[Abstract] The circular RNA (circRNA) is a class of endogenous expressed non-coding RNA that are formed by covalently closed cyclization through reverse splicing. In recent years, a variety of highly conserved and cell-type specific circRNA have been identified in eukaryotes. Alzheimer’ s disease (AD) is a common neurodegenerative disease and the most common cause of dementia in the elderly. Recent studies had shown that circRNA was involved in the pathogenesis and development of AD, such as amyloid β-protein (Aβ) metabolic, neuroinflammation, oxidative stress, autophagy and synaptic plasticity. The role and application value of circRNA in AD pathology are reviewed to provide a theoretical basis for the application of circRNA in the treatment and diagnosis of AD.

BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed. ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD. MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients. ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P<0.05］. A statistical difference was found in plasma G-CSF level ［63.92（54.60， 89.43）pg/mL vs. 47.80（33.41， 74.66）pg/mL vs. 71.47（61.20， 79.99）pg/mL， H=8.247， P=0.016］ and plasma M-CSF level ［20.05（16.05， 22.23）pg/mL vs. 13.05（11.43， 17.50）pg/mL vs. 18.95（14.59， 22.88）pg/mL， H=7.620， P=0.022］ among retardation group， non-retardation group and healthy control group. The post hoc pairwise comparisons using Bonferroni correction indicated that plasma G-CSF level was lower in non-retardation group compared with healthy control group （adjusted P<0.05）， and plasma M-CSF level was higher in retardation group compared with non-retardation group （adjusted P<0.05）. The retardation factor score in HAMD-17 was positively correlated with plasma M-CSF level in MDD patients （r=0.348， P<0.05）. ConclusionThe prevalence of psychomotor retardation in MDD patients may be related to abnormally elevated plasma M-CSF level. ［Funded by Shanghai "Science and Technology Innovation Action Plan" Project in Medical Innovation Research Field （number， 21Y11905600）； Shanghai "Science and Technology Innovation Action Plan" Project in Natural Science Field （number， 21ZR1455100）； Shanghai Mental Health Center Scientific Research Project （number， 2021-YJ02）］

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.
Bayes Theorem ; Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; Chemotherapy, Adjuvant ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.
China ; Drugs, Chinese Herbal ; Information Storage and Retrieval ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Quality Control

Through investigating the current research on the effect of Naoxintong Capsules in the treatment of cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris, this study conducted a clinical comprehensive evaluation in "6+1" dimensions [safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM)], so as to highlight the advantages and clinical value of Naoxintong Capsules. By combining qualitative and quantitative methods, we used the multi-criteria decision analysis(MCDA) model to measure each dimension, and the results thereby were divided into four grades of A, B, C, and D in high-to-low order. Through literature review and evaluation, the adverse effects of Naoxintong Capsules are mainly caused by the gastrointestinal system. Since the safety risk is controllable based on current research, the safety evaluation is grade B. The effectiveness of Naoxintong Capsules combined with conventional western medicine in the treatment of cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris is evaluated as grade A, as compared with conventional therapy alone. The economy of Naoxintong Capsules, compared with Tongxinluo Capsules, is assessed as grade B. According to literature reports, Naoxintong Capsules exhibits outstanding clinical innovation in optimizing the current anti-platelet therapy strategy for patients with coronary heart disease after percutaneous coronary intervention(PCI), and the innovation is class A. Given the capsule formulation is convenient for storage and transportation, and its usage is easy for patients to grasp and accept, the suitability is grade B. The accessibility is grade A considering the price level, availability, and affordability, and the characteristics of TCM are evaluated as grade A from the perspectives of theoretical characteristics and human experience. The results of the comprehensive drug evaluation showed that the clinical value of Naoxintong Capsules is class A for treating cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris. According to the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs(trial 2021 version) issued by the National Health Commission, relevant policy results for basic clinical drug management can be formulated directly by procedure.
Angina Pectoris ; Capsules ; Cerebral Infarction/drug therapy* ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Percutaneous Coronary Intervention ; Qi

In this study, Tabu search algorithm was used to analyze the drug combination of Xingnaojing Injection in the treatment of brain injury and complications in the real world, and the clinical drug combination of Xingnaojing Injection in the treatment of brain injury and complications was selected and summarized. The combination of Xingnaojing Injection, Namefen and Citicoline were recommended in the treatment of brain injury and complications. For brain edema and nerve injury, Mannitol/Glycerol Fructose/Furosemide+Tetrahexose Monosialate Ganglioside Sodium should be recommended. For those with pulmonary infection, Xingnaojing Injection+Xiyanping+Ambroxol Hydrochloride+Tanreqing Injection should be recommended. For those with shock, Hydroxyethyl Starch+Dopamine Hydrochloride/Dobutamine Hydrochloride+Sodium Bicarbonate should be recommended. The combination reflected the characteristics of Chinese and Western medicine. The above medication regimen was only for clinicians' reference. The clinical application should be based on patients' specific conditions, clinical benefits and risks, as well as the incompatibility. On the basis of the findings, further studies can be carried out for prospective clinical efficacy evaluation and safety evaluation for a specific subgroup module.
Algorithms ; Drugs, Chinese Herbal ; Humans ; Injections ; Medicine, Chinese Traditional ; Prospective Studies

In this study, Tabu search algorithm was used to analyze the effect of Xingnaojing Injection in the treatment of cerebral hemorrhage in the real world. Through the analysis of the results, the therapies based on the pathogeny of cerebral hemorrhage were screened out: Xingnaojing Injection+hemostatic drugs for promoting blood circulation and removing stasis. Cerebral hemorrhage complicated with brain edema: combined with mannitol or mannitol+aescin. The patients with relevant complications in the acute stage of cerebral hemorrhage could select according to the indications: ①Aminocycline+Oxiracetam+Piperacillin Sodium Sulbactam Sodium+Sodium Lactate Ringer; ②Aminocycline+Oxiracetam+Nifedipine+Captopril+Metoclopramide+Cimetidine; ③Insulin+Pantoprazole+So-dium Nitroprusside. The combined therapies for patients of the stable stage with complicating diseases could select according to the indications: ① Monosialotetrahexosyl Ganglioside Sodium+Deproteinized Calf Blood Serum+Nitroglycerin+Compound Potassium Dihydrogn Phosphate; ② Edaravone+Gangliosides+Captopril+Levofloxacin+Tanreqing Injection+Aminophylline. The analysis of subgroup module of drugs for promoting blood circulation and removing blood stasis suggested that the safety of traditional Chinese medicine should be paid attention to in the treatment of cerebral hemorrhage. This study was based on the data of the real world, but with some problems, such as lack of data and confounding factors. The summarized medication plan is only for the reference of clinicians. The clinical application shall be based on the specific situation of patients and the clinical benefits and risks, and pay attention to the incompatibility.
Algorithms ; Brain Edema ; Cerebral Hemorrhage ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional