Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats ; Animals ; Mitophagy ; Alzheimer Disease/genetics* ; Powders ; Protein Kinases/metabolism* ; Ubiquitin-Protein Ligases/metabolism*

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC₅₀) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.
Animals ; Zebrafish/metabolism* ; Embryo, Nonmammalian/metabolism* ; Transcriptome ; Oxidative Stress ; Water Pollutants, Chemical/metabolism*

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4
Animals ; Azoxymethane/toxicity* ; CD8-Positive T-Lymphocytes ; Colitis/genetics* ; Dextran Sulfate/toxicity* ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Glycogen Synthase Kinase 3 beta ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Wnt Signaling Pathway/drug effects*

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to this study to detect heavy metal contents in Coptidis Rhizoma from different habitats, for a comprehensive understanding of heavy metal residues in Coptidis Rhizoma. Decocting method and artificial gastrointestinal digestion model were used to determine transfer rates of heavy metals in assessment of health risk of heavy metals using the target hazard quotient (THQ) developed by the US EPA (1989). The results showed that excess rates of Cu, Pb, As, Cd and Hg of 17 batches of Coptidis Rhizoma were 0, 12%, 0, 0 and 0, respectively, under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metal. The transfer rates of Cu, Pb, As, Cd and Hg were 3.63%, 1.69%, 37.17%, 20.86% and 0 in decoction solution, respectively, and 59.15%, 29.98%, 67.55%, 104.59% and 0 in artificial gastrointestinal solution, respectively. The values of THQ under the two ways of administration in adults and children were 0.001 0, 0.005 3 and 0.000 7, 0.003 6, respectively, and the maximum residue limits (MRL) of heavy metals in Coptidis Rhizoma were higher than the contents of samples in this study. The research showed that the contents of heavy metals in Coptidis Rhizoma were in the safe ranges with no obvious risks to human body, indicating that the excessive of heavy metals in Coptidis Rhizoma might be attributed to the unduly strict standard. The contents of heavy metals in Coptidis Rhizoma of different habitats was estimated for health risks using international risk assessment model, which provides a reference for establishment of heavy metal standards in Coptidis Rhizoma.

Objective To investigate the expression of non receptor protein tyrosine phosphatase 12 (PTPN12) in hepatocellular carcinoma (HCC) and its adjacent tissues and investigate the relationship between the expression of non receptor protein and prognosis of hepatocellular carcinoma (HCC).Methods The expresson of PTPN12 protein in HCC tissues and adjacent liver tissues was detected by immunohistochemistry.The relationship between the expression of PTPN12 protein and prognosis of primary hepatocellular carcinoma was evaluated by rank correlation and Cox proportional hazards regression model.Results Compared with the adjacent liver tissues,the expression of PTPN12 protein in HCC tissues was significantly lower (55.83％ vs 43.12％,P＜0.005).Further analysis showed that the decreased expression of PTPN12 was closely related with tumor recurrence (x2 =4.346,P=0.015).Single factor analysis showed that the decreased expression of PTPN12 in hepatocellular carcinoma and liver cancer specific survival and recurrence of hepatocellular carcinoma related (x2=5.687,P＜0.001),and multivariate Cox proportional hazards regression model analysis showed that the expression of PTPN12 in patients with liver cancer were independent prognostic factors (x2 =6.687,P＜0.05).Conclusion The expression of PTPN12 protein was down or absent in human hepatocellular carcinoma,and the expression of PTPN12 may be a biomarker for the recurrence and prognosis of HCC patients.

Objective It is rarely reported whether myricetin inhibits the activation and function of cardiac fibroblasts and thereby prevents myocardial fibrosis. This study was to investigate the effects of myricetin on the activation,proliferation and secretion of cardiac fibroblasts and its possible molecular mechanisms. Methods Fibroblasts isolated from 1-3 days old rats were cultured and their activation,proliferation and secretion were induced with the transforming growth factor (TGF). The fibroblasts were incubated with myricetin at different concentrations of 1,3,10,30 and 100 μmol/L for 24 hours followed by detection of their proliferation with the CKK8 kit,the transcription levels of fibrotic factors by RT-PCR and the expression levels of α-SMA and signal proteins by immunoflu-orescence staining and Western blot,respectively. Results The expression of α-SMA was significantly up-regulated in the cardiac fi- broblasts of the rats in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups as compared with that in the control group (P<0.05) but down-regulated in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups in com-parison with that in the TGF-β group (P<0.05). At 48 hours,the transcription levels of collagenⅠ,collagenⅢ,fibronectin and con-nective tissue growth factor were markedly higher in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the control group (P<0.05) but lower in the 30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups than in the TGF-β group (P<0.05). The phosphorylation levels of smad2 and smad3 were remarkably elevated in the TGF-β,30 μmol/L myricetin+TGF-β and 100 μmol/L myricetin+TGF-β groups and the expression of smad4 reduced in the TGF-β group as com-pared with the control group (P<0.05). The levels of smad2,smad3 and smad4 were all significantly decreased in the 30 μmol/L myr-icetin+TGF-β and the 100 μmol/L myricetin+TGF-β groups in comparison with the TGF-β group (P<0.05). Conclusion Myricetin suppresses the activation,proliferation and secretion of cardiac fibroblasts induced by TGF-β via inhibiting the smad signaling pathway.

BACKGROUNDPatients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.

METHODSParticipants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.

RESULTSIn total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.

CONCLUSIONSHemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Adult ; Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Dialysis ; adverse effects ; mortality ; Retrospective Studies ; Risk Factors