In recent years, a number of studies have found that the dysregulation of intestinal microbes and their metabolites plays an important role in the occurrence and development of Parkinson′s disease (PD), and is closely related to the severity of PD clinical symptoms. Short-chain fatty acids are the main metabolites of intestinal microorganisms and may be involved in the pathogenesis of PD by regulating the inflammatory response, neuronal autophagy and apoptosis and the integrity of the blood-brain barrier and intestinal barrier. In this paper, the research progresses on the role of short-chain fatty acids in the pathogenesis of PD are reviewed, in order to provide new ideas for the treatment of PD.

Objective:To investigate the clinical characteristics of circadian rhythm disorder of blood pressure and its impact on orthostatic hypotension (OH) in Parkinson′s disease (PD).Methods:A total of 165 PD patients from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to October 2021 were consecutively enrolled. Medical history and scores of motor and non-motor symptoms of patients were collected. Twenty-four-hour ambulatory blood pressure and OH data were collected, and the OH questionnaire was completed. The incidence of each type of circadian rhythm disorder of blood pressure was investigated. The t test, chi-square test and Mann-Whitney U test were used to determine between-group differences of circadian rhythm disorder of blood pressure. The linear trends in clinical characteristics were tested by linear regression analysis. Logistic regression analysis was used to analyze the relationship between different circadian rhythm disorders of blood pressure and OH as well as symptomatic OH (SOH). Results:In 165 PD patients, the incidence of reverse dipping pattern was 39.39% (65/165), nocturnal hypertension was 43.64% (72/165), and awakening hypotension was 31.52% (52/165). Compared with patients without reverse dipping pattern, patients with reverse dipping pattern were older [(71.72±7.81) years vs (65.29±9.68) years, t=-4.491, P<0.001], had later onset age [(66.67±9.10) years vs (62.16±10.66) years, t=-2.809, P=0.006], longer duration [36.00(20.50, 95.50) months vs 24.00(12.00, 41.75) months, Z=-3.393, P<0.001], higher dose of levodopa (LD) [(426.15±267.38) mg/d vs (284.00±235.58) mg/d, t=-3.590, P<0.001], higher levodopa equivalent dose (LED) [(514.80±360.03) mg/d vs (341.44±284.57) mg/d, t=-3.440, P=0.001], higher Unified Parkinson′s Disease Rating Scale (UPDRS)-Ⅱ scores (12.92±6.38 vs 9.54±5.59, t=-3.434, P=0.001), higher UPDRS-Ⅲ scores (28.34±11.60 vs 21.41±12.18, t=-3.508, P=0.001) and higher percentages of hallucinations [18.46% (12/65) vs 7.00% (7/100), χ2 =5.079, P=0.024]. Compared with patients without awakening hypotension, patients with awakening hypotension were older [(70.83±7.09) years vs (66.44±10.16) years, t=-2.811, P=0.006]. Compared with patients without nocturnal hypertension, patients with nocturnal hypertension had longer duration [39.50(15.00, 96.00) months vs 24.00 (12.00, 36.00) months, Z=-2.944, P=0.003], higher LD [(398.61±251.19) mg/d vs (294.62±254.25) mg/d, t=-2.619, P=0.010], higher LED [(493.28±344.02) mg/d vs (345.05±298.59) mg/d, t=-2.959, P=0.004], higher percentages of hallucinations [19.44% (14/72) vs 5.38% (5/93), χ2 =7.882, P=0.005], higher UPDRS-Ⅱ scores (12.08±6.33 vs 10.00±5.86, t=-2.086, P=0.039), higher UPDRS-Ⅲ scores (26.50±11.72 vs 22.42±12.66, t=-2.034, P=0.044), and greater blood pressure variability (BPV) (20.66±5.47 vs 17.44±5.36, t=-3.798, P<0.001). Trend analysis showed that the variety of circadian rhythm was positively correlated with age and duration, use of levodopa and monoamine oxidase B inhibitors and amantidine, morning and daily LD and LED, UPDRS-Ⅱ, UPDRS-Ⅲ and Hamilton Anxiety Scale scores, hallucinations, OH and SOH, and BPV in PD ( P<0.05). Multivariate Logistic regression analysis showed that awakening hypotension ( OR=3.35, 95% CI 1.55-7.22, P=0.002) and nocturnal hypertension ( OR=2.44, 95% CI 1.20-4.97, P=0.014) were risk factors for OH, and LED ( OR=1.21, 95% CI 1.01-1.43, P=0.035), UPDRS-Ⅲ scores ( OR=1.09, 95% CI 1.02-1.16, P=0.009) and w-BPV ( OR=1.14, 95% CI 1.01-1.29, P=0.029) were independent risk factors for SOH. Conclusions:Circadian rhythm disorder of blood pressure was correlated with age, duration, severity of motor symptoms. Awakening hypotension and nocturnal hypertension are independent risk factors for OH in PD.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Objective:To determine the evolution of gait impairment over the course of Parkinson′s disease (PD) by assessing the changes of gait characteristics in different disease stages, which could be helpful for disease monitoring.Methods:A total of 276 PD patients [PD group, Hoehn-Yahr (H-Y) stage 1-3] and 63 healthy controls (control group) enrolled in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2021 were included in this cross-sectional study. The gait spatiotemporal variables were recorded by a portable inertial measurement unit system. Exploratory factor analysis was performed to obtain gait domains representing different gait characteristics. One way analysis of variance was used to evaluate the differences of gait variables and gait domains among the control group and 3 different H-Y stages of the PD group, as well as the differences among the control group and 2 motor subtypes of PD in different stages. The sensitivity of different gait variables and gait domains in evaluating the severity of gait impairments at different disease stages was compared.Results:Eleven gait spatiotemporal variables were grouped in 4 gait domains: pace (step length, gait speed and stride length), rhythm/phase (cadence, stride time and double support time), pace-related variability/asymmetry [step length coefficient of variation (CV), gait speed CV and step length asymmetry] and rhythm/phase-related variability/asymmetry (swing time CV and swing time asymmetry). As the disease progresses, most evolution trends of the 4 gait domains in the tremor-dominant PD patients were consistent with those in the non-tremor-dominant subtype. Compared with the control group, PD patients at H-Y stage 1 began to show the mild impairment of rhythm/phase-related variability/asymmetry (effect size 0.42; standardized score -0.03±0.69 vs -0.33±0.49, P<0.05), especially swing time asymmetry in tremor-dominant patients; the pace domain was damaged moderately in PD patients at H-Y stage 2 (effect size 0.64; standardized score 0.12±0.80 vs 0.64±0.81, P<0.05), especially in non-tremor-dominant PD patients, but not in PD patients at H-Y stage 1 ( P>0.05). Pace-related variability/asymmetry showed great impairment in PD patients at H-Y stage 3 (effect size 0.62; standardized score 0.27±1.12 vs -0.27±0.52, P<0.05), but not in PD patients at H-Y stages 1 and 2 ( P>0.05). Conclusions:The characteristic impairments of gait in PD evolve in the process of disease progression. The rhythm/phase-related variability/asymmetry domain may be a marker to distinguish early PD from healthy controls. The pace domain and the pace-related variability/asymmetry domain are important markers to evaluate the progression of PD.

Objective:To investigate whether the presynaptic dopamine neuronal depletion in different striatal subregions predicts future development of wearing-off (WO) in Parkinson′s disease (PD) patients.Methods:A retrospective longitudinal study included 57 PD patients who were referred to the Department of Neurology of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2020, and completed 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane dopamine transporter (DAT) positron emission tomography scans at the initial evaluation and received dopaminergic drugs for at least 12 months during follow-up. The time of starting dopaminergic drug treatment and the occurrence of WO were recorded. After adjusting for clinical related factors, the predictive value of DAT uptake and related parameters in striatal subregions for WO was evaluated by Cox proportional hazards model. Results:During a median follow-up period of 23 months, 10 patients (18.18%) developed WO. Patients with WO exhibited less DAT uptake in the caudate nucleus and anterior putamen nucleus (0.66±0.52 vs 1.08±0.42, t=2.76, P=0.008 and 0.66±0.20 vs 0.87±0.28, t=2.27, P=0.027 respectively), especially in these subregions contralateral to the less-affected side of the body, compared to those without WO. Cox proportional hazard models revealed that after adjusting for gender, age, course of disease, baseline Unified Parkinson′s Disease Rating Scale Ⅲ score and increment of levodopa equivalent dosage, the lower the DAT uptake of the caudate ipsilateral to the less-affected side of the body ( HR=0.20, 95% CI 0.07-0.63, P=0.006), as well as the lower the DAT uptake of the caudate nucleus and posterior putamen nucleus ( HR=0.28, 95% CI 0.11-0.69, P=0.006 and HR=0.08, 95% CI 0.01-0.64, P=0.018 respectively) and the higher the ratio of putamen/caudate contralateral to the less-affected side of the body ( HR=2.33, 95% CI 1.02-5.33, P=0.045), the higher the risk of WO. Conclusion:The presynaptic dopamine neuronal loss, particularly bilateral caudate nucleus dopaminergic depletion at the early stage, has predictive value of development of WO in PD.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective:To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China.Methods:The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ 2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M ( Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China ( P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion:HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

Objective:To clarify the infection and epidemic characteristics of the human metapneumovirus (HMPV) in Chinese patients with febrile respiratory syndrome (FRS), and to provide important baseline data for clinical diagnosis, treatment, prevention and control of HMPV-induced respiratory tract diseases in China.Methods:FRS cases from January 2009 to June 2021 in 9 provinces in China, including Beijing, Hebei, Jilin, Shandong, Shaanxi, Xinjiang, Anhui, Guangdong, Hunan were retrospectively analyzed for their respiratory samples, clinical and epidemic data.The respiratory samples were detected for HMPV by quantitative real-time PCR.Results:A total of 11 660 cases were tested for HMPV, involving 296 (2.54%) HMPV-positive cases.Among 296 HMPV-positive cases, 218 were single HMPV infection, and 78/296 (26.35%) were co-infected with one or more respiratory viruses.HMPV mainly affected children under 5 years of age (3.10%), and in this population, the proportion of pneumonia in HMPV co-infection cases was significantly higher than that of single HMPV infection.HMPV could be detected all year round, which was more popular in winter and spring, with the peak of HMPV epidemic in March.Conclusions:HMPV is one of the important pathogens causing acute respiratory infection in children, showing a clear seasonal epidemic.HMPV can be infected alone or in combination with other respiratory viruses, which may increase the risk of pneumonia in children.

Objective:To investigate the short term outcomes and postoperative respiratory complications of patients with chronic thromboembolic pulmonary hypertension(CTEPH) treated by pulmonary endarterectomy(PEA).Methods:45 consecutive CTEPH patients underwent PEA between December 2017 and January 2020 in our institution were enrolled, including 25 females and 20 males. The mean age of operation was 51.2(25-70) years old. 24(53.5%) patients were in New York Heart Association(NYHA) functional class Ⅲ-Ⅳ. The mean PVR before operation was 923(461-2 711) dyn·s·cm -5. All patients’ data were entered in a prospective database, divieded into patients with respiratory complications group(WRC)and without respiratory complications group(WORC). To assess risk factors for postoperative respiratory complications and its effect on short term outcomes. Results:There was a significant reduction in mPAP(from 37 mmHg to 20 mmHg) and PVR(from 923 dyn·s·cm -5 to 293 dyn·s·cm -5) in the entire group. The in-hospital mortality rate was 4.4%(2 cases), died due to postoperative cardiogenic circulatory failure, even with VA-ECMO treatment and mediastinal infection, respectively. Postoperative respiratory complications occurred in 32 patients(71.1%). The most common complications were reperfusion pulmonary edema 44.4%(20 cases) and residual pulmonary hypertension 11.1%(5 cases). The WRC group showed a tendency to have longer periods of mechanical ventilation, longer ICU stays and more ICU costs. Independent predictors of postoperative respiratory complications were time from symptom onset to PEA>36 months( OR=12.2, 95% CI: 2.1-70.7, P=0.005)and six-minute walking distance<300 m( OR=12.6, 95% CI: 1.1-138.0, P=0.0038). Conclusion:Pulmonary endarterectomy is an effective and safe treatment for CTEPH. Postoperative respiratory complications were mainly determined by symptom onset time and pre-operative status. Patients with CTEPH should consider PEA surgery early.