Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.

Objective To evaluate the postoperative survival quality in the patients with heart valve re-placement (HVR) in Three Gorges Reservoir area,and to analyze its main influencing factors.Methods A to-tal of 343 valvular heart disease patients from Three Gorges Reservoir area who received HVR treatment for the first time in this hospital from January 2019 to December 2021 were selected by the convenience sampling method.The general data questionnaire and the MOS 36-item short form health survey (SF-36) were adopted to conduct the survey.The main influencing factors affecting the survival quality were analyzed.Results Af-ter HVR,the physical components summary (PCS) score of SF-36 was 238.0±73.6,and the mental compo-nents summary (MCS) score was 254.8±83.6,and the scores in each dimension were significantly lower than those of the Chinese norm (P<0.05).The multiple stepwise linear regression analysis results showed that the age,gender,place of residence,education level,postoperative time,complications and readmission were the influencing factors of PCS and MCS scores (P<0.05).Conclusion The survival quality of the patients af-ter HVR is different from that of healthy population.The targeted intervention could be carried out according to the influencing factors of the survival quality of the patients,so as to improve their survival quality.

This report describes a case of maturity-onset diabetes of the young(MODY)type 3(MODY3)complicated with type 5(MODY5),including the patient's clinical features,diagnosis,and treatment,and reviews relevant literature.Using next-generation sequencing of MODY(types 1-14)gene exons and Sanger sequencing for verification,the patient and her mother were assessed.Based on the clinical phenotype and genetic test results,the patient was diagnosed as MODY3 combined with MODY5.Treatment included insulin and linagliptin,with monitoring of blood glucose changes.Clinicians should enhance their understanding of MODY clinical phenotypes.In adolescents with diabetes who have congenital pancreatic and renal developmental defects,elevated high-density lipoprotein cholesterol,no spontaneous ketosis,insulin secretion defects,negative pancreatic autoantibodies,no significant insulin resistance,and who are not obese,gene testing should be conducted to screen for MODY.Accurate diagnosis and personalized treatment can aid in achieving glycemic control,improving quality of life,and optimizing reproductive planning.

Objective: To explore the clinical dosimetry advantages of automated plan of IMRT for postoperative esophageal cancer and the dose prediction accuracy of the constructed 3D U-Res-Net model． Methods: A total of 110 postoperative esophageal cancer (middle and upper) cases treated by IMRT were considered in the study，of which 90 cases were randomly selected for training of deep learning prediction model．The deep learning prediction model and Auto-Plan module ( Philips pinnacle3 16. 2 ) were used to predict the three-dimension dose distribution and redesigned the remaining 20 cases respectively ，and the results obtained were compared with manual plan. Results : The average DSC value between the deep learning prediction plan and the manual plan was greater than 0. 92 in isodose surface，and the average Hausdorff distance HD95 of the isodose surface was 0. 58－0. 62 cm ; The V20 ，V30 ，Dmean of total lung were slightly lower than those of manual plan (P ＜0. 05 ) for the prediction model， meanwhile，the D2 ，D50 ，Dmean，HI of the target area and V30 of total lungs were better than those of manual plan(P ＜0. 05) for Auto-Plan ; Three-dimensional dose distribution of the three groups and the corresponding DVH curve showed that the three-dimensional dose distribution of the three groups had a little differences，and the DVH curves of the target area and organs at risk had a good agreement． Conclusion Auto-Plan can realize the design of automated plan for postoperative esophageal cancer，while the deep learning prediction model can realize the accurate prediction of the 3D dose distribution.

Zearalenone is one of the most widely polluted Fusarium toxins in the world, seriously endangering livestock and human health. Zearalenone hydrolase (ZHD) derived from Clonostachys rosea can effectively degrade zearalenone. However, the high temperature environment in feed processing hampers the application of this enzyme. Structure-based rational design may provide guidance for engineering the thermal stability of enzymes. In this paper, we used the multiple structure alignment (MSTA) to screen the structural flexibility regions of ZHD. Subsequently, a candidate mutation library was constructed by sequence conservation scoring and conformational free energy calculation, from which 9 single point mutations based on residues 136 and 220 were obtained. The experiments showed that the thermal melting temperature (T_m) of the 9 mutants increased by 0.4-5.6 ℃. The S220R and S220W mutants showed the best thermal stability, the T_m of which increased by 5.6 ℃ and 4.0 ℃ compared to that of the wild type. Moreover, the thermal half-inactivation time at 45 ℃ were 15.4 times and 3.1 times longer, and the relative activities were 70.6% and 57.3% of the wild type. Molecular dynamics simulation analysis showed that the interaction force at and around the mutation site was enhanced, contributing to the improved thermal stability of ZHD. The probability of 220-K130 hydrogen bond of the mutants S220R and S220W increased by 37.1% and 19.3%, and the probability of K130-D223 salt bridge increased by 30.1% and 12.5%, respectively. This work demonstrated the feasibility of thermal stability engineering strategy where the structural and sequence alignment as well as free energy calculation of natural enzymes were integrated, and obtained ZHD variants with enhanced thermal stability, which may facilitate the industrial application of ZHD.
Humans ; Hydrolases ; Zearalenone ; Trichothecenes ; Gene Library ; Hydrogen Bonding

Objective:To evaluate the performance of the automated digital cell morphology instrument in detecting platelet (PLT) clumps.Methods:A total of 4271 blood samples whose PLT reached the reviewing rules of thrombocytopenia were selected from inpatients having blood analysis in Xijing Hospital from January 1 st to June 30 th, 2019, including 2 200 males and 2 071 females,with a median age of (35±7.03) years old. The smears for these cases were made, stained by Wright-Giemsa, and examined to capture PLT clumps by digital cell morphology system and manual microscope separately. The digital cell analysis system (hereinafter referred to as the instrument method) as an evaluation method and the microscope method as a reference method were used to calculate the positive rate of platelet clump detection and evaluate the comparison of two methods and bias assessments. The chi-square test was used to compare counting data rates. Results:Among 4, 271 samples reaching the reviewing rule of thrombocytopenia, 128 cases with platelet clumps were detected by manual microscope(initial) with a positive detection rate of 96.24%, and a total 133 of cases with PLT clumps were detected by microscope (initial+reconfirmation) with a positive detection rate of 100 %. Meanwhile, 129 cases with platelet clumps were detected by instrument method with a positive detection rate of 96.9%. There was no significant difference in terms of positive rate of PLT clumps detection between the instrumental method and the microscope method (initial) ( χ2 =0.115, P=0.73); the positive rate of clumps detection by the instrumental method was lower than microscope method (initial+reconfirmation), and the difference was statistically significant (χ 2 =4.061, P=0.04). For instrument method, the positive rate of PLT clumps detection by simultaneous observation of RBC analysis interface+PLT aggregation interface+WBC analysis interface was higher than only observation of PLT aggregation interface, and the difference was statistically significant (χ 2 =5.090, P=0.02). The average error of the deviation of PLT counting results before and after correction of the cases with PLT plumps missed by instrument method was significantly higher than microscope method (initial), and the difference was statistically significant (χ 2 =56.26, P<0.001). Conclusion:The automated digital cell morphology system has a good consistency with manual microscope(initial) in terms of the sensitivity of platelet clumps detection and can be used as a supplementary method for detecting platelet aggregation.

Objective    To investigate the short-term quality of life in patients after single-direction video-assisted thoracic surgery (VATS) for lung cancer, and explore the related influencing factors. Methods    Patients who underwent single-direction VATS for lung cancer in the Department of Thoracic Surgery, West China Hospital, Sichuan University from July 2020 to August 2021 were continuously selected. The QLQ-C30 and QLQ-LC13 were used to evaluate the quality of life of the patients after the surgery, and the influencing factors were analyzed. Results    A total of 193 patients were collected. There were 73 males aged 59.44±11.40 years, and 120 females aged 53.73±11.15 years. The QLQ-C30 score of the patients after single-direction VATS for lung cancer was 69.09±20.21 points. Univariate analysis and Pearson correlation analysis showed that age, occupation, anesthesia time, postoperative complications, postoperative antibiotic use time, postoperative hospital stay, insomnia, economic stress, hemoptysis, chest pain, dysphagia, arm or shoulder pain were associated with the quality of life (P≤0.05). The results of multiple regression analysis showed that anesthesia time, economic pressure, insomnia and chest pain had a significant impact on the overall quality of life 30 days after the surgery (P≤0.05). Conclusion    The anesthesia time, economic pressure, insomnia and chest pain are independent influencing factors for the quality of life after the VATS lung cancer surgery.

Objective     To analyze the clinical characteristics of the Guang’an Omicron epidemic and summarize the management experiences and practices in pandemic prevention and control of major infectious diseases. Methods     Retrospective analysis was performed on patients infected with coronavirus disease (COVID-19), afterwards treated and observed in the isolation ward of Guang’an People’s Hospital and the shelter of Guang’an City from May 9 to June 26, 2022. The characteristics of patients at different age stages and the related factors affecting the severity, re-positive and negative conversion was analyzed. Results     Finally 1 278 patients were collected, including 508 males and 770 females, with an average age of 41.3±22.6 years. Among them, 1 054 patients were asymptomatic carriers. The overall severe rate was 0.86%, the severe rate of the high-risk group was 3.06%. The median negative conversion time was 10.0 days and re-positive rate was 7.36%. Patients aged>60 years were 2.589 times more likely to have a longer negative conversion time than those aged≤60 years (95%CI 1.921-3.489, P<0.001). Conclusion     The clinical characteristics of Guang’an COVID-19 epidemic are mainly that the elderly with high risk factors are more likely to develop severe cases, have longer clearance time, and re-positve is more likely to occur.

The phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a common oncogene located in the 10q23.3 region on the long arm of human chromosome l0, which regulates a variety of biological processes such as proliferation, survival, cell structure, motility, energy metabolism and genomic stability. Inactivation of PTEN is prevalent in almost all malignancies and correlates with tumor progression. Thyroid malignancies are among the most common endocrine malignancies, and PTEN has been shown to be critically associated with their development. The aim of this review is to describe the structural function of PTEN, as well as to summarize and discuss the recent findings of PTEN in thyroid malignancies.