Postmenopausal osteoporosis (PMOP) is a chronic metabolic bone disease caused by a decrease in estrogen levels. With the acceleration of population aging process, the public health burden caused by it is becoming increasingly severe. The prevalence rate of osteoporosis in people over 65 years old in China is as high as 32%, which is especially prominent after menopause, which is about 5 times that of elderly men. About 40% of postmenopausal women are at risk of osteoporotic fractures, with a disability rate of up to 50% and a fatality rate of about 20%. The prevention and treatment of osteoporosis has become a major public health issue of global concern, and it is particularly urgent to develop reasonable and effective prevention and treatment programs and explore their scientific basis. Exercise is an important non-drug means for the prevention and treatment of PMOP, it can improve estrogen levels and the expression of bone formation transcription factors, and inhibit the levels of proinflammatory factors and bone resorption markers, macroscopically manifested by the improvement of bone microstructure and bone density. However, the effectiveness of exercise in improving bone mineral density (BMD) remains controversial. Some studies revealed significant changes of bone to mechanical stimulation, while others showed no significant effect of mechanical training, this heterogeneity in bone adapt to mechanical stimulation is particularly evident in postmenopausal women. Although the evidence that a wide range of exercise programs can improve osteoporosis, the optimal solution to address bone mineral loss remains unclear. The most effective exercise type, dosage and personalized adaptation are still being determined. This study will fully consider the differences in gender and hormone levels, searching and screening randomized controlled trials of PubMed, CNKI and other databases regarding exercise improving bone mineral density in women with PMOP. Strictly following the PRISMA guidelines to reviewed and compared the effects of different types of exercise modalities on BMD at different sites in women with PMOP by network Meta-analysis, to provide theoretical guidance to maintain or improve BMD in women with PMOP.

ObjectiveTo explore the effect and mechanism of modified Dingjingtang in regulating the Toll-like receptor 2 （TLR2）/nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） signaling pathway to inhibit inflammatory skin lesions in the rat model of acne. MethodsForty-eight rats were randomized into the normal， model， low-， medium-， and high-dose （8.1， 16.2， and 32.4 g·kg^-1） modified Dingjingtang， and doxycycline hydrochloride （0.27 g·kg^-1） groups， with 8 rats in each group. Rats in other groups except the normal group were modeled by intradermal injection and intraperitoneal injection of Propionibacterium acnes. After successful modeling， rats in the intervention groups were treated with corresponding agents by gavage， and those in the normal and model groups with an equal volume of normal saline， once a day for 14 consecutive days. Then， the samples were collected. The general conditions， ear thickness， and body weight changes of rats were observed. Biochemical methods were used to determine superoxide dismutase （SOD） and malondialdehyde （MDA） levels in the ear tissue. Hematoxylin-eosin staining and Masson's staining were used to observe the pathological changes and collagen deposition， respectively， in the ear tissue. Immunohistochemistry was employed to determine the interleukin （IL）-1β level in the ear tissue. Enzyme-linked immunosorbent assay was adopted to measure the levels of IL-1β， tumor necrosis factor （TNF）-α， and IL-6 in the serum. The total antioxidant capacity method was adopted to assess the reactive oxygen species （ROS） content in the ear tissue. Western blot and real-time fluorescence quantitative polymerase chain reaction were employed to determine the protein and mRNA levels， respectively， of TLR2， myeloid differentiation factor 88 （MyD88）， NF-κB， NLRP3， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in the ear tissue. ResultsCompared with the normal group， the model group had increased ear skin thickness （P<0.01）， elevated ROS and MDA levels （P<0.01）， reduced SOD content （P<0.05）， and increased collagen deposition （P<0.01） in the ear tissue. In addition， the model group showed raised IL-1β， IL-6， and TNF-α levels in the serum （P<0.01） and up-regulated mRNA and protein levels of TLR2， MyD88， NF-κB， NLRP3， and Caspase-1 （P<0.01）. Compared with the model group， the high- and medium-dose modified Dingjingtang groups showed significant improving effects regarding the above indicators （P<0.05， P<0.01）. ConclusionModified Dingjingtang can ameliorate the inflammatory skin lesions in the rat model of acne by regulating the TLR2/NF-κB/NLRP3 signaling pathway.

Objective: To investigate the Alzheimer's disease (AD) influencing factors among the elderly, so as to provide a basis for early prevention and intervention. Methods: From March to June 2024, participants aged 60 years and above from a sub-district in Haishu District, Ningbo City, Zhejiang Province were selected using a convenience sampling method. Data on demographics, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were evaluated using the short-form Geriatric Depression Scale. The Chinese Mini-Mental State Examination (MMSE) was used for the initial screening of AD, and individuals who screened positive were further diagnosed by psychiatrists. Factors affecting AD among the elderly were analyzed using a multivariable logistic regression model. Results: A total of 3 644 individuals were surveyed, comprising 1 526 males (41.88%) and 2 118 females (58.12%). The mean age was (71.85±7.44) years. AD was detected in 200 cases, with a detection rate of 5.49%. Multivariable logistic regression analysis showed that individuals aged ≥65 years (65-<70 years, OR=3.012, 95%CI: 1.007-9.012; 70-<75 years, OR=3.131, 95%CI: 1.059-9.260; 75-<80 years, OR=5.779, 95%CI: 1.989-16.784; ≥80 years, OR=16.810, 95%CI: 5.926-47.685), those who were unmarried, divorced, or widowed (OR=1.973, 95%CI: 1.383-2.815), those with hearing loss (OR=1.573, 95%CI: 1.128-2.193), those with diabetes mellitus (OR=1.958, 95%CI: 1.362-2.814), and those with depressive symptoms (OR=4.143, 95%CI: 2.997-5.728) had a higher risk of AD. Conversely, individuals with an educational level of primary school or above (primary school, OR=0.579, 95%CI: 0.401-0.835; junior high school or above, OR=0.438, 95%CI: 0.259-0.741), and those who engaged in regular physical exercise (OR=0.414, 95%CI: 0.264-0.649) had a lower risk of AD. Conclusions The detection rate of AD was relatively high among the elderly in Haishu District. AD among the elderly was related to age, educational level, marital status, physical exercise, hearing loss, diabetes mellitus, and depressive symptoms.

Objective To evaluate the expression differences of C-reactive protein(CRP),procalcitonin(PCT)and cytokines[interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin(IL)-10,IL-6,IL-4,IL-2,IL-17 A,and IFN-γ/IL-10]in human immunodeficiency virus(HIV)infection,tuberculosis(TB)infec-tion and HIV/TB co-infection in order to provide evidence for early clinical diagnosis of HIV/TB co-infection.Methods Medical records and clinical information of 103 patients with HIV(HIV group),42 patients with TB(TB group)and 67 patients with HIV/TB co-infection(HIV/TB group)were collected from January 2021 to September 2022.CRP,PCT and cytokines were detected in all patients,and their expression differ-ences among the three groups were analyzed.Receiver operating characteristic(ROC)curves were drawn and screening ability was evaluated.Results Compared with HIV group and TB group,CRP,PCT,IFN-γ,IL-10,IL-6 levels and IFN-γ/IL-10 in HIV/TB group were increased,with statistical significance(P＜0.001).Bon-ferroni correction results showed that CRP,PCT,IFN-γ,IL-6 levels and IFN-γ/IL-10 were significantly differ-ent between HIV and HIV/TB groups(all P＜0.001).ROC curve analysis showed that the area under the curve of CRP,PCT,IFN-γ,IL-6 and IFN-γ/IL-10 combined detection was 0.826,which was higher than that of single detection.Conclusion CRP,PCT,IFN-γ,IL-6,IFN-γ/IL-10 combined detection can help the early screening of HIV infection and HIV/TB co-infection.

OBJECTIVE To establish a mouse model of diabetes mellitus(DM)combined with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to investigate the important pathophysiological changes in the development of DM combined with SARS-CoV-2 infection.METHODS Wild-type(WT)mice and transgenic mice expressing the human angiotensin-converting enzyme 2 receptor driven by the cytokeratin-18 gene promoter(K18-hACE2)were randomly divided into the control group,DM group,SARS-CoV-2 spike protein(S)infection group and DM combined with S protein infection group,with 10 to 12 mice in each group.All the mice were induced by 10 weeks of high-fat diet combined with 40 mg·kg-1 streptozotocin(STZ)for 3 days by ip,except those in the control group or S protein infection group.The control group was given the same volume of 0.1 mol·L-1 sodium citrate buffer.Mice in the S protein infection group and DM+S protein infection group were additionally given 50 μL mixture of 15 μg SARS-CoV-2 spike protein and 1 g·L-1 polyinosinic-polycytidylic acid(poly[I:C])via intranasal drops,while the control group was given an equal volume of sterile water.The glucose tolerance level and pancreatic islet β cell function of mice were evaluated via oral glucose tolerance test at the 6th week of high-fat feeding and 1 week after the administration of STZ by ip.From the 6th week of high-fat feeding to 2 weeks after the administration of STZ,the random blood glucose and fasting blood glucose of mice were measured by a blood glucose meter.Blood samples were taken from subman-dibular veins of 3 mice in each group at 24,48 and 120 h after S protein infection,and lung tissues were taken after euthanization.The pathological changes of lungs of DM mice before and after S protein infection were observed by HE staining.Except for the DM group,blood samples were collected before S protein infection and at 6,24,48,72 and 120 h after infection.The levels of plasma interleukin 1β(IL-1β),IL-2,IL-6,IL-10,IL-17,interferon gamma-induced protein 10(IP-10),interferon γ(IFN-γ),tumor necrosis factor α(TNF-α),monocyte chemotactic protein-1(MCP-1)and granulocyte-colony stimulating factor(G-CSF)were detected by Luminex.The plasma levels of heparan sulfate(HS)were measured by enzyme-linked immunosorbent assay.The levels of cytokines and HS were correlated with the degree of pathological damage by Spearman correlation analysis.RESULTS STZ and high-fat diet could induce DM-like expression in mice,and the random blood glucose(P<0.01)and fasting blood glucose(P<0.05)after 1 week in the hACE2-DM group were significantly higher than in the WT-DM group,and the degree of islet function damage in hACE2-DM mice was significantly higher than that of WT-DM mice(P<0.05).Compared with the DM group,the DM+S group showed more severe pulmonary pathological changes after S protein infection,accompanied by a large number of inflammatory infiltrations and thickening of lung interstitial.Compared with the control group,the levels of pro-inflammatory cytokines G-CSF,IL-6 and IP-10 in the plasma of the WT-S group were significantly increased at 6 h after S pro-tein infection(P<0.01),and those of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 were significantly increased at 24 h after S protein infection(P<0.05).Compared with the control group,the plasma levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,MCP-1,G-CSF and IP-10 in the hACE2-S group were significantly increased at 6 h after S protein infection(P<0.05,P<0.01).IL-17 was significantly increased at 24 h and 6 h after S protein infection in the WT-DM+S group and hACE2-DM+S group,respectively(P<0.01,P<0.05).In the hACE2-DM+S group,IFN-γ and IL-1β were signifi-cantly increased in delay to 48 h(P<0.05,P<0.01),and MCP-1 was significantly increased in delay to 72h(P<0.05).Compared with the control group,the level of HS in the plasma of the WT-S group increased significantly(P<0.05,P<0.01)at 6 h and 24 h after S protein infection,but began to decrease at 48 h.At the same time,compared with the WT-S group,the HS level in the WT-DM+S group was slightly increased at 6 h after infection and decreased at 24 h.Compared with the control group,the HS level in the hACE2-S group was significantly increased at 24 h(P<0.01),as was the case with the WT-S group 24 h,48 h and 120 h after S protein infection.At 6 h,24 h and 48 h after S protein infection,the plasma HS level of the hACE2-DM+S group was significantly increased(P<0.01,P<0.05),and the duration of the increase was longer than in the hACE2-S group.Moreover,the levels of IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS in plasma were positively correlated with the degree of lung dam-age in the DM+S group.CONCLUSION In this study,the mouse model of diabetes combined with SARS-CoV-2 spike protein infection has mimicked part of the pathophysiological features of clinical patients,mainly manifested as blunted immune response and elevated HS levels with longer duration to infection alone.IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS may keep track of the course of disease in patients with diabetes combined with SARS-CoV-2 infection.

Objective To investigate the effect of dexmedetomidine(Dex)on inflammatory injury in rats with lipopolysaccharide(LPS)-induced myocarditis(Myo)by regulating AMP-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods Rats were randomly divide into the NC group,the Myo group,and the L-Dex group(10 μg/kg Dex),the M-Dex group(30 μg/kg Dex),the H-Dex group(50 μg/kg Dex),the AICAR group(100 mg/kg AMPK/SIRT1/NF-κB signal pathway activator),the H-Dex+GSK690693 group(50 μg/kg Dex+0.2 μmol/kg AMPK/SIRT1/NF-κB signal pathway inhibitor GSK690693),with 10 rats in each group.M-mode echocardiography system was used to evaluate the cardiac function of rats;ELISA kit was used to detect the levels of serum interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),and malondialdehyde(MDA)in rats;TUNEL staining was used to observe cell apoptosis;HE staining was used to observe the pathological changes of myocardial tissue;RT-qPCR was used to detect the mRNA expression of C-X-C motif chemokine ligand 1(CXCL1),C-X-C motif chemokine ligand 2(CXCL2),and vascular cell adhesion molecule-1(VCAM-1)in rat myocardial tissue;Western blot was used to detect the expression of AMPK/SIRT1/NF-κB pathway-related proteins in rat myocardial tissue.Results There was no abnormal change in cardiomyocytes in the NC group,and cardiomyocytes in the Myo group showed deformation,necrosis,inflammatory cell infiltra-tion,and mesenchymal congestion;necrosis,inflammatory cell infiltration,and mesenchymal congestion in the L-Dex group,the M-Dex group,the H-Dex group,and the AICAR group were improved compared with that in the Myo group;changes in cardiomyocytes in the H-Dex group and the AICAR group were similar to those in the NC group,and changes in cardiomyocytes in the H-Dex+GSK690693 group were similar to those in the Myo group.Compared with the NC group,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the Myo group were obviously decreased(P<0.05),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously increased(P<0.05).Compared with the Myo group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the L-Dex group,the M-Dex group,the H-Dex group and the AICAR group were obviously increased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously decreased(P<0.05),and the effects were more obvious with the increase of the dosage of Dex.There was no significant difference in the above results between the AICAR group and the H-Dex group(P>0.05).Compared with the H-Dex group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the H-Dex+GSK690693 group were obviously decreased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,levels of IL-1β,IL-6,TNF-α,MDA,cardiomyocyte apoptosis rate,the expression of CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB and NF-κB p65 protein were obviously increased(P<0.05).Conclusion Dex may alleviate LPS-induced inflammatory injury in Myo rats by up-regulating AMPK/SIRT1/NF-κB signaling pathway.

Objective To investigate the independent risk factors of postoperative femoral head necrosis for pediatric femoral neck fractures.Methods The clinical data of 122 children with femoral neck fracture who underwent surgery in our hospital from July 2008 to July 2021 were retrospectively analyzed.The femoral head necrosis was counted,and the children were divided into the femoral head necrosis group and the femoral head normal group according to the presence of femoral head necrosis,then the risk factors of femoral head necrosis were analyzed.Results Of the 122 children,22 cases(18.03％)had femoral head necrosis.The postoperative femoral head necrosis for pediatric femoral neck fractures may be related to the age,Delbet classification,initial displacement degree,injury mechanism,operation time,internal fixation method and reduction quality(P＜0.05),while which has no significant correlation with the gender,side,time from injury to operation,or reduction method(P＞0.05).The results of Logistic regression analysis showed that age＞10 years,Delbet type of Ⅰ to Ⅱ,initial displacement degree of type Ⅲ,high-energy injury and unacceptable reduction were the independent risk factors of postoperative femoral head necrosis for pediatric femoral neck fractures(P＜0.05).Conclusion Older children,or patients with Delbet type of Ⅰ to Ⅱ,large degree of initial displacement,high-energy injury,and unacceptable reduction are the independent risk factors of postoperative femoral head necrosis for pediatric femoral neck fractures.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:A SARS-CoV-2 pseudovirus(PsV)system was established for neutralizing antibody evaluation and virus entry inhibitor screening.Methods:Lentiviral vector plasmids psPAX2,pCDH-Luc and SARS-CoV-2 Spike(S)protein expres-sion plasmids were co-transfected,and harvested pseudoviral supernatant was used to infect ACE2-293T cells.Protein content of p24 was determined to reflect titer of PsV,and expression of S protein in PsV was detected by Western blot.Neutralization capacity of an S protein monoclonal antibody was evaluated using original strain,D614G,Gamma,Delta,Omicron PsV.Two reported virus entry inhibitors,chloroquine and carrageenin,were used to detect effect on entry of Omicron PsV.Results:Lentiviral vector successfully incorporated S protein.Western blot results showed that S protein mutated at 665Y showed a different cleavage form(90 kD)than wild-type full-length S protein(180 kD).Titer of PsV packaged by three plasmids system was higher.Ratio of S protein expression plasmid,transfer plasmid and packaging plasmid at 1∶3∶3 was optimum condition for viral packaging.Titer of PsV packaged under this condi-tion was over 20 ng/ml.PsV could effectively infect ACE2-293T cells,and double reporter gene GFP and firefly luciferase were expressed obviously,whose chemiluminescence values reached 106.Monoclonal antibodies of S protein effectively neutralized four types of PsVs,but neutralization of original strain was 10～30 times greater than that of variant PsV.Virus entry inhibitors,chloroquine and ι-carrageenan significantly inhibited entry of Omicron PsV.Conclusion:SARS-CoV-2 PsV infection system we conducted can simu-late entry of SARS-CoV-2 successfully.Effective pharmacodynamic evaluation of neutralizing antibodies and virus entry inhibitors can be performed efficiently by the system,which can provide a technical platform for evaluation of neutralizing antibody of SARS-CoV-2 and screening of virus entry inhibitors,and would benefit R&D of anti-SARS-CoV-2 drugs.