BACKGROUND:Chinese herbal prescription with head acupuncture exercise therapy has significant clinical efficacy in the treatment of limb spasticity after ischemic stroke;however,the exact mechanism is not clear.OBJECTIVE:To explore the possible mechanism of the combination of Chinese herbal prescription with head acupuncture exercise therapy in improving limb spasticity after stroke.METHODS:Seventy Sprague-Dawley rats were divided into blank,model,exercise therapy,head-acupuncture,Chinese herbal prescription,Chinese herbal prescription with head acupuncture exercise therapy,and sham-operation groups using the random number method,with 10 rats in each group.Except for the blank group and the sham-operation group,a rat model of cerebral ischemia/reperfusion injury was made by using the middle cerebral artery cable embolism method in the rest of the groups.Interventions in each group started on the 3rd day after modeling.In the Chinese herbal prescription group,rats were given 1.5 g/kg Yi'nao Fujian herbal prescription by gavage;in the head acupuncture group,acupuncture was applied to Baihui and 2 mm on the left and right sides of Baihui,and was left in place for 30 minutes;in the exercise therapy group,rats were exercised on a treadmill for 30 minutes;in the Chinese herbal prescription with head acupuncture exercise therapy group,1.5 g/kg Yi'nao Fujian herbal prescription was given by gavage followed by acupuncture treatment(identical to that in the head acupuncture group,and then the animals were exercised for 30 minutes on the treadmill while the acupuncture needles remained in place.Rats in the model and sham-operation groups were subjected to grasping under the same environmental conditions and placed on a rat immobilizer for 30 minutes,and the blank group did not have any intervention.The frequency of intervention in each group was once a day for 7 consecutive days.The neurological deficit score and muscle tone were evaluated in each group before and after treatment.Pathological changes in rat brain tissue were observed.Protein and mRNA expressions of glutamic acid decarboxylase 67,succinate semialdehyde dehydrogenase,and γ-aminobutyric acid transaminase in the cerebral cortex of the rats were detected.RESULTS AND CONCLUSION:(1)Compared with the model group,the Chinese herbal prescription with head acupuncture exercise therapy group had lower neurological deficit scores and modified Ashworth spasticity scale(MAS)muscle tone scores(P＜0.01),decreased expression of succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase at protein and mRNA levels,and increased expression of expression of glutamic acid decarboxylase 67 at protein and mRNA levels(P＜0.01);the neuronal cell structure was relatively intact,with only some irregular cavities visible and reduced nuclear consolidation.(2)Compared with the Chinese herbal prescription with head acupuncture exercise therapy group,the neurological deficit scores and MAS muscle tone scores were higher in the exercise therapy group(P＜0.05),and the MAS muscle tone scores were higher in the head-acupuncture group and the Chinese herbal prescription group(P＜0.05,P＜0.01),while the expressions of glutamic acid decarboxylase 67 protein and succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase mRNAs were increased in all the other intervention groups(P＜0.05,P＜0.01).Neuronal cells in the Chinese herbal prescription with head acupuncture exercise therapy group were more orderly arranged and clearly outlined,with less nuclear consolidation and shape irregularity compared with the other intervention groups.(3)The neurological deficit score and MAS muscle tone score in the Chinese herbal prescription with head acupuncture exercise therapy group were significantly lower after treatment(P＜0.01).To conclude,Yi'nao Fujian herbal prescription combined with head-acupuncture exercise therapy can improve post-stroke spasticity by affecting the expression of γ-aminobutyric acid transaminase in rats,which is more effective than Chinese herbal prescription alone,exercise therapy alone,and head-acupuncture alone.

BACKGROUND:Chinese herbal prescription with head acupuncture exercise therapy has significant clinical efficacy in the treatment of limb spasticity after ischemic stroke;however,the exact mechanism is not clear.OBJECTIVE:To explore the possible mechanism of the combination of Chinese herbal prescription with head acupuncture exercise therapy in improving limb spasticity after stroke.METHODS:Seventy Sprague-Dawley rats were divided into blank,model,exercise therapy,head-acupuncture,Chinese herbal prescription,Chinese herbal prescription with head acupuncture exercise therapy,and sham-operation groups using the random number method,with 10 rats in each group.Except for the blank group and the sham-operation group,a rat model of cerebral ischemia/reperfusion injury was made by using the middle cerebral artery cable embolism method in the rest of the groups.Interventions in each group started on the 3rd day after modeling.In the Chinese herbal prescription group,rats were given 1.5 g/kg Yi'nao Fujian herbal prescription by gavage;in the head acupuncture group,acupuncture was applied to Baihui and 2 mm on the left and right sides of Baihui,and was left in place for 30 minutes;in the exercise therapy group,rats were exercised on a treadmill for 30 minutes;in the Chinese herbal prescription with head acupuncture exercise therapy group,1.5 g/kg Yi'nao Fujian herbal prescription was given by gavage followed by acupuncture treatment(identical to that in the head acupuncture group,and then the animals were exercised for 30 minutes on the treadmill while the acupuncture needles remained in place.Rats in the model and sham-operation groups were subjected to grasping under the same environmental conditions and placed on a rat immobilizer for 30 minutes,and the blank group did not have any intervention.The frequency of intervention in each group was once a day for 7 consecutive days.The neurological deficit score and muscle tone were evaluated in each group before and after treatment.Pathological changes in rat brain tissue were observed.Protein and mRNA expressions of glutamic acid decarboxylase 67,succinate semialdehyde dehydrogenase,and γ-aminobutyric acid transaminase in the cerebral cortex of the rats were detected.RESULTS AND CONCLUSION:(1)Compared with the model group,the Chinese herbal prescription with head acupuncture exercise therapy group had lower neurological deficit scores and modified Ashworth spasticity scale(MAS)muscle tone scores(P＜0.01),decreased expression of succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase at protein and mRNA levels,and increased expression of expression of glutamic acid decarboxylase 67 at protein and mRNA levels(P＜0.01);the neuronal cell structure was relatively intact,with only some irregular cavities visible and reduced nuclear consolidation.(2)Compared with the Chinese herbal prescription with head acupuncture exercise therapy group,the neurological deficit scores and MAS muscle tone scores were higher in the exercise therapy group(P＜0.05),and the MAS muscle tone scores were higher in the head-acupuncture group and the Chinese herbal prescription group(P＜0.05,P＜0.01),while the expressions of glutamic acid decarboxylase 67 protein and succinate semialdehyde dehydrogenase andγ-aminobutyric acid transaminase mRNAs were increased in all the other intervention groups(P＜0.05,P＜0.01).Neuronal cells in the Chinese herbal prescription with head acupuncture exercise therapy group were more orderly arranged and clearly outlined,with less nuclear consolidation and shape irregularity compared with the other intervention groups.(3)The neurological deficit score and MAS muscle tone score in the Chinese herbal prescription with head acupuncture exercise therapy group were significantly lower after treatment(P＜0.01).To conclude,Yi'nao Fujian herbal prescription combined with head-acupuncture exercise therapy can improve post-stroke spasticity by affecting the expression of γ-aminobutyric acid transaminase in rats,which is more effective than Chinese herbal prescription alone,exercise therapy alone,and head-acupuncture alone.

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

Background::Ciprofol (HSK3486; Haisco Pharmaceutical Group Co., Ltd., Chengdu, China), developed as a novel 2,6-disubstituted phenol derivative showed similar tolerability and efficacy characteristics as propofol when applicated as continuous intravenous infusion for 12 h maintenance sedation in a previous phase 1 trial. The phase 2 trial was designed to investigate the safety, efficacy, and pharmacokinetic characteristics of ciprofol for sedation of patients undergoing mechanical ventilation.Methods::In this multicenter, open label, randomized, propofol positive-controlled, phase 2 trial, 39 Chinese intensive care unit patients receiving mechanical ventilation were enrolled and randomly assigned to a ciprofol or propofol group in a 2:1 ratio. The ciprofol infusion was started with a loading infusion of 0.1-0.2 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 0.30 mg·kg -1·h -1, which could be adjusted to an infusion rate of 0.06 to 0.80 mg·kg -1·h -1, whereas for propofol the loading infusion dose was 0.5-1.0 mg/kg for 0.5-5.0 min, followed by an initial maintenance infusion rate of 1.50 mg·kg -1·h -1, which could be adjusted to 0.30-4.00 mg·kg -1·h -1 to achieve -2 to +1 Richmond Agitation-Sedation Scale sedation within 6-24 h of drug administration. Results::Of the 39 enrolled patients, 36 completed the trial. The median (min, max) of the average time to sedation compliance values for ciprofol and propofol were 60.0 (52.6, 60.0) min and 60.0 (55.2, 60.0) min, with median difference of 0.00 (95% confidence interval: 0.00, 0.00). In total, 29 (74.4%) patients comprising 18 (69.2%) in the ciprofol and 11 (84.6%) in the propofol group experienced 86 treatment emergent adverse events (TEAEs), the majority being of severity grade 1 or 2. Drug- and sedation-related TEAEs were hypotension (7.7% vs. 23.1%, P = 0.310) and sinus bradycardia (3.8% vs. 7.7%, P = 1.000) in the ciprofol and propofol groups, respectively. The plasma concentration-time curves for ciprofol and propofol were similar. Conclusions::ciprofol is comparable to propofol with good tolerance and efficacy for sedation of Chinese intensive care unit patients undergoing mechanical ventilation in the present study setting.Trial registration::ClinicalTrials.gov, NCT04147416.

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Objective: To investigate the mediating effect of insomnia among mobile phone addiction, aggressive behaviors and self-perceived identity among university students. Methods: A total of 740 university students were sampled from five universities in Binjiang District, Hangzhou City using a cluster random sampling method. The mobile phone addiction, aggressive behaviors and self-perceived identity were assessed using the Mobile Phone Addiction Index Scale, the Athens Insomnia Scale, the Chinese college students' version of the Buss-Perry Aggression Questionnaire, and the Self-Perceived Identity Scale, and the mediating effect of insomnia among mobile phone addiction, aggressive behaviors and self-perceived identity was examined using Process macro program and Bootstrap method. Results: A total of 740 questionnaires were allocated, and 700 valid questionnaires were recovered, with an effective recovery rate of 94.59%. The respondents included 221 men (31.57%) and 479 women (68.43%), and there were 607 respondents with a specialty of medicine (86.71%). There were 331 participants detected with mobile phone addiction (47.29%), 90 with aggressive behaviors (12.86%) and 289 with low-level self-perceived identity (41.29%), and the prevalence rates of mild, moderate, severe and extremely severe insomnia were 28.00%, 26.14%, 26.43% and 19.43% among respondents, respectively. Mobile phone addiction had a direct predictive effect on aggressive behaviors (β=0.301, P<0.001) and self-perceived identity (β=-0.129, P<0.001), and presented an indirect predictive effect on aggressive behaviors (effect of mobile phone addiction on insomnia: β=0.083, P<0.001; effect of insomnia on aggressive behaviors: β=0.999, P<0.001; effect of insomnia on self-perceived identity: β=-0.698, P<0.001). The contributions of mediating effects caused by insomnia were 21.61% and 31.02% to total effects. Conclusions Insomnia presents partial mediating effects among mobile phone addiction, aggressive behaviors and self-perceived identity among university students. Mobile phone addiction may directly affect aggressive behaviors and self-perceived identity, and indirectly affect aggressive behaviors and self-perceived identity via insomnia.

Krüppel-like factors (KLFs) play extremely important roles in genesis and development of tumors. Simultaneously, KLFs have been proven to affect the proliferation, differentiation and migration of hepatocellular carcinoma cells. Nine members in the KLFs family (KLF2, KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF14 and KLF17) are involved in the occurrence and development of hepatocellular carcinoma in various ways as an oncogene and tumor suppressor gene. Therefore, the KLFs family will hopefully become biological therapeutic targets for hepatocellular carcinoma.

With the development of mass spectrometry technologies and bioinformatics analysis algorithms, disease research-driven human proteome project (HPP) is advancing rapidly. Protein biomarkers play critical roles in clinical applications and the biomarker discovery strategies and methods have become one of research hotspots. Feature selection and machine learning methods have good effects on solving the "dimensionality" and "sparsity" problems of proteomics data, which have been widely used in the discovery of protein biomarkers. Here, we systematically review the strategy of protein biomarker discovery and the frequently-used machine learning methods. Also, the review illustrates the prospects and limitations of deep learning in this field. It is aimed at providing a valuable reference for corresponding researchers.
Algorithms ; Biomarkers ; Humans ; Machine Learning ; Mass Spectrometry ; Proteomics

Tumor-specific gene mutations might generate suitable neoepitopes for cancer immunotherapy that are highly immunogenic and absent in normal tissues. The high heterogeneity of the tumor genome poses a big challenge for precision cancer immunotherapy. Mutations characteristic of each tumor can help to distinguish it from other tumors. Based on these mutations' characteristic, it is possible to develop immunotherapeutic strategies for specific tumors. In this study, a tumor neoantigen prediction scheme was proposed, in which both the intracellular antigen presentation process and the ability to bind with extracellular MHC molecule were taken into consideration. The overall design is meritorious and may help reduce the cost for validation experiments compared with conventional methods. This strategy was tested with several cancer genome datasets in the TCGA database, and a number of potential tumor neoantigens were predicted for each dataset. These predicted neoantigens showed tumor type specificity and were found in 20% to 70% of cancer patients. This scheme might prove useful clinically in future.
Antigens, Neoplasm ; Computational Biology ; Genome, Human ; Humans ; Immunotherapy ; Mutation ; Neoplasms

Objective To study the value of echocardiography in diagnosis of prenatal closure of fetal ductus arteriosus(FDA) and discuss its characteristics. Methods Two cases with prenatal closure and one case with constriction of the FDA were examined.The echocardiographic characteristics were analyzed and the literature was reviewed. Results Right atrial and ventricular dilatation and severe tricuspid valve insufficiency were observed. After timely delivery, impaired right ventricular function improved significantly. Conclusions Fetal echocardiography plays an important role in diagnosis of prenatal closure of the FDA.