Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

ObjectiveTo understand the physical development level of 3-7 years old children in Zhag′yab， and to provide reference for local health decision-making. MethodsA cross-sectional study was conducted between June 2021 and July 2021， with a sample of 1 247 Tibetan children aged 3-7 years from kindergartens in 13 districts of Zhag′yab. Their height and weight were measured and the hemoglobin was detected by a unified method. Standard statistical method was adopted （Z-score method）. Z-scores of length /height-for-age （HAZ）， Z-scores of weight-for-age （WAZ）， Z-scores of body mass index （BMI）-for-age （BAZ） and Z-scores of weight-for-height （WHZ） were calculated by WHO Anthro v3.2.2 and WHO Anthro Plus. The nutritional status of children was evaluated according to WHO diagnostic criteria for malnutrition and anemia. ResultsThe average WAZ and HAZ of children aged 3 to 7 in Zhag′yab were lower than the WHO standards，except for the WAZ of 4-year old， the differences were statistically significant （P<0.05）. The overall detection rate of malnutrition was 25.7%， stunting， underweight， wasting， overweight， obesity and anemia were 11.6%， 11.8%， 10.8%， 3.3%， 1.8% and 29.3%， respectively. The detection rates of all indicators in boys were higher than those in girls， and the differences were not statistically significant （P>0.05）. The overweight rate and obesity rate of rural children were lower than those of urban children， and the other detection rates were higher than those of urban children. The differences of underweight rate， obesity rate and anemia rate were statistically significant between urban and rural children （P<0.05）. Among the detection rates of all indicators in different age groups， there were statistically significant differences in the overweight rate and the anemia rate （P<0.05）. The overweight rate of children aged 4 and the anemia rate of children aged 5 were the highest. ConclusionsThe physical development of children aged 3 to 7 in Zhag′yab is poor， and the prevalence of malnutrition and anemia is high. Underweight and anemia are more serious in rural children， and the overweight and obesity problem of urban children is emerging. More attention should be paid to promote their nutritional status. The prevention and intervention of children’s malnutrition should be strengthened in Zhag′yab.

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
Antiviral Agents ; chemistry ; therapeutic use ; Betacoronavirus ; chemistry ; enzymology ; Coronavirus Infections ; drug therapy ; prevention & control ; virology ; Cysteine Endopeptidases ; chemistry ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Mass Spectrometry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; prevention & control ; Pneumonia, Viral ; drug therapy ; prevention & control ; virology ; Protein Interaction Maps ; Viral Nonstructural Proteins ; chemistry

Objective To study the reliability of Gleason score by prostate biopsy with prostatic cancer(PCa)in prediction of tumor location and analyse related influencing factors of positive surgical margins after radical prostatectomy.Methods The retrospective study recruited 72 patients with PCa who had been diagnosed by trans rectal ultrasound-guided prostate biopsy,and eventually treated with laparoscopic radical prostatectomy.The correlation of each index were analyzed by statistical software.Results In this study,Kappa test indicated a good agreement that Gleason score between prostate biopsy and radical prostatectomy.Biopsy positive more focused on four peripheral points near the bottom.Biopsy tumor location was not suitable for predicting tumor distribution.Biopsy Gleason score and biopsy positive percentage in biopsy specimen were independent predictors of positive surgical margins.F and L points had good correlation with the positive surgical margins.Conclusion The biopsy Gleason score is a good evidence to pathological grading in patients.These information will lead to positive surgical margins rise possibly:needle biopsy Gleason score exceed 7.25,positive biopsy percentage more than 45% and the location positive biopsy close to prostate apex.

According to the latest data from the National Cancer Center of China, prostate cancer (PCa) has become the highest incidence tumors of urinary since 2008, and its incidence and mortality has occupied great attention in the past decades. Therefore, the choice of safe and effective diagnostic method, to detect the occurrence of PCa, is necessary. The way of clinical diagnosis mainly includes digital rectal examination, serum PSA, transrectal ultrasound, MRI spectroscopy imaging, and prostate biopsy, ect. Prostate biopsy is the most reliable diagnosis method and agold standardfor the diagnosis of PCa. The systematic use of the prostate biopsy has greatly improved the diagnosis of PCa. However, there are several prostate biopsy scheme and scholars proposed a variety of programs on the choice of puncture point. It has not yet formed a standard method at this stage. In this study, we will review the development of prostate biopsy and the status recent research to explore application value of different method.

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*

OBJECTIVE: To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism. METHODS: PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting. RESULTS: For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations. CONCLUSION Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.
Anesthetics, Dissociative/pharmacology* ; Animals ; Apoptosis/drug effects* ; Blotting, Western ; Cell Proliferation/drug effects* ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation/drug effects* ; Ketamine/pharmacology* ; PC12 Cells ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Time Factors ; bcl-2-Associated X Protein/metabolism*

OBJECTIVE: To observe the symptoms similar to schizophrenia in mice after ketamine single or continuous injection and to evaluate the feasibility of schizophrenia model injected with different dose of ketamine. METHODS: A total of 40 male mice were randomly divided into 4 groups, which were injected intraperitoneally with physiological saline (control group), 25 mg/kg ketamine (low dose group), 50 mg/kg ketamine (middle dose group), and 100 mg/kg ketamine (high dose group) qd for 7 days continuously. The behavior changes of mice were observed. RESULTS: Hyperactivity, stereotyped behavior and ataxia (P < 0.01) were observed in high dose group after single injection. After continuous injection of ketamine for 7 days, the middle dose group showed hyperactivity, stereotyped behavior and ataxia (P < 0.05), stereotyped behavior and ataxia were more significant in high dose group (P < 0.01). CONCLUSION Ketamine can induce the symptoms similar to schizophrenia in mice after single or continuous injection. The symptoms induced by high dose ketamine will be more prominent and stable after continuous injection.
Animals ; Ataxia/pathology* ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Forensic Psychiatry ; Injections, Intraperitoneal ; Ketamine/administration & dosage* ; Male ; Mice ; Motor Activity/drug effects* ; Random Allocation ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Schizophrenia/pathology* ; Stereotyped Behavior/drug effects*

OBJECTIVE: To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia. METHODS: Fifty KM mice were randomly divided into 5 groups which were administered intraperitoneally with saline, clozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage (25 mg/kg), middle dosage (50 mg/kg) and high dosage (100 mg/kg) one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the clozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline. CONCLUSION Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.
Animals ; Clozapine/therapeutic use* ; Disease Models, Animal ; Dose-Response Relationship, Drug ; ErbB Receptors/metabolism* ; Hippocampus/pathology* ; Ketamine/adverse effects* ; Male ; Mice ; Neuregulin-1/metabolism* ; Neurons/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Receptor, ErbB-4 ; Reverse Transcriptase Polymerase Chain Reaction ; Schizophrenia/genetics*

OBJECTIVETo explore the efficacy of KGQG and its therapeutic mechanisms in chronic hepatitis B patients with liver fibrosis.

METHODS57 chronic hepatitis B patients with liver fibrosis were randomly divided into two groups: 45 cases in KGQG group were treated by KGQG and routine medications; 12 cases in control group were treated by routine medications only. Serum liver function test results, PCIII, CIV, HA and liver biopsy results of these 57 patients were simultaneously collected and analyzed before and after this intervention.

RESULTSKGQG group showed better efficacy over control group in liver function recovery, decrease of serum PCIII, CIV, HA levels and liver pathologic grades (P 0.05 or 0.01).

CONCLUSIONThe KGQG could effectively ameliorate liver function and facilitate the inhibition and degradation of liver fibrosis in chronic hepatitis B patients, which may be developed as a novel therapeusis to treat this hard-to-cure disease.

Adolescent ; Adult ; Collagen Type IV ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; pathology ; physiopathology ; Humans ; Immunohistochemistry ; Liver Cirrhosis ; drug therapy ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged