The effect of acupuncture at the Yuji point on resting-state brain function in anxiety.

BACKGROUND: The COVID-19 epidemic has placed a lot of mental burdens on school students, causing anxiety. Clinically, it has been found that the Yuji point (LU10) can relieve anxiety by regulating Qi. METHODS: Thirty-six volunteers with anxiety disorders were divided into 3 groups, all of whom underwent 2 MRI examinations. The Yuji and nonacupoint groups received acupuncture between functional magnetic resonance imagings. We used the amplitude of low-frequency fluctuation to analyze regional brain activity, and seed-based functional connectivity (FC) to analyze changes in brain networks. RESULTS: After acupuncture, the LU10 was able to activate the frontal lobe, medial frontal gyrus, anterior cingulate gyrus, temporal lobe, hippocampus, etc in the left brain compared to the control group. The frontal lobe, medial frontal gyrus, cingulate gyrus, and anterior cingulate gyrus in the left brain were activated compared to those in the nonacupoint group. Compared with the control group, LU10 showed increased FC in the right parietal lobe, right precuneus, left temporal lobe, left superior temporal gyrus, and with cingulate gyrus. FC was enhanced among the hippocampus with the left temporal lobe and the superior temporal gyrus and reduced in the right lingual gyrus and right occipital lobe. CONCLUSION: Acupuncture at LU10s can regulate anxiety by upregulating or downregulating the relevant brain regions and networks. LU10s can be used to treat not only lung disorders but also related mental disorders.

Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19.

Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the lungs efficiently following nebulization. We have developed a high-affinity angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD-62) that can be used as a medication to inhibit infection with SARS-CoV-2 and its variants. In this study, we established a nebulization protocol for drug delivery by inhalation using two commercial vibrating mesh (VM) nebulizers (Aerogen Solo and PARI eFlow) that generate similar mist size distribution in a size range that allows efficient deposition in the small respiratory airway. In a series of experiments, we show the high activity of RBD-62, interferon-α2 (IFN-α2), and other proteins following nebulization. The addition of gelatin significantly stabilizes the proteins and enhances the fractions of active proteins after nebulization, minimizing the medication dosage. Furthermore, hamster inhalation experiments verified the feasibility of the protocol in pulmonary drug delivery. In short, the gelatin-modified RBD-62 formulation in coordination with VM nebulizer can be used as a therapy to cure SARS-CoV-2.

SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution.

SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 Å cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.

Prevalence of and risk factors associated with sleep disturbances among HPCD exposed to COVID-19 in China.

OBJECTIVE: To assess sleep disturbances and associated factors among front-line healthcare providers who have been called upon for, dispatched (HPCD) and exposed to COVID-19 in China. METHODS: This cross-sectional, survey-based, isolation area-stratified study collected demographic data, sleep status and emotional measurements from 1036 HPCD in nine medical institutions from March 5 to 9, 2020 in Wuhan, China, which was the epicenter of the epidemic. HPCD who worked in isolation areas with COVID-19 were eligible for inclusion. The severity of symptoms of sleep disorders, insomnia and emotional self-efficacy were assessed by the Chinese versions of the 10-item Self-rating sleeping situation scale, the seven-item Insomnia Severity Index and the 12-item Regulatory emotional self-efficacy questionnaire, respectively. Univariate analysis was performed to identify factors associated with sleep disturbances. A structural equation model (SEM) was constructed via AMOS to explore the relationship among the four components. RESULTS: A total of 1036 out of 1075 contacted individuals completed the survey, with a participation rate of 96.4%. A total of 925 (89.3%) were aged 20-39 years, and 755 (72.9%) were women. Among all participants, 874 (84.4%) were nurses, and 162 (15.6%) were physicians; 538 (51.9%) worked in intensive care isolation units; 843 (81.4%) worked in isolation areas for 4 h straight, and 395 (38.1%) perceived COVID-19 peer exposure. A considerable proportion of participants reported symptoms of sleep disorders (543, 52.4%). Exposure status and length of work were the main factors affecting sleep status, which had indirect effects on sleep status by mediating regulatory emotional self-efficacy. CONCLUSIONS: In this survey of HPCD for patients with COVID-19 in China, participants reported experiencing sleep disturbance burdens, especially those having exposure experience and working long shifts. Regulatory emotional self-efficacy (RESE) is an important resource for alleviating sleep disturbances and improving sleep quality. These findings emphasize the importance of being prepared to support HPCD through psychological interventions.

Risk factors associated with the progression of COVID-19 in elderly diabetes patients.

AIM: To describe the clinical characteristics and risk factors associated with the progression of COVID-19 in elderly diabetes patients. METHODS: This was a retrospective cohort study, including elderly COVID-19 patients admitted to Wuhan Huoshenshan Hospital between February 10 and 13, 2020. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. RESULTS: We included 131 elderly COVID-19 patients (50 patients with diabetes). COVID-19 diabetes patients experienced more severe pneumonia and abnormal organ functions than non-diabetes patients (P < 0.05 or P < 0.01). Most function indicators were significantly different between the mild to moderate and severely ill groups in diabetes patients (P < 0.05 or P < 0.01). Python analysis confirmed diabetes was the independent risk factor of COVID-19 progression in elderly patients. All blood glucose (BG) indices went into the risk factor equation. The cut-off values of COVID-19 progression were BG value on admission > 8.0 mmol/L or maximum BG value > 12.0 mmol/L in all elderly patients, and BG value on admission > 5.1 mmol/L or maximum BG value > 5.4 mmol/L in non-diabetes patients. CONCLUSIONS: Diabetes is an independent important risk factor, and glucose levels associate closely with COVID-19 progression in elderly patients.

Coronavirus disease 2019 associated with aggressive neurological and mental abnormalities confirmed based on cerebrospinal fluid antibodies: A case report.

INTRODUCTION: Coronavirus disease (COVID-19) is spreading worldwide. The reported possible neurological symptoms are varied and range from subtle neurologic deficits to unconsciousness. Knowledge regarding the detection, diagnosis, treatment, and follow-up of COVID-19-associated neurological damage is still limited. We report a case of serious neurological damage and mental abnormalities in a patient who was finally confirmed to have COVID-19 based on IgM and IgG antibodies in the cerebrospinal fluid (CSF). PATIENT CONCERNS: A 68-year-old man had slight flu-like symptoms and transient loss of consciousness in early February. Exaggerated unconsciousness and deteriorating mental abnormalities occurred over the next month without severe respiratory symptoms. Craniocerebral computed tomography showed normal results, but antibodies against severe acute respiratory syndrome coronavirus 2 were 100 times higher in the CSF than in the serum; tests for viral ribonucleic acid showed negative results with both a nasopharyngeal swab and CSF sample. DIAGNOSIS: COVID-19 pneumonia was diagnosed based on symptoms and positive results for IgM and IgG in the CSF. INTERVENTIONS: Antiviral, fluid, and nutritional support were administered for 30 days before admission without obvious improvement. A further 18 days of routine antiviral therapy, immunoglobulin therapy (10 g per day for 5 days), and antipsychotic drug treatment were administered. OUTCOMES: The patient's neurological and mental abnormalities were greatly ameliorated. He was discharged with mild irritability, slight shaking of the hands, and walking fatigue. These symptoms have persisted up to our last follow-up (May 4, 2020). CONCLUSION: We believe this is the first case involving neural system injury in a patient who confirmed COVID-19 based on CSF antibody test results. Negative ribonucleic acid test results, strong positivity for antibodies, and high protein levels in the CSF suggest the possibility of autoimmune encephalitis secondary to COVID-19. This case highlights additional novel symptoms of COVID-19, and these data are important for the assessment and follow-up of COVID-19 patients.