scale score.MRI of all CSVD patients and healthy controls were collected,including three-dimensional T1 weighted imaging,QSM,T2 weighted imaging,and fluid attenuated inversion recovery(FLAIR)sequence imaging.According to the MRI-related imaging features and CSVD total burden score,the patients were divided into mild CSVD(CSVD-m)group and severe CSVD(CSVD-s)group,and healthy controls were the control group.QSM was used to obtain the susceptibility values of gray matter nuclei for all CSVD patients and controls.One-way covariance analysis and Bonferroni correction were used to compare the gray matter nuclei susceptibility values among the three groups.Spearman correlation analysis was performed between susceptibility values of gray matter nuclei with statistically significant differences in susceptibility values and cognitive function.Results A total of 61 cases of CSVD patients were included,including 29 cases in the CSVD-s group and 32 cases in the CSVD-m group;32 healthy controls were included in the control group.(1)There was no statistically significant difference in age,sex,hypertension,diabetes,hyperlipidemia,smoking,and alcohol consumption between the CSVD-s group,CSVD-m group and control group(all P＞0.05).The MoCA scale scores of the CSVD-s group and CSVD-m group were lower than those of the control group(25.0[22.5,27.5]points,27.0[25.0,29.0]points than 28.0[27.0,29.0]points,H=15.006,P＜0.01).The difference in the imaging features distribution of cerebral microbleeds,white matter hyperintensity,and perivascular space among the CSVD-s group and the CSVD-m group was statistically significant(all P＜0.05).(2)The differences in susceptibility values of the left putamen(F=4.790),pallidus(F=12.896),hippocampus(F=3.904)and the right putamen(F=36.278),pallidus(F=39.449),caudate nucleus(F=6.797),and thalamus(F=6.525)were statistically significant among the three groups(all P＜0.05).After Bonferroni correction,the susceptibility values of the left putamen and pallidus and the right putamen,pallidus,caudate nucleus,and thalamus in the CSVD-s group were higher than those of the control group(all P＜0.05);the susceptibility values of the left pallidus and the right pallidus,putamen,and thalamus in the CSVD-m group were higher than those of the control group(all P＜0.01),and the left hippocampus was lower than that of the control group(P=0.045).(3)The susceptibility values of the bilateral putamen were significantly negatively correlated with MoCA scale score(left putamen:rs=-0.316,P=0.015;right putamen:rs=-0.316,P=0.014).Conclusion Abnormal iron metabolism occurs in gray matter nuclei of CSVD patients,and iron deposition in the putamen correlate with cognitive dysfunction.

Objective:To seek specific response points on the body surface of patients with primary dysmenorrhea(PD)by observing blood perfusion unit(PU)at different points of the three Yin meridians of foot using laser speckle contrast imaging(LSCI). Methods:Eighty PD patients were recruited as a PD group,and 80 healthy female undergraduates were taken as a normal group.During one menstrual cycle(before menstruation,during menstruation,and 3 d after menstruation),each participant was examined using the LSCI system to determine PU at bilateral Taixi(KI3),Taibai(SP3),Taichong(LR3),Shuiquan(KI5),Diji(SP8),Zhongdu(LR6),Sanyinjiao(SP6),and Xuehai(SP10)and non-acupuncture points.The researchers in charge of point location,operation,and statistical analysis were not aware of grouping.PU at the detection spots was taken as the outcome measure. Results:Compared with the normal group,the PD group showed increases in PU at right Taixi(KI3)before menstruation(P<0.05)and at bilateral Zhongdu(LR6)and right Diji(SP8)during menstruation(P<0.05).At the other time points,significance was not found between the two groups in comparing PU at the detected spots. Conclusion:Compared with healthy participants,PD patients present specific changes in PU at Taixi(KI3),Diji(SP8),and Zhongdu(LR6)at specific time points during the menstrual cycle,which provides a reference for acupuncture-moxibustion treatment of PD in clinical settings.