There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

AR (androgen receptor) and CCAT2 are two prostate cancer (PCa)-related genes whereas their relationship is not yet reported. AR is the classical major functional gene in PCa progression. CCAT2, a non-coding gene, was identified based on big-data GWAS (Genome-Wide Association Studies) in the year of 2013. Androgen deprivation therapy (ADT) is usually used to treat PCa in the early stage. After persistent androgen deprivation, PCa would generally lead to castration resistant prostate cancer (CRPC), whereas the mechanism is yet unclear. Here we explore the function of AR and CCAT2 in PCa progression, especially their relation in androgen sensitive and insensitive cell model LNCap and DU145. We found a loop between AR and CCAT2 transcription by over-expression and knock-down strategies. In DU145 cells, G-CCAT2 activated AR mRNA level 2. 6 times, while T-CCAT2 inhibited it to 0. 2 times (P<0. 05). In LNCaP cells, G-CCAT2 could activate AR mRNA levels 1. 5 times, and TCCAT2 had no significant effect (P<0. 05). Under overexpression of AR in DU145 cells, the expression of CCAT2 increased 2. 9 times (P < 0. 05). The abundance of CCAT2 decreased to 0. 48 (P < 0. 05) in LNCaP cells by AR knock-down. Reporter gene analysis showed that CCAT2 could function on the AR promoter. We then performed CCK8 assays and AR protein level detection as supplement for the new gene CCAT2 studies. Finally we primarily studied some target genes that are related to AR and CCAT2 . The results showed that the G-CCAT2 transcript could activate AR expression in LNCap cells while UCCAT2 had no significant effect. In DU145 cells, G-CCAT2 exhibited a more relative stronger activation effect on AR, and U-CCAT2 could inhibit AR transcription. AR activates the transcriptional activity of CCAT2 in both cell lines, suggesting a feedback regulation between them. Our data showed that there would be a feedback loop between CCAT2 and AR, which may indicate a new method for PCa treatment.

OBJECTIVE: To test the hypothesis that β -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences". METHODS: A total of 138 participants with PQi deficiency (PQD) were randomized to receive β -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS). RESULTS: PQi status was not significantly different between the β -glucan and placebo treatment groups at baseline but improved significantly in the β -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, β -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo. CONCLUSIONS β -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).
Adult ; Double-Blind Method ; Humans ; Qi ; Risk Factors ; Self Report ; beta-Glucans/therapeutic use*

OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."
Biomarkers ; Cholesterol ; Drugs, Chinese Herbal ; Female ; Humans ; Hypercholesterolemia/drug therapy* ; Menopause

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Objective: The surgical reconstruction strategy for scar contracture deformity in chin and neck was explored, aiming to obtain better aesthetic outcome. Methods: A retrospective observational study was conducted. From December 2017 to April 2021, 34 patients with scar contracture deformity in chin and neck after burns were hospitalized in the Department of Plastic Surgery of the First Affiliated Hospital of Army Medical University (the Third Military Medical University), aged 12-54 years, including 13 males and 21 females, 4 cases with chin affected only, 7 cases with neck affected only, and 23 cases with both chin and neck affected. The scar areas were 48-252 cm². All the patients were treated by operation with expanded flaps, following the "MRIS" principle of matching of the color and thickness of the repair flaps (match), reconstructing of the aesthetic features of subunits (reconstruction), design of incision according to the plastic principle (incision), and prevention of the surgical incision scar (scar). The rectangular or kidney shaped skin and soft tissue expander (hereinafter referred to as the expander) with rated capacity of 80-400 mL was embedded in the first stage, which was routinely expanded to 3-5 times of the rated capacity of the expander. In the second stage, scar resection and expanded flap excision were performed to repair the secondary wound, and the flap donor site was sutured directly. The expansion ratio of the expander (with average value being calculated), the type of flaps used, the reconstruction of local aesthetic morphology, the appearance of postoperative incision, the survival of flap, and the situation of donor and recipient sites observed during follow-up were recorded. Results: Among the 34 patients, the average expansion ratio of the implanted expander was 3.82 times of the rated capacity of the expander. Three cases were repaired by the expanded local pedicled flap only, 19 cases by the expanded shoulder and/or chest perforator pedicled flap only, 10 cases by the expanded local pedicled flap combined with the expanded shoulder and/or chest perforator pedicled flap, and 2 cases by the expanded local pedicled flap combined with the expanded free flap of the second intercostal perforator of internal thoracic artery. After scar resection, the shapes of lower lip and chin-lip groove were reconstructed in 10 cases, chin process reconstruction and chin lengthening were performed in 16 cases, and the cervico-mental angle and mandibular margin contour were reconstructed in 28 cases. The surgical incision was concealed, most of which were located at the natural junction or turning point of the chin and neck subunits. The vertical incision of neck was Z-shaped or fishtail-shaped. All the expanded flaps in 34 patients survived after operation, of which 8 patients had minor necrosis at the edge or tip of the expanded flaps 1-3 days after operation and healed after dressing change. During the follow-up of 3-18 months, little difference in color and thickness between the expanded flap and the skin of chin and neck was observed, and the aesthetic shape of chin and neck was significantly improved, with mild scar hyperplasia of surgical incision. Conclusions: Reconstruction of scar contracture deformity in chin and neck by using expanded flaps based on the "MRIS" principle is beneficial to improve the quality of surgery and achieve better aesthetic outcome.
Chin/surgery* ; Cicatrix/surgery* ; Contracture/surgery* ; Female ; Free Tissue Flaps ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures ; Skin Transplantation ; Surgical Wound ; Treatment Outcome

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.

OBJECTIVE: To observe the effect of acupuncture-moxibustion on negative emotions and plasma tryptophan (Trip)-kynurenine (Kyn) metabolism in the patients with Crohn's disease (CD) at the mild and moderate active stage. METHODS: A total of 66 CD patients were randomized into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, acupuncture was applied in combination with moxibustion. In the control group, the sham-acupuncture was used in combination with sham-moxibustion. In both of the observation group and the control group, acupuncture was applied to Zhongwan (CV 12), Shangjuxu (ST 37), Sanyinjiao (SP 6), Gongsun (SP 4), Hegu (LI 4), Quchi (LI 11), Taixi (KI 3) and Taichong (LR 3), and moxibustion was applied to Tianshu (ST 25) and Zusanli (ST 36). The treatment was given once every two days, 3 times a week, totally for 12 weeks. Separately, before and after treatment, the score of the hospital anxiety-depression scale (HADS) and the score of intestinal core symptoms (degree of abdominal pain and frequency of diarrhea) were observed in the patients of the two groups. The concentration of plasma indoleamine 2,3-dioxygenase 1 (IDO1) and the ratios of Kyn/Trp, QuinA/Kyn, KynA/Kyn and KynA/QuinA were compared between the two groups. RESULTS: Compared with before treatment, the scores of HADS-A and HADS-D in the observation group and the score of HADS-A in the control group were all reduced after treatment ( CONCLUSION Acupuncture and moxibustion relieve the negative emotions of anxiety and depression in CD patients at mild and moderate active stage, which is probably related to the regulation of plasma Trp-Kyn metabolic pathway.
Acupuncture Points ; Acupuncture Therapy ; Crohn Disease/therapy* ; Emotions ; Humans ; Moxibustion ; Plasma ; Treatment Outcome ; Tryptophan

Objective:To explore the influence of blood pressure during peri-thrombolysis period (from admission to 24 h after thrombolysis) in intracranial hemorrhage, improvement of neurological function, primary endpoint event (recurrence of symptomatic stroke) and secondary endpoint events (complex cardiovascular and cerebrovascular events, and all-cause death) in patients with acute ischemic stroke.Methods:A total of 422 patients with acute ischemic stroke who underwent intravenous thrombolysis with alteplase during hospitalization at National Center for Stroke in Lianyungang from January 2015 to March 2019 were followed up for 90 d. According to the quintile of mean systolic and diastolic blood pressures during peri-thrombolysis period, they were divided into group of blood pressure <130.00 mmHg (Q1), group of blood pressure of 130.00-140.49 mmHg (Q2), group of blood pressure of 140.50-147.99 mmHg (Q3), group of blood pressure of 148.00-158.00 mmHg (Q4), and group of blood pressure >158.00 mmHg (Q5), and group of blood pressure <71.30 mmHg (G1), group of blood pressure of 71.30-76.19 mmHg (G2), group of blood pressure of 76.20-81.89 mmHg (G3), group of blood pressure of 81.90-90.79 mmHg (G4), group of blood pressure >90.79 mmHg (G5). Univariate and multivariate Logistic regression analyse were used to evaluate the relations of blood pressure with postoperative intracranial hemorrhage and neurological function improvement. Kaplan-Meier curve, Log-rank test and multivariate Cox proportional risk model were used to evaluate the relations of blood pressure with primary endpoint event and secondary endpoint events.Results:(1) After adjusting for confounding factors, multivariate Logistic regression analysis showed that the risk of postoperative intracranial hemorrhage in patients from Q2 was significantly lower than that in patients from Q5 ( OR= 0.160, 95%CI: 0.031-0.827, P=0.029). (2) After adjusting for confounding factors, multivariate Logistic regression analysis showed that the probability of postoperative improvement of nerve function in patients from Q2 and Q3 was significantly higher than that in patients from Q5 ( OR=2.144, 95%CI: 1.043-4.407, P=0.038; OR=2.224, 95%CI: 1.105-4.479, P=0.025); the probability of postoperative improvement of nerve function in patients from G3 and G4 was significantly higher than that in patients from G5 ( OR= 2.153, 95%CI: 1.081-4.287, P=0.029; OR=2.182, 95%CI: 1.131-4.210, P=0.020). (3) After adjusting for confounding factors, multivariate Cox proportional risk model showed that the risk of primary endpoint event in patients from Q1 and Q2 was significantly lower than that in patients from Q5 ( HR=0.079, 95%CI: 0.010-0.613, P=0.015; HR=0.211, 95%CI: 0.062-0.724, P=0.013). (4) After adjusting for confounding factors, multivariate Cox proportional risk model showed that the risk of secondary endpoint events in patients from Q1, Q2, Q3 and Q4 was significantly lower than that in patients from Q5 ( HR=0.246, 95%CI: 0.100-0.607, P=0.002; HR=0.360, 95%CI: 0.177-0.732, P=0.005; HR=0.448, 95%CI: 0.246-0.817, P=0.009; HR=0.467, 95%CI: 0.252-0.867, P=0.016). Conclusion:The risks of postoperative intracranial hemorrhage, primary endpoint event and secondary endpoint events in patients with acute ischemic stroke decrease with the decrease of systolic blood pressure during peri-thrombolysis period; moderate blood pressures (systolic blood pressure: 130.00-147.99 mmHg; diastolic blood pressure:76.20-90.79 mmHg) are beneficial for improvement of neurological function.