Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1～9 days),the intergenerational inter-val was 3 days(1～5 days),and the initial Rt was 3.0(95％CI:2.7～3.3).The incubation period of the BA.5.2 epidemic was 2 days(1～6 days),the intergenerational interval was 1 day(0～2 days),and the initial R,was 1.9(95％CI:1.7～2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P＞0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73％;if two incubation periods were detected early,the scale would have decreased by 79.56％,and if one incubation period had been delayed,the scale would have expanded by 13.72％.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04％;if two incubation periods had been detected early,the scale would have decreased by 92.47％;and if one incubation period had been delayed,the scale would have increased by 19.75％.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.

OBJECTIVE: To investigate the effect of exosomal FZD10 derived from non-small cell lung cancer (NSCLC) cells on angiogenesis of human umbilical venous endothelial cells (HUVECs) and explore the possible mechanism. METHODS: We analyzed the expression of FZD10 in two NSCLC cell lines (95D and H1299 cells), normal human bronchial epithelial cells (BEAS-2B cells) and their exosomes isolated by ultracentrifugation. Cultured HUVECs were treated with the exosomes derived from NSCLC cells or NSCLC cells transfected with FZD10-siRNA, and the changes in tube formation ability of the cells were analyzed using an in vitro angiogenesis assay. ELISA was performed to determine the concentration of VEGFA and Ang-1 in the conditioned media of HUVECs, and RT-qPCR was used to analyze the mRNA levels of VEGFA and Ang-1 in the HUVECs. The effects of exosomal FZD10 on the activation of PI3K, Erk1/2 and YAP/TAZ signaling pathways were evaluated using Western blotting. RESULTS: Compared with BEAS-2B cells and their exosomes, 95D and H1299 cells and their exosomes all expressed high levels of FZD10 (P < 0.01). The exosomes derived from 95D and H1299 cells significantly enhanced tube formation ability and increased the expressions of VEGFA and Ang-1 protein and mRNA in HUVECs (P < 0.01), but FZD10 knockdown in 95D and H1299 cells obviously inhibited these effects of the exosomes. Exosomal FZD10 knockdown suppressed the activation of PI3K and Erk1/2 signaling pathways, but had no obvious effect on the activation of YAP/TAZ signaling pathway. CONCLUSION Exosomal FZD10 derived from NSCLC cells promotes HUVEC angiogenesis in vitro, the mechanism of which may involve the activation of PI3K and Erk1/2 signaling pathways.
Carcinoma, Non-Small-Cell Lung/metabolism* ; Cell Proliferation ; Culture Media, Conditioned ; Exosomes ; Frizzled Receptors/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; MicroRNAs/genetics* ; Neovascularization, Pathologic/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering/metabolism*

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

OBJECTIVE: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. METHODS: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. RESULTS: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. CONCLUSION HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).

OBJECTIVE: To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex (FA-2-b-β) of Agaricus blazei Murrill extract. METHODS: CCK-8 method was used to detected the inhibitory effect of FA-2-b-β on proliferation of primary CML cells from newly diagnosed CML patients, the CML mouse model was established by trail-venous injection of primary CML cells, and the survival time, blood cell count and body weight were observed, the immunoflouresence and immunehistochemistry analysis, RT-qPCR, Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins. RESULTS: The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration- and time-dependent manner (r CONCLUSION The FA-2-b-β can induce apoptosis of primary CML cells and prolong the survival time of CML model mouse, which may be related with the caspase-3 signal pathway related genes and proteins.
Agaricus ; Animals ; Apoptosis ; Cell Proliferation ; Humans ; Imatinib Mesylate ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mice

Objective: To investigate the vascular anatomy of the stomach, especially the right gastroepiploic artery for the reconstruc-tion of a gastric tube during esophagectomy. Methods: The vascular anatomy of the stomach was studiing in 28 embalmed human specimens provided by the Department of Anatomy, Shanghai Medical College, Fudan University, included 10 female and 18 male spec-imens. The length and diameter of gastric vessels were measured. The ratio of the length of the right gastroepiploic artery to the length of the greater curvature was calculated. Anastomosis between the left and right gastroepiploic arteries was also assessed. Re-sults: Twenty-five left gastric arteries were observed in the autopsies, with the mean diameter of 3.40 (2.10-6.40) mm. Twenty-one right gastric arteries were measured, with the mean diameter of 1.97 (0.68-3.56) mm. Twenty-six left gastroepiploic arteries were ob-served, with the mean diameter of 1.87 (0.80-2.96) mm. Twenty-eight right gastroepiploic arteries were measured, with the mean di-ameter of 2.82 (1.58-4.80) mm. The mean lengths of the 28 right gastroepiploic arteries and their greater curvatures were 216.71 (120-318) mm and 356.39 (248-487) mm, respectively. The ratio of the length of right gastroepiploic arteries and greater curvatures was 0.61 (0.45-0.82). The anastomosis between the left and right gastroepiploic arteries was observed in 60.7% (17/28) of the specimens. Conclusions: The length and diameter of gastric vessels were calculated. It was assumed that the right gastroepiploic artery provides an average of 61% of the blood supply for the great curvature. In addition, the anastomotic branch of the right and left gastroepiploic arteries was observed in 60.7% specimens. These anatomical data allow surgeons to estimate the blood supply and to choose an opti-mal method of gastric tube reconstruction during esophagectomy.