OBJECTIVE: To explore the expression and function of microRNA-144 (miR-144) in β-thalassemia (β-thal). METHODS: The expression of miR-144 during the differentiation of murine erythroleukemia (MEL) cells and mouse embryonic liver-derived erythroid precursor cells was analyzed by real-time fluorescence quantitative PCR (qRT-PCR); The expression levels of miR-144 in peripheral blood and day-14.5 embryonic hepatocytes of wild-type (WT) and β-thal mice, as well as the expression levels of miR-144 in peripheral blood of β-thal patients, was also measured by qRT-PCR. The proportion of Ter119 and CD71 double positive cells in peripheral blood of mild and severe β-thal mice was analyzed by flow cytometry, and the expression levels of miR-144 in the peripheral blood of mild and severe β-thal mice and patients were compared; Bone marrow nucleated erythrocytes from WT mice and β-thal mice were sorted and the expression levels of miR-144 potential target genes were analyzed by gene chip. RESULTS: The expression levels of miR-144 were gradually increased during the directed differentiation of mouse MEL cells and embryonic hepatocytes to the erythroid lineage (r _MEL=0.97, r _{embryonic hepatocytes}=0.86); Compared with WT mice, the expression levels of miR-144 in peripheral blood and 14.5-day embryonic hepatocytes of β-thal mice were significantly increased (P < 0.05); Compared with healthy controls, the patients with β-thal showed an increased expression levels of miR-144 in peripheral blood (P < 0.05). Compared with mice and humans with mild β-thal, the expression levels of miR-144 in peripheral blood of those with severe β-thal were significantly increased (P < 0.05). The expressions of potential target genes of miR-144 in nucleated erythroid cells of the β-thal mice were significantly reduced compared to the WT group. CONCLUSION The expression level of miR-144 gradually increases in erythroid development, and compared with mild β-thal patients, the expression level of miR-144 in the peripheral blood is higher in severe β-thal patients. MiR-144 is expected to be an auxiliary diagnostic indicator for β-thal in clinical practice.
MicroRNAs/metabolism* ; beta-Thalassemia/genetics* ; Animals ; Mice ; Humans ; Cell Differentiation ; Hepatocytes

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Adenocarcinoma, Mucinous/therapy* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Appendiceal Neoplasms/surgery* ; Colorectal Neoplasms/pathology* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods* ; Female ; Humans ; Hyperthermia, Induced/methods* ; Male ; Middle Aged ; Peritoneal Neoplasms/secondary* ; Retrospective Studies ; Survival Rate

OBJECTIVES: To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits. METHODS: The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO₂) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS. RESULTS: The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung. CONCLUSIONS The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.
Animals ; Rabbits ; Carbofuran ; Chromatography, Liquid ; Postmortem Changes ; Tandem Mass Spectrometry ; Autopsy

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Cancer, Regional Perfusion ; Colorectal Neoplasms/therapy* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures ; Humans ; Hyperthermia, Induced ; Hyperthermic Intraperitoneal Chemotherapy ; Peritoneal Neoplasms/drug therapy* ; Prognosis ; Randomized Controlled Trials as Topic ; Survival Rate

This study aimed to explore the rule of Tibetan medicine in clinical treatment of hypertension( k Hrag-rLung-stod-vtshangs) and analyze the characteristics of its prescriptions. One hundred and thirty-seven cases of hypertension treated Tibetan medicine were collected. Data mining,Gephi,Cytoscape and other methods and software were used to analyze the characteristics of Tibetan medicine. The results showed that there were 44 cases of r Lung-type hypertension in clinical medical records,while 57 cases of k Hrag-type hypertension. There were 103 treatment prescriptions. The frequency of these prescriptions covered Twenty-five Yuganzi Pills( 96 times),Seventy Pearl Pills( 80 times),Eight Chenxiang Pills( 75 times),and Sanwei Ganlu Powder( 62 times),and they were highly correlated,with confidence greater than 95%. There were 332 prescriptions involved in the prescriptions which is core prescription medicines. This study first proposed the dosage analysis method of Tibetan medicine prescription medicines,and obtained the more dosage of Chebulae Fructus,Phyllanthi Fructus,Aucklandiae Radix,Aquilariae Lignum Resinatum and so on. The correlation analysis of the prescription medicines found that Carthami Flos,Myristicae Semen,Bambusae Concretio Silicea,Caryophylli Flos,Amomi Fructus Rotundus led by Tsaoko Fructus had a high correlation and a confidence greater than 75%. These herbs were guaranteed when Tibetan medicine was used in combination. The key drugs for protecting viscera and regulating the three gastric fires. The prescription is mainly cold,blunt,sparse and rough. Its efficacy focuses on the pathogenesis of blood fever,blood stickiness and venous blockage caused by heat,sharpness,odor and stickiness. It mainly treats Tibetan medicine diseases such as k Hrag-r Lung-stod-vtshangs and k Hrag-vpel( polyemia). It is suggested that Tibetan medicine has a three-in-one invisible treatment principle of " clearing blood-heat,opening vessel and regulating stomach-fire" in the treatment of hypertension,which attributed to both cardiovascular function and gastrointestinal metabolic function. This may be a significant and invisible knowledge of Tibetan medicine in the treatment of hypertension.
Data Mining ; Humans ; Hypertension ; drug therapy ; Medical Records ; Medicine, Tibetan Traditional ; Software

BACKGROUNDDendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis.

METHODSBone marrow-derived dendritic cells were obtained from C57BL/6 mice. One short-interfering RNA specific for MMP-13 was used to transfect DCs. MMP-13-silenced DCs and control DCs were prepared, and apoptosis was measured using real-time polymerase chain reaction and Western blotting. MMP-13-silenced DCs and control DCs were analyzed for surface expression of CD80 and CD86 and phagocytosis capability using flow cytometry.

RESULTSCompared to the control DCs, MMP-13-silenced DCs increased expression of anti-apoptosis-related genes, BAG1 (control group vs. MMP-13-silenced group: 4.08 ± 0.60 vs. 6.11 ± 0.87, P = 0.008), BCL-2 (control group vs. MMP-13-silenced group: 7.54 ± 0.76 vs. 9.54 ± 1.29, P = 0.036), and TP73 (control group vs. MMP-13-silenced group: 4.33 ± 0.29 vs. 5.60 ± 0.32, P = 0.001) and decreased apoptosis-related genes, CASP1 (control group vs. MMP-13-silenced group: 3.79 ± 0.67 vs. 2.54 ± 0.39, P = 0.019), LTBR (control group vs. MMP-13-silenced group: 9.23 ± 1.25 vs. 6.24 ± 1.15, P = 0.012), and CASP4 (control group vs. MMP-13-silenced group: 2.07 ± 0.56 vs. 0.35 ± 0.35, P = 0.002). Protein levels confirmed the same expression pattern. MMP-13-silenced groups decreased expression of CD86 on DCs; however, there was no statistical difference in CD80 surface expression. Furthermore, MMP-13-silenced groups exhibited weaker phagocytosis capability.

CONCLUSIONThese results indicate that MMP-13 inhibition dampens DC maturation, apoptosis, and phagocytosis.

Animals ; Apoptosis ; drug effects ; physiology ; Bone Marrow Cells ; cytology ; Dendritic Cells ; cytology ; drug effects ; metabolism ; Female ; Lipopolysaccharides ; pharmacology ; Matrix Metalloproteinase 13 ; metabolism ; physiology ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering

BACKGROUNDLhasa is the main residence of Tibetans and one of the highest cities in the world. Its unique geography and ethnic population provide the chance to investigate the interactions among high altitude, ethnicity, and cardiac adaptation. Meanwhile, echocardiographic data about healthy Tibetans on a large scale are not available. This study aimed to analyze physiological factors related to ventricular size and valvular function in healthy Tibetans in Lhasa.

METHODSA representative sample of residents in Tibet was recruited using a multistage cluster random sampling method. Two-dimensional echocardiographic measurements and Doppler evaluation for valvular function were performed. Healthy Tibetans in Lhasa constituted the study population. Associations between physiological parameters and ventricular dimensions in healthy Tibetans were analyzed by canonical correlation analysis. Factors related to valvular regurgitations were determined by logistic regression analysis.

RESULTSThe 454 healthy Tibetans (340 females and 114 male) in Lhasa were included in the final analysis. Canonical correlation analysis revealed that weight was positively correlated with the proximal right ventricular outflow diameter and the basal left ventricular linear dimension in both genders. Weight and pulse were negatively related to mild tricuspid regurgitation. Age was a positive factor for pulmonary and aortic regurgitations. The same was found between systolic blood pressure and mitral regurgitation.

CONCLUSIONSWeight is associated with ventricular size and valvular regurgitation in healthy Tibetans. It should be of more concern in research of high altitude population.

Background: Lhasa is the main residence of Tibetans and one of the highest cities in the world. Its unique geography and ethnic population provide the chance to investigate the interactions among high altitude, ethnicity, and cardiac adaptation. Meanwhile, echocardiographic data about healthy Tibetans on a large scale are not available. This study aimed to analyze physiological factors related to ventricular size and valvular function in healthy Tibetans in Lhasa. Methods: A representative sample of residents in Tibet was recruited using a multistage cluster random sampling method. Two?dimensional echocardiographic measurements and Doppler evaluation for valvular function were performed. Healthy Tibetans in Lhasa constituted the study population. Associations between physiological parameters and ventricular dimensions in healthy Tibetans were analyzed by canonical correlation analysis. Factors related to valvular regurgitations were determined by logistic regression analysis. Results: The 454 healthy Tibetans (340 females and 114 male) in Lhasa were included in the final analysis. Canonical correlation analysis revealed that weight was positively correlated with the proximal right ventricular outflow diameter and the basal left ventricular linear dimension in both genders. Weight and pulse were negatively related to mild tricuspid regurgitation. Age was a positive factor for pulmonary and aortic regurgitations. The same was found between systolic blood pressure and mitral regurgitation. Conclusions: Weight is associated with ventricular size and valvular regurgitation in healthy Tibetans. It should be of more concern in research of high altitude population.