Objective To investigate the effects of peroxisome proliferator activated receptor-gamma(PPARγ)gene silen-cing in human bone marrow stromal cells(HS-5)on hematopoietic function in bone marrow-suppressed mice,and to explore the potential mechanisms involved.Methods A bone marrow-suppressed mouse model was established by whole-body X-ray irradi-ation.Two hours after modeling,the mice were randomly divided into three groups:experimental group(intravenous injection of PPARγ RNAi-interfered HS-5 cells through the tail vein),control group(intravenous injection of PPARγ RNAi-uninterfered HS-5 cells through the tail vein),and blank group(intravenous injection of an equal amount of saline through the tail vein),with 5 mice in each group.Peripheral blood routine tests were performed before,24 hours after,1 week after,and 2 weeks after radio-therapy.In vitro osteogenic and adipogenic induction was performed in cells,and the cells were divided into experimental group(PPARγ RNAi-interfered HS-5 cells),control group(PPARγ-uninterfered HS-5 cells),and blank group(HS-5 cells without os-teogenic/adipogenic induction).Osteogenic/adipogenic staining was observed.The effects of PPARγ gene-silenced HS-5 cells on mouse bone marrow hematopoietic stem cells(HSCs)were detected by CCK-8 proliferation assay.The groups included experi-mental group(PPARγ RNAi-interfered HS-5 cells were co-cultured with mouse HSCs after 3 days of osteogenic induction dif-ferentiation),positive control group(HS-5 cells treated with 50 μmol/L PPARγ inhibitor were co-cultured with mouse HSCs af-ter 3 days of osteogenic induction differentiation),negative control group(PPARγ RNAi-uninterfered HS-5 cells were co-cul-tured with mouse HSCs after 3 days of osteogenic induction differentiation),and blank group(Mouse HSCs were cultured alone without co-culturing with HS-5 cells).Results After radiotherapy,the hematological parameters of mice in each group showed a decreasing trend initially,and then increased.One week after radiotherapy,there were significant differences in platelet and white blood cell levels among the three groups(experimental group＞control group＞blank group,all P＜0.05).Two weeks after radiotherapy,there were significant differences in the percentage of adipocyte vacuole area among the three groups(experi-mental group＜control group＜blank group,all P＜0.05).Pearson correlation analysis showed a negative correlation between hematological parameters and PPARγ expression levels(all P＜0.05),as well as a negative correlation between hematological parameters and the percentage of adipocyte vacuole area(all P＜0.05).After in vitro osteogenic/adipogenic induction differenti-ation,compared to the control group,the experimental group showed a significantly lower proportion of orange-red cells and a significantly higher proportion of red calcium nodules.After 3 days of osteogenic induction differentiation,the experimental group,positive control group,and negative control group of human bone marrow stromal cells were co-cultured with mouse HSCs,while HSCs were solely cultured in the blank group.The results showed that after 24 h,48 h and 72 h of co-culture,the A values of mouse HSC cells in the experimental group and positive control group were higher than those in the negative control group and blank group(all P＜0.05).Conclusion Silencing of the PPARγ gene in HS-5 cells implanted into bone marrow-sup-pressed mice contributes to enhanced hematopoietic function in mice.After interference and silencing of the PPARγ gene,the os-teogenic differentiation ability of HS-5 cells is enhanced,while the adipogenic differentiation ability is weakened.Furthermore,osteogenic-induced HS-5 cells can further enhance the proliferation capacity of mouse HSCs.

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.

Objective To improve the quality of prescriptions and promote the rational drug application of Dingqing Tablets by investigating the outpatient prescriptions in a tertiary A hospital. Methods A total of 4 796 prescriptions of outpatient pharmacy patients from August 1, 2020 to August 1, 2021 were extracted from the hospital information system by the hospital information software, focusing on the analysis of indications, usage and dosage, drug interaction, etc. Results 10 departments including hematology department and geriatrics department were used Dingqing Tablets, and the irrationality was mainly manifested in the superposition of drug flavors and drug interactions. Conclusion Dingqing tablets were widely used in clinic and had remarkable curative effect. However, there are certain risks in the use of Dingqing tablets. It is necessary to add medication education and supervision to promote the safe and rational use of drugs in clinic.

Objective To investigate the relieving effect of Yinlian Tongfeng granules on adjuvant arthritis rats. Methods A complete Freund adjuvant model was built for this study. 48 rats were randomly divided into control group, model group, Yinlian Tongfeng granules high, medium and low dose group (15.4g/kg, 7.7g/kg, 3.8g/kg). After the drug intervention, arthritis index, ankle swelling rate, formaldehyde induced pain score were recorded. Elisa method was used to detect IL-4, IL-10 and the content of PK1, PK2. The pathological changes of toe pad in rats were observed. Results Compared with the model control group, Yinlian Tongfeng granules groups significantly inhibited the ankle swelling, reduced the pain reaction caused by formaldehyde (P<0.01), significantly increased the content of anti-inflammatory factors IL-4 and IL-10 (P<0.01), and decreased the content of PK1 and PK2 (P<0.01). Toe edema and lymphocyte infiltration were alleviated. Conclusion Yinlian Tongfeng granules have a significant inhibitory effect on adjuvant arthritis, suggesting that it has a potential therapeutic application for rheumatoid arthritis.

Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Ossifying fibroma (OF) and fibrous dysplasia (FD) are two fibro-osseous lesions with overlapping clinicopathological features, making diagnosis challenging. In this study, we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations (CNAs) using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples. Freshly frozen tissue specimens from OF (n = 29) and FD (n = 28) patients were obtained for analysis. Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection (LCM), with ~30-50 cells (5 000-10 000 µm
DNA Copy Number Variations ; Diagnosis, Differential ; Fibroma, Ossifying/genetics* ; Fibrous Dysplasia of Bone/genetics* ; Galactosyltransferases ; Humans ; Jaw ; Neoplasm Recurrence, Local ; Nuclear Proteins

Prokineticin 2 (PK2) is a newly discovered chemokine, which participates in various physiological functions of the body by binding to receptors PKR1 and PKR2. PK signaling pathway is a newly discovered important regulatory pathway for the occurrence and maintenance of pain after tissue injury and nerve injury in recent years. It plays a key role in regulating injury-related nociceptive events and is a potential therapeutic target for many diseases. The activation of PKRs can induce pain sensation and participate in the sensitivity of pain receptors to different stimuli. The PK system (PKs and PKRs) is an important link involved in inflammation and pain transmission in immune cells. PK2 is involved in the regulation of pain perception by activating PKR1 and PKR2 on primary sensory neurons. In rat primary sensory neurons, PK2 also enhances gated ion channel current through the PKC signaling pathway, inhibits GABA-activated currents, and sensitizes purine nucleotide P2 receptor (P2X). This paper reviews the research progress of PK2 in physical pain. We hope to find new drugs for the treatment of inflammatory pain that target the PKs signaling pathway in future studies.

Objective To investigate the anti-inflammatory and analgesic effects of the active fractions of Tongfeng granules on rats with arthritis induced by complete Freund's adjuvant. Methods 56 SD rats were randomly divided into seven groups, blank group, model group, total flavonoids group, total organic acid group, total alkaloid group, Tongfeng granule group and positive control group. Except for the blank group, the remaining 6 groups established joints pathological model of inflammation. 15 days after the successful modeling, intragastric drug administration was continued for 30 days. The swelling of ankle joint, WBC, N%, IL-6, IL-10, TNF-α and the histopathology of joint were measured. Results Comparing with the model group, each effective fraction group of Tongfeng granules, Gout granules and positive control group decreased the ankle joint swelling rate significantly (P<0.01) and reduced fibrous tissue proliferation. There was no significant difference in WBC and N% of neutrophils. They significantly reduce the level of serum IL-6 and TNF-α, and increase the level of IL-10 (P<0.05, P<0.01). Conclusion This study clarifies the anti-inflammatory and analgesic effects of active fractions of Tongfeng granules and provides a basis for further clinical medication and preparation development.