ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Objective To analyze the literature related to diphenidol tablets poisoning,the characteristics of poisoning were summarized to provide reference for controlling the suicidal abuse risk of diphenidol tablets.Methods The global literature on suicide,overdose,poisoning,shock,and death related to difenidol published from January 1,2011 to December 31,2022 was analyzed,including gender,age,dosage,cardiac(blood)concentration,poisoning symptoms,etc.Results Young women were the majority of people with poisoning.The highest proportion of the age group is 11 to 30 years group.Patients who take medication doses greater than 3 000 mg may have a higher risk of death;patients with a heart(blood)concentration greater than 6 μg·mL-1 may have a higher risk of death.Malignant arrhythmia,consciousness disorders,coma,and apnea are common serious adverse events during poisoning.Conclusion It is recommended that the drug regulatory authorities should require the Listing permit holder of difenidol tablets to add the risk and symptoms of poisoning into the instructions.It is suggested that restricting individual consumers from purchasing large amounts of difenidol tablets in the short term.It is recommended that canceling the high-dose sales packaging of difenidol tablets.It is suggested that converting difenidol tablets into prescription drugs,even consider canceling the registration certificate of difenidol tablets.

Objective To explore the efficacy of pancreatic kallidinogenase enteric-coated tablet combined with irbesartan tablet in the treatment of elderly patients with type 2 diabetic nephropathy(DN).Methods Elderly patients with type 2 DN were selected as the research subjects,and were randomized into control group and treatment group.The control group was given 150 mg of irbesartan tablets once a day,while the treatment group was given 240 U of pancreatic kallidinogenase enteric-coated tablets three times a day on the basis of the control group.The clinical efficacy,renal function indicators[serum creatinine(SCr),blood urea nitrogen(BUN),urinary albumin excretion rate(UAER)],hemodynamic indicators[fibrinogen(FIB),whole blood viscosity,hematocrit(HCT)],microvascular lesion indicators[vascular endothelial growth factor(VEGF),soluble intercellular adhesion molecule-1(sICAM-1)],B-ultrasound detection indicators[maximum aortic flow velocity(Vmax),minimum diastolic flow velocity(Vmin),resistance index(RI)at the renal hilum]before and after treatment and adverse drug reactions were compared between both groups.Results After treatment,the total effective rates in control group and treatment group were 85.42％and 97.92;SCr levels were(90.47±18.14)and(80.28±12.04)μmol·L-1;BUN levels were(7.24±1.34)and(6.54±1.21)mmol·L-1;UAER levels were(36.17±6.07)and(31.04±5.21)μg·min-1;FIB levels were(4.32±0.59)and(3.95±0.48)g·L-1;whole blood viscosity values were(7.38±1.15)and(6.81±0.98)mPa·s;HCT levels were(38.63±7.01)％and(36.17±6.48)％;VEGF levels were(254.18±45.59)and(212.14±40.48)pg·mL-1;human sICAM-1 levels were(336.40±61.57)and(295.30±58.46)pg·L-1;the Vmax of renal artery were(72.58±3.60)and(74.98±3.78)cm·s-1;the Vmin values were(22.48±3.14)and(24.83±3.63)cm·s-1;the RI values were 0.73±0.06 and 0.68±0.07,respectively.There were statistical differences in the above indicators between control group and treatment group(all P＜0.05).The total incidence eares of adverse drug reactions in control group and treatment group were 4.17％(2 cases/48 cases)and 8.33％(4 cases/48 cases)respectively(P＞0.05).Conclusion Pancreatic kallidinogenase enteric-coated tablet combined with irbesartan tablet can effectively improve the renal function of elderly patients with type 2 DN,improve the blood flow and delay microvascular lesion,and enhance the efficacy,therefore it is safe and effective.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Kashin-Beck disease (KBD) is a chronic endemic bone and joint disease, with severe cases of short stature, joint deformities, and significantly reduced quality of life. Its etiology is currently unclear. Matrix metalloproteinases (MMPs) are endopeptidases that can degrade the extracellular matrix of articular cartilage cells, and are closely related to the occurrence and development of bone and joint diseases. At present, some scholars have found that MMPs can cause cartilage damage in KBD patients and promote the progression of KBD, but its specific mechanism of action is still unclear. This article reviews the research progress on the etiology of KBD, MMPs and its related genes, and their relationship with KBD cartilage injury both domestically and internationally. In order to provide theoretical support for in-depth research on the pathogenesis of KBD and to improve and update its treatment methods.

Objective To investigate the advantages and efficacy of traction with titanium clips in endoscopic submucosal dissection(ESD)for large laterally spreading tumor(LST)in rectum and sigmoid colon.Methods 67 patients with large sigmoid or rectal LST underwent ESD from January 2018 to June 2022 were analyzed retrospectively,including 32 patients in Group A and 35 patients in Group B.Group A was treated with clip-line traction and group B was treated with traditional ESD.The size of lesion,the total operation time,the submucosal dissection time,submucosal dissection rate,submucosal injection number,en bloc resection rate,R0 resection rate,curative resection rate and complications of the two groups were compared.Results LST-G-M was the most common type and villous adenoma was the main pathology in both groups.There were no differences in en bloc resection rate,R0 resection rate and incidence of complications between the two groups.The average size of group A was(13.6±8.4)cm2,significantly larger than that in group B(9.3±4.7)cm2,the total operation time was(42.3±10.3)min in group A,significantly shorter than that in group B(47.9±10.1)min,submucosal dissection time was(30.7±8.2)min in group A,significantly shorter than that in group B(36.1±7.6)min,submucosal injection number was(2.7±1.1)times in group A,significantly less than that in group B(3.5±1.2)times,submucosal dissection rate was(0.4±0.2)cm2/min in group A,significantly faster than that in group B(0.2±0.1)cm2/min,the differences were statistically significant(P<0.05).Conclusion Compared with traditional ESD,clip-line traction can provide a better surgical field and more effective dissection for large LST in rectum and sigmoid colon.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

ObjectiveTo investigate the value of the serum levels of Clusterin and sphingosine 1-phosphate （S1P） in assessing the prognosis of sepsis patients with acute liver injury. MethodsA total of 127 sepsis patients with acute liver injury who were admitted to Lianyungang Hospital， Xuzhou Medical University， from March 2019 to May 2022 were enrolled， and according to their prognosis after 28 days of treatment， they were divided into death group with 35 patients and survival group with 92 patients. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. A pearson correlation analysis was used to investigate the correlation. The prognostic value of serum Clusterin and S1P was analyzed by receiver operating characteristic curve. ResultsThere were significant differences between the two groups in the degree of liver injury， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHEⅡ） score， Sequential Organ Failure Assessment （SOFA） score， the presence or absence of acute kidney injury， prothrombin time （PT）， international normalized ratio （INR）， Child-Pugh class， and C-reactive protein （all P<0.05）. The death group had significantly lower serum levels of Clusterin and S1P than the survival group （t=11.094 and 10.390， both P<0.05）. The patients with severe liver injury had significantly lower serum levels of Clusterin and S1P than those with mild or moderate liver injury （t=9.825 and 11.418， both P<0.05）. The multivariate regression analysis showed that the degree of liver injury （odds ratio ［OR］=1.260， 95% confidence interval ［CI］： 1.081 — 1.468， P<0.05）， APACHEII score （OR=1.031， 95%CI： 1.019 — 1.044， P<0.05）， SOFA score （OR=1.066， 95%CI： 1.039 — 1.094， P<0.05）， Clusterin （OR=0.899， 95%CI： 0.859 — 0.940， P<0.05）， and S1P （OR=0.824， 95%CI： 0.749 — 0.908， P<0.05） were independent risk factors for the prognosis of patients with sepsis. The ROC curve analysis showed that serum Clusterin and S1P used alone or in combination had an area under the ROC curve of 0.864， 0.861， and 0.949， respectively. Serum Clusterin and S1P were significantly negatively correlated with alanine aminotransferase， total bilirubin， PT， and INR in sepsis patients with acute liver injury （all P<0.05）. ConclusionThe sepsis patients with acute liver injury who died had significant reductions in serum Clusterin and S1P compared with those who survived， and the levels of Clusterin and S1P are closely associated with the degree of liver injury. The combination of Clusterin and S1P has a good value in predicting the prognosis of sepsis patients with acute liver injury and is expected to become a potential marker for predicting the prognosis of sepsis patients with acute liver injury.

Multilateral mechanisms are important platforms and vehicles for cooperation in traditional medicine.Relying on multilateral platforms,China is able to enhance the international influence of the domestic traditional Chinese medicine and form synergies with other member countries to enhance regional or cross-regional radiation effects in order to promote sustainable development of traditional medicine around the world.This paper focuses on China's participation in major multilateral health cooperation mechanisms,including global initiatives(WHO-led global cooperation framework,the Belt and Road Initiative),regional multilateral mechanisms(ASEAN countries,China-Japan-Korea Health Cooperation Mechanism,Shanghai Cooperation Organization(SCO),The Greater Mekong Subregion(GMS)),and cross-regional multilateral mechanisms(BRICS,Forum On China-Africa Cooperation(FOCAC),G20),and sorts out the cooperation policies and actions in traditional medicine under different mechanisms,to analyze the characteristics and challenges of the existing mechanisms in traditional medicine cooperation,and to provide evidence for China's promotion on multilateral cooperation in traditional medicine.

Objective:To compare proximal humerus internal locking system (PHILOS) and Multiloc intramedullary nail in the treatment of proximal humerus fracture-anterior dislocation.Methods:A retrospective study was performed to analyze the data of 33 patients with proximal humerus fracture-anterior dislocation who had been treated by open reduction and internal fixation from June 2015 to April 2021 at Department of Upper Limbs, Zhengzhou Orthopaedic Hospital. According to methods of internal fixation, the patients were divided into an extramedullary group and an intramedullary group. In the extramedullary group of 18 cases subjected to internal fixation with PHILOS, there were 8 males and 10 females with an age of (53.3 ± 10.6) years, and 1 2-part fracture, 15 3-part fractures and 2 4-part fractures by the Neer classification. In the intramedullary group of 15 cases subjected to internal fixation with Multiloc intramedullary nail, there were 8 males and 7 females with an age of (51.5 ± 11.2) years, and 14 3-part fractures and 1 4-part fracture by the Neer classification. The 2 groups were compared in terms of incision length, operation time, intraoperative blood loss, postoperative complications, and visual analog scale (VAS), range of shoulder motion, and Constant-Murley score at postoperative 12 months.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data ( P>0.05). All patients were followed up for (20.8 ± 4.7) months. The incision length in the intramedullary group [(11.6 ± 1.7) cm] was significantly shorter than that in the extramedullary group [(17.6 ± 2.0) cm], and the intraoperative blood loss in the former [(106.7 ± 34.4) mL] was significantly lower than that in the latter [(151.7 ± 45.7) mL] ( P<0.05). The VAS scores at 1 week and 1 month after surgery [2.0 (2.0, 3.0) and 0.0 (0.0, 1.0) respectively] in the intramedullary group were significantly lower than those in the extramedullary group [3.0 (3.0, 3.3) and 1.0 (0.0, 1.3) respectively] ( P<0.05). The external rotation of the shoulder at the last follow-up in the intramedullary group (65.3° ± 15.5°) was significantly larger than that in the extramedullary group (50.6° ± 13.9°) ( P<0.05). There were no significant differences in operation time, incidence of postoperative complications, VAS score at 12 months after operation, Constant-Murley score or range of shoulder motion at the last follow-up between the 2 groups ( P>0.05). Conclusions:In the treatment of proximal humerus fracture-anterior dislocation, open reduction and internal fixation with both PHILOS and Multiloc intramedullary nail can result in a favorable prognosis when the fracture-dislocation is well reduced and fixated. However, the Multiloc intramedullary nail may lead to better early pain relief, less surgical invasion, and better functional recovery of the external rotation of the shoulder.