Targeted protein degradation(TPD)technology is an emerging approach that utilizes intracellu-lar proteasome or lysosome systems to eliminate disease-causing proteins,providing novel strategies for dis-ease treatment.Compared with conventional therapies,TPD has advantages such as targeting"undruppable"proteins,overcoming drug resistance and high selectivity.Among them,proteolysis-targeting chimeras(PRO-TACs)and molecular gels are representative methods,which have achieved significant progress in E3 ligase expansion,linker design,and delivery systems,and are gradually entering clinical research.PROTACs and mo-lecular glues can not only target key oncoproteins and overcome resistance,but also modulate immune respon-ses for therapeutic purposes,demonstrating broad clinical application prospects.This article reviews the re-search progress of the two types of technologies and their current application status in cancer treatment,and discusses their potential and challenges in efficacy monitoring and individualized medication from the perspec-tive of laboratory medicine.

OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Hepatic encephalopathy （HE） is a common severe liver disease syndrome in clinical practice and is one of the critical and severe diseases in internal medicine， and more than half of liver failure patients diagnosed with overt HE have a survival time of less than 1 year. A comprehensive analysis of the complex pathogenesis of HE and the development of diagnosis and treatment regimens based on evidence-based medicine are of great importance for alleviating high medical resource consumption， high medical expenses， and high incidence and mortality rates in clinical practice. The latest studies have shown that the intestinal tract and the central nervous system can perform bidirectional continuous interaction and signal transmission and regulate the function of inflammation signals， molecules， cells， and organs， which is known as neuroimmune communication and is highly consistent with the main pathological features of HE. With a focus on the mechanism of neuroimmune communication in HE， this article reviews the association between inflammation signal transduction via the gut-brain axis and neurotransmitter regulation and its role in neuroimmune communication in HE， which provides new ideas for the clinical diagnosis and treatment of HE and the research and development of related drugs.

ObjectiveExploring the role of microRNA126 （miRNA126） in chronic kidney disease combined with atherosclerosis （CKD AS） by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group， model group， losartan group， and low， medium， and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low， medium， and high dose groups （6.0， 12.0， 24.0 g·kg^-1·d^-1） of Shenshuai Xiezhuo decoction and the losartan group （20 mg·kg^-1·d^-1） were gavaged， and the corresponding intervention was carried out for eight weeks. Then， the rats were killed， and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats： blood creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） and Masson staining of aortic tissue and pathological observation under a light microscope were carried out， and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA levels of miRNA126， PI3K， Akt， and mTOR in rats， and Western blot was used to determine the protein expression levels of phosphorylated （p）-PI3K， PI3K， p-Akt， Akt， p -mTOR， mTOR， benzyl chloride 1 （Beclin-1）， and microtubule-associated protein light chain 3Ⅱ/Ⅰ （LC3Ⅱ/LC3Ⅰ）. ResultCompared with the sham operation group， the serum SCr， BUN， TC， TG， and LDL-C in the model group were significantly increased （P<0.01）. Compared with the model group， the SCr， BUN， TC， TG， and LDL-C were decreased in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction （P<0.05）. Compared with the sham operation group， thickening plaques， infiltration of mononuclear macrophages， a small number of foam cells， disordered arrangement of smooth muscle fibers in the tunica media， and increased collagen fibers were observed in the model group， and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group， the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group， the expression of miRNA126 in the aortic tissue of the model group was significantly decreased （P<0.01）， and the mRNA expressions of PI3K， Akt， and mTOR were significantly increased （P<0.01）. Compared with the model group， the expression of miRNA126 in the aortic tissue of rats in high， medium， and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased （P<0.01）， while the mRNA expressions of PI3K， Akt， and mTOR were significantly decreased （P<0.01）. Compared with the sham operation group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the model group were significantly increased （P<0.01）， while the protein levels of Beclin-1， LC3Ⅰ， and LC3Ⅱ were significantly decreased （P<0.01）. Compared with the model group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction were decreased （P<0.05）， while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased （P<0.05）. ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats， and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126， restores the autophagy of aortic endothelial cells， protects the damage of CKD vessels， reduces the formation of As plaques， and slows the development of cardiovascular complications.

ObjectiveTo introduce a fixation technique with the modified levonorgestrel-releasing intrauterine system （LNG-IUS） and evaluate its efficacy in the treatment of adenomyosis patients with previous LNG-IUS expulsion. MethodsA retrospective analysis was done on 22 adenomyosis patients who underwent modified LNG-IUS fixation due to LNG-IUS expulsion at three hospitals from June 2022 to June 2023. The baseline clinical characteristics， operative and postoperative details were collected and analyzed. The Visual analogu scale （VAS） scores and pictorial blood loss assessment chart （PBAC） scores were measured and compared before， 3 and 6 months after the LNG-IUS fixation. ResultsThe mean operative time was （19.51±7.41） min and intraoperative bleeding was （6.71±5.30） mL. Of the patients， 13 were operated under local anaesthesia and the other 9 under intravenous anaesthesia. There were 4 operations performed by a resident doctor， 15 by an attending doctor and 3 by a senior doctor. No intraoperative or postoperative complication was found. The mean follow-up was 11.51 months and no patient had a recurrence of LNG-IUS expulsion during the follow-up period. The mean level of hemoglobin at 1 month after operation was significantly higher than that before （P<0.001）. VAS scores and PBAC scores at 3 and 6 months postoperatively were all improved significantly than those preoperatively （P<0.001）. ConclusionsEffectively preventing the recurrence of LNG-IUS expulsion， modified LNG-IUS fixation is a safe and efficient method for adenomyosis patients with previous LNG-IUS expulsion. Modified LNG-IUS fixation deserves the clinical application due to its easy operation and wide range of use on women.

Objective To understand the composition of death causes of residents in Tianzhu Tibetan Autonomous County,Wuwei City,and to analyze the current situation of life expectancy and life loss of residents,so as to provide evidence for disease control and health promotion.Methods According to the international classification of diseases(ICD-10),the population data and death cause monitoring data of Tianzhu Tibetan Autonomous County in 2021 were analyzed,standardized with the data of the seventh national census,and analyzed with SPSS 21.0 software and life expectancy statistics.Results The crude mortality rate of residents in Tianzhu Tibetan Autonomous County was 642.25/100 000,The male crude mortality(727.12/100 000)rate was higher than the female(553.29/100 000).The overall life expectancy was 79.07 years.The life expectancy in males was 76.77 years and the life expectancy in females was 81.47 years.The first five causes of death were circulatory system(mortality 270.14 per 100,000),nervous system(mortality 159.57 per 100,000),malignant tumor(mortality 101.97 per 100,000),respiratory system(mortality 27.81 per 100,000)and gastrointestinal disease disease(mortality 26.48 per 100,000).The first five places of AYLL were injury and poisoning(24.81 years/person),spirit and blood(15.42 Years/person),infectious diseases(13.06 years/person),malignant tumor(11.78 Years/person)and urogenital diseases(9.94 years/person).Conclusion The highest mortality rate in the 2021 Bairi Tibetan Autonomous County was circulatory system disease,and the major causes of premature death were injury and poisoning.

The current linear economy model relies on fossil energy and increases CO₂ emissions, which contributes to global warming and environmental pollution. Therefore, there is an urgent need to develop and deploy technologies for carbon capture and utilization to establish a circular economy. The use of acetogens for C1-gas (CO and CO₂) conversion is a promising technology due to high metabolic flexibility, product selectivity, and diversity of the products including chemicals and fuels. This review focuses on the physiological and metabolic mechanisms, genetic and metabolic engineering modifications, fermentation process optimization, and carbon atom economy in the process of C1-gas conversion by acetogens, with the aim to facilitate the industrial scale-up and carbon negative production through acetogen gas fermentation.
Fermentation ; Gases/metabolism* ; Carbon Dioxide/metabolism* ; Metabolic Engineering ; Carbon/metabolism*

Objective:To explore the prognostic value of platelet-lymphocyte ratio (PLR) for esophageal cancer patients based on propensity score matching.Methods:A retrospective analysis was conducted on the clinical data of 272 esophageal cancer patients in Shanxi Province Cancer Hospital from January 2012 to December 2018. The optimal cut-off value of PLR, which was determined using the Youden index, was used to classify patients into high- and low-PLR groups. Propensity score matching (PSM) was employed to reduce the selection bias of patients. The prognostic factors were analyzed through univariate and multivariate Cox regression. The Kaplan-Meier method and the Log-Rank test were adopted for survival analysis.Results:Cox univariate analysis shows that prognosis of esophageal cancer patients was related to gender, smoking history, TNM stage, body mass index (BMI), carcinoembryonic antigen (CEA), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR) and PLR ( χ2=6.63, 7.08, 30.38, 10.40, 12.95, 13.21, 4.52, 4.06, 7.77, P < 0.05). The optimal cut-off value of PLR was 159.93. Before PSM, there existed statistically significant differences in SII and LMR between the high-PLR ( n = 103) and low-PLR groups ( n = 169) ( χ2=52.23, 3.51, P<0.05). After PSM, there existed no statistical difference in prognostic indicators between the high-PLR ( n=62) and low-PLR groups ( n=62), suggesting that both groups were comparable. As revealed by Cox multivariate analysis, TNM stage, BMI, CEA, and PLR were independent risk factors for the prognosis of esophageal cancer patients both before and after PSM. The survival time of patients in the high-PLR group was significantly shorter than that in the low-PLR group ( χ2=3.29, P < 0.05). Conclusions:PLR hold critical value in evaluating the prognosis of esophageal cancer patients. A higher PLR is associated with a shorter survival time. Individualized intervention for PLR may play a positive role in improving the prognosis of patients.

Long-chain dicarboxylic acid (DCA), a building block for synthesizing a variety of high value-added chemicals, has been widely used in agriculture, chemical, and pharmaceutical industries. The global demand for DCA is increasing in recent years. Compared with chemical synthesis which requires harsh conditions and complicated processes, fermentative production of DCA has many unparalleled advantages, such as low cost and mild reaction conditions. In this review, we summarized the chemical and microbial synthesis methods for DCA and the commercialization status of the fermentation process. Moreover, the advances of using molecular and metabolic engineering to create high-yielding strains for efficient production of DCA were highlighted. Furthermore, the challenges remaining in the microbial fermentation process were also discussed. Finally, the perspectives for developing high titer DCA producing strains by synthetic biology were proposed.
Fermentation ; Dicarboxylic Acids/metabolism* ; Metabolic Engineering ; Technology

Abstract In recent years, the overall incidence of scoliosis in children and adolescents in China is on the rise, and it has become the third largest "killer" affecting the health of children and adolescents in China after obesity and myopia. The dysfunction caused by spinal deformity has no obvious pathological manifestations or clinical symptoms in children and adolescents (except for severe scoliosis). It is easy to be ignored in the early stage, but if it is not intervened in time, this will cause serious damage to the long term prognosis and quality of life of the patients. Therefore, through early scoliosis screening, we can effectively monitor the spinal health status of children and adolescents in China, ensure timely diagnosis of the disease, timely intervention (brace and other conservative treatment), and play the role of early prevention. Avoid further deterioration of scoliosis and surgical intervention. This article will focus on the research progress of screening and conservative treatment of scoliosis.