Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.

Research on constructing harmonious doctor-patient relationships from the legal perspective： based on the analysis of jurisprudence on medical damage cases in obstetrics / 中国医学伦理学

This paper analyzed the legal issues existing on the medical side in 20 medical damage cases in obstetrics from January 2020 to June 2022 in China Judgment Documents Network， and hoped to explore the paths that the medical side can use for reference in building a harmonious doctor-patient relationship in the legal context. Firstly， medical institutions should establish rescue evaluation systems and early warning mechanisms for critical pregnancy and maternal， so as to ensure the health and safety of life of pregnant women and newborns， as well as prevent the occurrence of adverse obstetric events. Secondly， strengthening the cultivation of the humanistic quality among obstetric medical practitioners is the basis of the harmonious obstetrical doctor-patient relationship. Thirdly， the training and learning of relevant laws and regulations such as the Civil Code of the People’s Republic of China and the Physician Law of the People’s Republic of China should be strengthened. Fourthly， the patients’ informed consent should be respected， the process and procedures of fulfilling informed consent should be standardized by the systems， and the forms for fulfilling informed consent should be further explored. Fifthly， the medical risk-sharing mechanism should be explored and this paper suggested that postpartum women purchase obstetric accident insurance to reasonably share medical risks. Sixthly， medical social workers should be introduced， doctor-patient communication should be strengthened， and the obstetric risk awareness of the whole society should be enhanced.

SOX4 as a potential therapeutic target for pathological cardiac hypertrophy.

Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.

Functional Study of SAMD9L in Familial Gastric Cancer.

BACKGROUND: Familial aggregation occurs in approximately 10% of cases of gastric cancer. The genetic predisposition or cause of the disease in only about 40% of hereditary gastric cancer cases is known, while the genetic factors of the remaining cases remain to be studied. METHODS: Samples were collected from a family with gastric cancer, including 3 gastric cancer and 17 healthy samples. Whole-exome sequencing was performed on samples from 3 patients with gastric cancer and 1 sample from healthy peripheral blood. SAMD9L was knocked down using small interfering RNAs and short hairpin RNA. The expression of SAMD9L was detected by quantitative real-time polymerase chain reaction and Western blot in SGC-7901 cells. CCK-8 assay was used to detect the proliferation of gastric cancer cells. The migration and invasion of gastric cancer cells were detected by Transwell assay and scratch assay. The cell apoptosis was detected by flow cytometry. RESULTS: Twelve single-nucleotide variants and 9 insertions/deletions mutation sites were identified as candidate genes. Among them, SAMD9L regulates cell proliferation as a tumor suppressor gene. The experiments of knocking down SAMD9L in SGC-7901 cells revealed that reduced expression of SAMD9L significantly enhanced the proliferation, migration, and invasion of SGC-7901 cells. CONCLUSIONS: These results suggest that SAMD9L inhibits the proliferation of gastric cancer cells, thereby increasing the risk of gastric cancer in people with SAMD9L downregulation. Therefore, SAMD9L may represent a susceptibility gene of this gastric cancer family.

Inhibitory and clearance effect of azithromycin combined with levofloxacin on biofilm of different ST types of Klebsiella pneumoniae / 中国临床药理学与治疗学

AIM: Given the biofilm formation abili- ty of different ST-type Klebsiella pneumoniae, our study was aimed at exploring the inhibitory and clearance of azithromycin combined with levofloxacin on the biofilm of Klebsiella pneumoniae of different ST-types and providing a new strategy for the prevention of biofilm formation in the treatment of post-infectious Klebsiella pneumoniae. METHODS: 9 strains of Klebsiella pneumoniae from all susceptibility groups, 19 strains of Klebsiella pneumoniae producing extended-spectrum β - lactamases (ESBLs), and 37 strains of Carbapenem-resistant Klebsiella pneumoniae (CRKP) were randomly collected from the samples of patients hospitalized in the First Affiliated Hospital of Wannan Medical College from August 2019 to November 2021. The isolates were identified using VITEK MS IVD KB V3.2 and VITEK 2-Compact 60. Multilocus sequence typing (MLST) was performed to analyze the homology of each strain; crystal violet staining was used for semi -quantitative detection of biofilm to compare the differences in biofilm formation ability between different ST-type Klebsiella pneumoniae. Different ST-type strains were selected, and the partial inhibitory concentration index (FICI) was calculated by micro broth dilution method to judge the combination effect and select the optimal combination concentration; crystalline violet staining method was used to investigate the inhibition and clearance effect of azithromycin combined with levofloxacin on the biofilm of different ST-type Klebsiella pneumoniae; laser scanning confocal fluorescence microscopy was used to observe the structural changes of the biofilm of Klebsiella pneumoniae before and after the effect of the antibacterial drugs. RESULTS: MLST typing results showed that the sensitive group of Klebsiella pneumoniae strains had 8 sequences such as ST86, ST727, etc., the ESBLs group strains belonged to 14 sequence types such as ST15, ST37, ST11, etc., of which ST15 accounted for 26.32% (5 / 19). The CRKP group strains belonged to 9 sequence types such as ST11, ST15, ST656, etc., of which ST11 accounted for 48.65% (18/37), ST15 accounted for 27.03% (10/37); ST15 (ESBLs), ST11 (CRKP), ST15 (CRKP) type Klebsiella pneumoniae biofilms all reached maturity on the 5th day, the ST15 (ESBLs) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group. The ST11 (CRKP) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group (Pazithromycin>levofloxacin, and the highest clearance rate was 44.79%. CONCLUSION: There are differences in biofilm formation ability between different ST-type Klebsiella pneumoniae, and azithromycin combined with levofloxacin has a better inhibitory effect on different ST-type Klebsiella pneumoniae biofilm, conbined application can be used in the treatment of biofilm infections early stage.

Microencapsulated soil conditioner with a water-soluble core: improving soil nutrition of crop root.

Traditional level of fertilisers was used by most farmers in China with the risks about resources wasting, environmental pollution together with soil structure deterioration. It is practicable to tackle the challenges about over-fertilisation and low efficiency with microencapsulated soil conditioner (MSC), which clads the water soluble core with natural polymer. Fulvic acid (FA) can be used as core material, because it possesses the characteristics of water-soluble, fertiliser maintenance and expedient monitoring. The morphology, structure, and properties of MSC were studied and compared. The particle size of MSC was ranged from 1.58 to 2.14 mm with a similar shape which was obtained by conventional measuring method due to their soft features. This was mainly attributed to the concentration of liquid paraffin and the interaction between shell materials and calcium chloride. FTIR spectra showed that a peak appeared at 1372 cm-1, and this was ascribed to the microcapsules crosslinked and solidified by calcium ions. Sustained release experiment revealed that the microcapsules owned better fertiliser-retaining and water-retaining performances, and FA may be released as long as 750 h. Biodegradation experiments revealed that an obvious pore structure was found on the surface of microspheres after 30 d of degradation, and this was consistent with the sustained release experiment. Pot experiment illustrated that the plants cured with the microcapsules showed significant growth trend and grew up to 9.2 cm with a maximum rate, and this revealed that MSC owned better performance of promoting the growth of crop root.

Preparation and application properties of sustainable gelatin/chitosan soil conditioner microspheres.

Traditional soil conditioners can be used as drugs to regulate elements in soil due to overuse or pollution. There are some negative effects such as low efficiency, hard to degrade and harmful to the environment when they are used. Soil conditioners prepared from sustainable macromolecules can reduce or eliminate these negative effects. In this work, gelatin (GL), chitosan (CS), magnesium ammonium phosphate (MAP) and fulvic acid (FA) were combined and prepared into GL/CS/MAP-FA soil conditioner microspheres with core-shell structure through emulsion crosslinking method. Scanning electron microscopy (SEM) and Fourier infrared spectroscopy (FT-IR) analysis results clarified the surface composition of the microspheres and revealed the good coating performance of GL/CS shell materials. The thermal stability of the microspheres was measured by thermogravimetric analysis (TGA). Water-retention, degradation and crop cultivation showed that these microspheres owned good biocompatibility, which can extend the water-retention time of the soil, settle free heavy metal ions and promote crop growth. The load of fertilizer in the microsphere can effectively prolong the release cycle and improve the utilization rate of fertilizer.

Survey and Reflection on the Ethical Cognition of Human Sperm Bank among Sperm Donors / 中国医学伦理学

Objective:To investigate the ethical cognition of human sperm among the volunteers who intend to donor sperm,and to analyze the voluntteers' thoughts for donor behavior and its countermeasures.Methods:A questionnaire survey was conducted to investigate the volunteers who were the first time consulted sperm donation in the human sperm bank of the affiliated reproductive hospital of Shandong university.The cognition on the purpose of sperm,the causes of sperm shortage,privacy protection of the offspring,and the future of sperm banks in China were collected.Results:Donors were not well known the uses of sperm and privacy protection of the offspring.They thought traditional values and ethical worry caused sperm shortage and worried about the future of human sperm banks in China.Conclusion:The overall cognition on the sperm bank of the volunteers still exist certain one-sidedness and blind,which has seriously affected the enthusiasm of volunteers to donate sperm.The relevant departments should pay more attention to this,focus on promoting the propaganda and supervision work of ethical system of human sperm bank,construct objective,justice,and dedicative atmosphere for sperm donation,in order to dispel the volunteers' psychological concerns,and promote the healthy,fast and sustainable development of human sperm bank.

Establishment and identification of hu-PBL-SCID mice model of human renal cell carcinoma / 重庆医科大学学报

Objective:To investigate the feasibility of establishing a human renal cell carcinoma model in human peripheral blood lymphocyte-engrafted to severe combined immunodeficient(hu-PBL-SCID)mice.Methods:The biological and immunological features of mice were evaluated after intra-peritoneal injection of human peripheral blood lymphocytes(PBL)and subcutaneous implantation of human renal cell carcinoma cells(RCCCs).Results:(1)Subcutaneous tumors developed in all the mice given human PBL and RCCCs.The latency period was significantly prolonged,and the tumor size was markedly depressed,as compared with the mice given RCCCs(P