Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To explore the autoregulation mechanism of cerebral blood flow in a patient with asymptomatic orthostatic hypotension after cervical spinal cord injury.Methods The patient underwent an upright tilt experiment to measure brachial artery blood pressure,cerebral blood flow parameters were monitored by TCD,and cerebral vascular resistance(CVR)was calculated.Results The data showed that the patient's blood pressure,right middle cerebral artery systolic peak flow velocity(Vs),end diastolic blood flow velocity(Vd),mean blood flow velocity(Vm),pulsatile index(PI),and CVR were normal in the supine position.However,when tilted at 30°,60°,and 90°,blood pressure,Vs,Vd,Vm,and CVR decreased,while PI increased.Conclusion When the patient with asymptomatic orthostatic hypotension after cervical spinal cord injury experiences with orthostatic hypotension,the cerebral vascular constricts and cerebral blood flow reduces.

Objective: We used polysomnography (PSG) monitoring and neuropsychological scales to explore the characteristics of coronavirus disease-2019 (COVID-19) patients diagnosed with post-traumatic stress disorder (PTSD) in Wuhan, two years after the onset of the COVID-19 pandemic. Methods: A total of 42 patients in the Sleep Medicine Center were diagnosed with insomnia between December 2021 and May 2022; they were divided into the PTSD group (patients with PTSD diagnosed with insomnia after COVID-19 infection) and the non-PTSD group (patients with insomnia without PTSD). A healthy control group was simultaneously included. Results: The PTSD group was more significant than the non-PTSD group in partial manifestations of sleep disorders, neuropsychological clinical symptoms, and partial PSG data. Patients with different COVID-19 subtypes showed significant differences in the course of disease, sleep disorders, neuropsychological clinical symptoms, relevant scale scores, and PSG data analysis. Conclusion The emotional anxiety and depression of COVID-19 patients diagnosed with PTSD two years after the COVID-19 pandemic in Wuhan are more significant, and will not be self-alleviated with the passage of time. It is necessary to continue to pay attention to the PTSD symptoms and sleep psychology of COVID-19 infected patients, and take appropriate measures. Patients with severe and critical COVID-19 have more severe sleep and mental disorders, and there is a significant correlation between the duration of the disease and the severity of mental and mental disorders and sleep disorders after recovery.

Objective To explore the effects of drug therapy combined with multi-dimensional psychological intervention on the insomnia of shift medical staff in"sunshine hospital"mode,and to provide a reference for improving the physical and mental health of shift medical staff.Methods A total of 140 cases of medical staff with insomnia in shifts in Wuhan were included and divided into study group and control group by random number table method,70 cases in each group.The control group was given drug treatment,and the study group was treated combined with multi-dimensional psychological intervention.based on"sunshine hospital"model.The scale and questionnaire of PSQI,ISI,ESS and FAS were used to evaluate sleep status and HAMD,HAMA,PHQ-9 and SAS were used to evaluate psychological status,at baseline,visit 1(baseline+intervention for 1 month)and visit 2(baseline+intervention for 3 months),respectively.Results(1)Sleep status:There were differences in 7 dimensions of PSQI score,ISI,ESS,and FAS score between the study group and the control group at different periods(P<0.05);Among them,the PSQI scores of the two groups showed significant difference between the two groups at interview 2(P<0.05);There were significant differences in sleep quality,sleep efficiency scores,ESS and FAS between the two groups at visit 1 and visit 2(P<0.05).(2)Psychological status:HAMD,HAMA,PHQ-9 and SAS scores of the study group and the control group were different in different periods(P<0.05).At interview 2,there were significant differences in HAMA and SAS scores between the two groups(P<0.05).Conclusion Based on the"sunshine hospital"model of drug therapy combined with multi-dimensional psychological intervention,it can significantly improve sleepiness,fatigue symptoms,sleep quality,sleep efficiency,and anxiety and depression of first-line shift medical staff in the short term,and significantly alleviate overall insomnia and anxiety in the long term.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To explore the clinical significance of event-related potential P300 in the diagnosis and treatment of cognitive function in patients with chronic insomnia combined with anxiety and depression.Methods:Sixty patients with chronic insomnia complicated with anxiety and depression treated in Wuhan First Hospital from October 2020 to March 2021 were selected as the observation group, and 60 healthy volunteers were selected as the control group in the same period.Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) were used to evaluate the anxiety and depression status of patients.Mini mental state examination (MMSE) and Montreal cognitive assessment scale (MoCA) were used to evaluate the cognitive function of the subjects.All subjects were tested for P300 event-related potential, and the latency and amplitude of P300 event-related potential were recorded.SPSS 25.0 software was used for statistical analysis.Independent sample t-test was used for comparison between groups.Pearson correlation analysis was used to analyze the correlation between cognitive function and P300 event-related potential. Results:The scores of HAMA ((16.65±5.10), (9.30±4.42)) and HAMD ((18.07±3.97), (8.48±3.21)) in the observation group were higher than those in the control group ( t=8.438, 14.545, both P<0.05), and the MoCA score (22.35±4.25) was lower than that(25.65±2.29) in the control group ( t=-5.291, P<0.05). In the eight dimensions of MoCA, the scores of visual space and executive ability ((3.38±1.46), (4.63±0.69)), naming ((2.37±0.78), (2.65±0.48)), language ((2.17±0.96), (2.53±0.81)) and delayed recall ((2.58±1.45), (4.17±0.85))in the observation group were lower than those in the control group ( t=-5.991, -2.394, -2.259, -7.292, all P<0.05). Compared with the control group, the latencies of P300 (N1, N2, P3) in the observation group were significantly prolonged ( t=3.281, 4.342, 4.492, all P<0.01). The latencies of P300 (N1, N2, P3) were positively correlated with HAMD score ( r=0.242, 0.301, 0.311, all P<0.05). The latencies of P300 (N2, P3) were positively correlated with HAMA score ( r=0.205, 0.207, both P<0.05). The latencies of P300 (N2, P3) were negatively correlated with the delayed recall score of MoCA ( r=-0.197, -0.236, both P<0.05). Conclusion:There are different degrees of cognitive impairment in patients with chronic insomnia combined with anxiety and depression.P300 in patients with chronic insomnia combined with anxiety and depression shows prolonged latency.P300 latency is related to depression, anxiety and cognition in patients with chronic insomnia combined with anxiety and depression.Event-related potential P300 may be used as a neurophysiological objective evaluation tool for cognitive impairment in patients with chronic insomnia combined with anxiety and depression.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Objective:To explore the effect of repetitive transcranial magnetic stimulation(rTMS) combined with cognitive behavioral therapy for insomnia(CBT-I)for menopausal women with insomnia.Methods:A total of 76 menopausal women with insomnia who were hospitalized from April 2020 to October 2021 were enrolled.Then they were randomly divided into observation group and control group, with 38 cases in each group.Both observation group and control group were treated with CBT-I. Meanwhile, the patients in observation group were treated with low-frequency repetitive rTMS, on the contrary, the patients in control group were treated with sham rTMS.The intervention lasted for 4 weeks.Insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI) and polysomnography (PSG) were all recorded at baseline and 4 weeks after intervention, as well as adverse events. Data was analyzed by SPSS 22.0 software. Data which was normally distributed, was compared by independent t-test and paired t-test. Results:(1)The scores of ISI (16.39±4.03, 15.66±4.89) and the PSQI(14.97±2.70, 14.11±3.60) in observation group and control group at baseline were not significantly different( t=-0.716, -1.190, both P>0.05). After treatment, the ISI and PSQI scores of the observation group (10.08±3.65, 9.58±1.73)were lower than those of the control group (12.82±4.47, 12.13±2.32), and the differences were statistically significant ( t=2.926, 5.440, both P<0.05). (2) After treatment, all sleep parameters were significantly improved from baseline in observation group (all P<0.05). Sleep efficiency, wake time during sleep, and number of awakenings were significantly improved from baseline in control group(all P<0.05). Compared with control group((70.38±12.99)%, (17.39±11.75)%, (13.98±6.35)%), the observation group reported a greater statistically improvement in sleep efficiency, N3% and REM%((79.52±9.31)%, (22.80±6.05)%, (18.78±6.68)%, respectively)( t=-3.526, -2.524, -3.212, all P<0.05). Neither group had serious adverse effects. Conclusion:The rTMS combined with CBT-I can significantly improve the sleep quality in menopausal women with insomnia. With its high safety rTMS combined with CBT-I may be a recommended non-drug therapy among menopausal women with insomnia.

Objective:To explore the prevalence of hepatitis C virus (HCV) infection, influence factors and interaction on HCV infection in patients receiving methadone maintenance treatment (MMT) in Taiyuan.Methods:Between April-June 2019, three MMT clinics in Taiyuan were selected to conduct a face-to-face questionnaire survey among MMT patients to collect the information about their socio-demographic characteristics, drug use, MMT, sexual behavior and health status. Software EpiData 3.1 was used for real-time double entry to establish the database. Software SAS 9.4 was used to analyze the data, and χ 2 test was used for univariate analysis and logistic regression model was used for multivariate and interaction analyses. Results:A total of 903 subjects were surveyed among MMT patients, the male to female ratio of was 7.21∶1(743∶103), and the rate of HCV infection was 12.53% (106/846). After adjusting for the confounding factors, being women ( OR=1.936, 95% CI: 1.023-3.662), having sex with drug users ( OR=2.073, 95% CI: 1.110-3.871) and injection drug use ( OR=7.737, 95% CI: 4.614-12.973) might be the risk factors for HCV infection in patients receiving MMT. The results showed that there were multiplicative interactions among women, having sex with drug user and injection drug use on HCV infection. Conclusions:Being women, having sex with drug user and injection drug use were associated with higher risk for HCV infection in patients receiving MMT in Taiyuan. There were multiplication interactions between being women and having sex with drug user, being female and injection drug use, and having sex with drug use and injection drug use on HCV infection.

Objective To investigate the clinical value of arterial first approach in laparoscopic pancreaticoduodenectomy (LPD) for periampullary tumor. Methods The data of 134 patients with periampullary tumor who had underwent LPD between February 2014 and August 2017 were collected. The patients were divided into 2 groups by random digital table method, with 67 cases in each group. The experimental group received arterial first approach LPD, and the control group received traditional approach LPD. The intraoperative, postoperative and survival situations were compared between 2 groups. Follow- up using outpatient examination and telephone interview was performed to detect the tumor- free survival up to February 2018. Results All the patients underwent successful LPD. The time of tumor resection with superior mesenteric venous invasion, volume of intraoperative blood loss and volume of blood transfusion in experimental group were significantly lower than those in control group: (215.6 ± 12.3) min vs. (263.4 ± 21.2) min, (98.9 ± 15.6) ml vs. (130.1 ± 26.7) ml and (1.4 ± 0.9) U vs. (2.9 ± 1.3) U, and there were statistical differences (P<0.05). The rate of R0 resection in experimental group was significantly higher than that in control group: 97.0％ (65/67) vs. 88.1％ (59/67), and there was statistical difference (P<0.05). There was no statistical difference in postoperative 6- month tumor- free survival rate between 2 groups (P>0.05). Conclusions Arterial first approach in LPD can significantly reduce the volumes of intraoperative blood loss and blood transfusion, shorten the time of tumor resection with superior mesenteric venous invasion, and increase the rate of R0 resection.