Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

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*

AIM: To establish a HPLC-QqQ-MS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration. METHODS: The experiment established a high-sensitivity LC-MS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration C

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Hemostatics ; Quality Control ; Rats ; Rhizome ; Saponins

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Stomach pain in Chinese medicine (CM) is a very common disorder in clinical practice and it has been listed as one of the pilot three conditions in Hong Kong to develop evidence-based CM clinical practice guidelines (CM CPGs). The aim of this stomach Pain CPG is to summarize the treatment methods of stomach pain with CM and evaluate reasonably, then to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we defined stomach pain in CM and the category of chronic gastritis in Western medicine. The clinical manifestation, CM pattern classification, and CM intervention including herbal medicine treatment based on pattern differentiation, symptomatic treatment, acupuncture treatment, regulation and nursing were illustrated.

Surgical operation in treating obesity and type 2 diabetes is popularizing rapidly in China. Correct prevention and recognition of perioperation-related operative complications is the premise of ensuring surgical safety. Familiar complications of the operation include deep venous thrombosis, pulmonary artery embolism, anastomotic bleeding, anastomotic fistula and marginal ulcer. The prevention of deep venous thrombosis is better than treatment. The concrete measures contain physical prophylaxis (graduated compression stocking and intermittent pneumatic compression leg sleeves) and drug prophylaxis (unfractionated heparin and low molecular heparin), and the treatment is mainly thrombolysis or operative thrombectomy. The treatment of pulmonary artery embolism includes remittance of pulmonary arterial hypertension, anticoagulation, thrombolysis, operative thrombectomy, interventional therapy and extracorporeal membrane oxygenation (ECMO). Hemorrhage is a rarely occurred but relatively serious complication after bariatric surgery. The primary cause of anastomotic bleeding after laparoscopic gastric bypass is incomplete hemostasis or weak laparoscopic repair. The common bleeding site in laparoscopic sleeve gastrectomy is gastric stump and close to partes pylorica, and the bleeding may be induced by malformation and weak repair technique. Patients with hemodynamic instability caused by active bleeding or excessive bleeding should timely received surgical treatment. Anastomotic fistula in gastric bypass can be divided into gastrointestinal anastomotic fistula and jejunum-jejunum anastomotic fistula. The treatment of postoperative anastomotic fistula should vary with each individual, and conservative treatment or operative treatment should be adopted. Anastomotic stenosis is mainly related to the operative techniques. Stenosis after sleeve gastrectomy often occurs in gastric angle, and the treatment methods include balloon dilatation and stent implantation, and surgical treatment should be performed when necessary. Marginal ulcer after gastric bypass is a kind of peptic ulcer occurring close to small intestine mucosa in the junction point of stomach and jejunum. Ulcer will also occur in the vestige stomach after laparoscopic sleeve gastrectomy, and the occurrence site locates mostly in the gastric antrum incisal margin. Preoperative anti-HP (helicobacter pylorus) therapy and postoperative continuous administration of proton pump inhibitor (PPI) for six months is the main means to prevent and treat marginal ulcer. For patients on whom conservative treatment is invalid, endoscopic repair or surgical repair should be considered. Different surgical procedures will generate different related operative complications. Fully understanding and effectively dealing with the complications of various surgical procedures through multidisciplinary cooperation is a guarantee for successful operation.
Anastomosis, Surgical ; adverse effects ; Anticoagulants ; therapeutic use ; Bariatric Surgery ; adverse effects ; Catheterization ; China ; Conservative Treatment ; Constriction, Pathologic ; etiology ; therapy ; Digestive System Fistula ; etiology ; therapy ; Endoscopy, Gastrointestinal ; methods ; Extracorporeal Membrane Oxygenation ; Gastrectomy ; adverse effects ; Gastric Bypass ; adverse effects ; Gastric Mucosa ; pathology ; Gastric Stump ; physiopathology ; surgery ; Gastrointestinal Hemorrhage ; etiology ; prevention & control ; surgery ; Hemostasis, Surgical ; adverse effects ; methods ; Hemostatic Techniques ; Heparin ; therapeutic use ; Humans ; Intermittent Pneumatic Compression Devices ; Intestine, Small ; pathology ; Laparoscopy ; adverse effects ; Margins of Excision ; Peptic Ulcer ; etiology ; therapy ; Postoperative Complications ; diagnosis ; prevention & control ; therapy ; Pulmonary Embolism ; etiology ; therapy ; Stents ; Stockings, Compression ; Thrombectomy ; Thrombolytic Therapy ; Venous Thrombosis ; etiology ; prevention & control ; therapy

OBJECTIVETo examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells.

METHODSNeuronal cells (primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin (Rap) or N-acetyl-L-cysteine (NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3'-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays.

RESULTSCd-induced activation of Akt/mTOR signaling, including Akt, mTOR, p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein (Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G).

CONCLUSIONCd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.

Animals ; Apoptosis ; drug effects ; Cadmium ; toxicity ; Caspases ; metabolism ; Mitochondria ; drug effects ; Neurons ; drug effects ; PC12 Cells ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism

OBJECTIVETo systematically review the clinical practice guidelines (CPGs) for ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.

METHODSCM CPGs for ischemic stroke were searched in 5 online databases and hand-searches in CPGrelated handbooks published from January 1990 to December 2012. The CPGs were categorized into evidence based (EB) guideline, consensus based with no explicit consideration of evidence based (CB-EB) guideline and consensus based (CB) guideline according to the development method. Three reviewers independently appraised the CPGs based on AGREE II instrument, and compared the CPGs' recommendations on CM pattern classification and treatment.

RESULTSFive CM CPGs for ischemic stroke were identified and included. Among them, one CPG was EB guideline, two were CB guidelines and two were CB-EB guidelines. The quality score of the EB guideline was higher than those of the CB-EB and CB guidelines. Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive protocol of integrative Chinese and Western medicine recommended in the EB CPG was mostly recommended for ischemic stroke in the CPGs. The recommendations varied based on the CM patterns.

CONCLUSIONThe quality of EB CPG was higher than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative approaches were included in CPGs as major interventions.

Biomedical Research ; Brain Ischemia ; complications ; therapy ; Health Planning Guidelines ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic ; Stroke ; complications ; therapy

OBJECTIVE: To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism. METHODS: Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism. RESULTS: (1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group. CONCLUSION Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.
Acetylcholine/metabolism* ; Alcohols/pharmacology* ; Animals ; Brain/physiopathology* ; Drug Synergism ; Ketamine/pharmacology* ; Male ; Maze Learning/drug effects* ; Memory/drug effects* ; Memory Disorders/physiopathology* ; Mice ; Mice, Inbred ICR ; Serotonin/metabolism* ; Spatial Behavior/drug effects*