ObjectiveThis paper aims to investigate the intervention effect and molecular mechanism of Gancao Fuzitang （GCFZT） in knee osteoarthritis （KOA）. MethodsNetwork pharmacology was employed to predict the key targets and signaling pathways of GCFZT. Fifty SD rats were randomly divided into a sham group， a model group （KOA）， a low-dose GCFZT group （GCFZT-L， 2.8 g·kg^-1）， a high-dose GCFZT group （GCFZT-H， 5.6 g·kg^-1）， and a positive drug celecoxib group （Celecoxib， 20 mg·kg^-1）， with 10 rats in each group. The rats in the sham group and the model group were given an equal volume of distilled water. Except for the sham group， the other four groups underwent anterior cruciate ligament transection to establish the KOA rat model. After successful modeling， the rats in each group received intragastric administration once a day for eight consecutive weeks. The structural changes of cartilage and subchondral bone were assessed via micro-computed tomography （micro-CT） and histological staining. The levels of inflammatory factors in the serum， such as interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured using an enzyme linked immunosorbent assay （ELISA） kit. Real-time quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry were used to detect changes in the expression of autophagy-related proteins such as microtubule-associated protein 1 light chain 3B （LC3B）， selective autophagy junction protein 62 （p62）， and autophagy key molecule yeast Atg6 homolog （Beclin-1） in articular cartilage， as well as key molecules of the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. ResultsNetwork pharmacology analysis suggests that GCFZT may exert anti-osteoarthritic effects through regulating the PI3K/Akt/mTOR pathway. In vivo experiment shows that GCFZT can significantly improve cartilage degeneration and attenuate subchondral bone destruction in KOA rats. Detection results of inflammatory factors in the serum reveal that， compared with those in the sham group， the levels of IL-6， IL-1β， and TNF-α in the serum of rats in the KOA group are significantly increased （P<0.05）. Compared with those in the KOA group， the levels of these three inflammatory factors in the GCFZT-L， GCFZT-H， and Celecoxib groups were significantly decreased （P<0.05）. However， there was no statistically significant difference in these three inflammatory factor levels between the GCFZT-H group and the celecoxib group. These findings suggest that GCFZT can effectively inhibit the systemic inflammatory response in KOA rats. Mechanism research indicates that GCFZT inhibits activation of the PI3K/Akt/mTOR pathway， thereby enhancing autophagic activity and improving chondrocyte function and matrix degeneration. ConclusionGCFZT improves cartilage and subchondral bone damage in KOA rats by inhibiting the PI3K/Akt/mTOR signaling pathway and promoting autophagy. These findings provide theoretical evidence for the application of GCFZT in the prevention and treatment of osteoarthritis.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

Objective:To construct a risk prediction model for unplanned readmission of patients undergoing cardiac resynchronization therapy (CRT) and verify the performance of the model.Methods:Using convenience sampling, patients who underwent CRT at the Department of Cardiovascular of the First Affiliated Hospital of Zhengzhou University from July 2017 to July 2020 were selected as the modeling group ( n=279) and the internal validation group ( n=120). CRT patients admitted to the Department of Cardiovascular of the First Affiliated Hospital of Zhengzhou University from August 2021 to August 2022 due to the same or related diseases were selected as the external validation group ( n=86). Multivariate Logistic regression was used to explore the influencing factors of unplanned readmission of CRT patients and establish the prediction model. The fitting effect and discrimination of the model were evaluated through the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve. The nomogram was established based on R-4.1.2 and Rstudio software. Results:The multivariate Logistic regression analysis showed that creatinine, left atrial diameter, pulmonary artery systolic pressure, New York Heart Association (NYHA) classification, and body mass index (BMI) were risk factors for unplanned readmission in CRT patients, with statistically significant differences ( P<0.05). The prediction model formula was: P=1/{1+exp[- (0.792×creatinine+1.408×left atrial inner diameter+0.887×pulmonary artery systolic pressure+0.769×NYHA classification-0.970×BMI-2.266) ]}. The area under the ROC curve was 0.874, the maximum value of the Jordan index was 0.636, the optimal threshold was 0.256, the sensitivity was 0.826, and the specificity was 0.810. The accuracy of internal validation and external validation was 90.00% and 90.70%, respectively. Conclusions:The constructed prediction model for unplanned readmission of CRT patients has good predictive performance, and the visualized nomogram improves the practical performance of the model. It helps medical and nursing staff identify high-risk groups of unplanned readmission of CRT patients in the early stage and provides a basis for formulating nursing strategies for different risk groups.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

Abstract Comprehensive sexuality education is an important part of quality education, primary and secondary schools are the most suitable places for sex education. This paper sorts out the current status of sexuality education for primary and secondary school students in developed countries after presenting the overall significance of school based sexuality education, and further points out the problems and urgency of sexuality education for primary and secondary school students in China. It also put forward the way to new directions for advocacy, including the comphrehensive sexuality education curriculum system, training of sexuality education teachers, the positive and active role of families, as well as social and community support for sexuality education in schools.

Objective: To describe the status quo of overweight and obesity among children aged 3 to 5 in Beijing and Tokyo, and to explore its relationship with lifestyle. Methods: Using the method of cluster stratified random sampling, a sample of 444 children aged 3-5 years from Beijing and Tokyo were selected in Oct. and Nov. of 2019. Height, weight and lifestyle were measured. Overweight and obesity among children in the two cities and its relationship with lifestyle were compared and analyzed. Results: Average level of BMI, rate of overweight and obesity of children in Beijing(25.28%) were higher than those in Tokyo( 18.44 %). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with physical activity before breakfast( χ 2=29.14, 31.18, P <0.05). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with different snack frequency after dinner( χ 2=24.72, 21.93, P <0.05). Logistic regression analysis further showed that children s lack of physical activity before breakfast in Beijing is positively related to overweight and obesity( OR= 1.45, 95%CI =1.10-2.68). Beijing children who often eat snacks after supper ( OR=2.56, 95%CI =1.44-3.57,) and sometimes eat snacks were positively correlated with the occurrence of overweight or obesity ( OR=1.72, 95%CI =1.21-2.72). Conclusion The prevalence of overweight and obesity among preschool children in Beijing is higher than that in Tokyo. Potential risk factors for overweight and obesity among infants in Beijing include lack of physical activity before breakfast and frequent snacking after dinner.

The basic pathological change of diabetic macroangiopathy is atherosclerosis， and the metabolism legacy effect of hyperglycemia will cause continuous damage to the large vessels. Oxidative stress is a common mechanism for diabetes and its chronic complications and it is also the basis of the metabolism legacy effect which keeps damaging the large vessels. Anti-oxidant therapy can delay the course of diabetic macroangiopathy. According to the theory of traditional Chinese medicine （TCM）， the pathogenicity of hidden pathogen is concealing， lingering， and refractory. On the basis of the syndrome and treatment of collateral diseases， vessel-collateral theory， and hidden pathogen theory of TCM， the pathological changes of diabetic macroangiopathy are summarized as pathogen concealment-accumulation of sugar and lipids leading to phlegm and blood stasis-accumulation of toxins-damage to vessels and collaterals-hardening vessels. The core pathogenesis is the hidden pathogen damaging the collaterals， and the basic pathological change is vessel hardening. The toxins of sugar， lipid， phlegm， and stasis are the pathological products and the key to be treated. According to this theory， the medicinal materials with the functions of activating blood to dredging collaterals， resolving phlegm to clearing collaterals， Promoting qi to unblocking collaterals and removing toxins to shunting collaterals can be selected for prescription. These medicinal materials can inhibit the generation of reactive oxygen species， affect the oxidase activity， and enhance the antioxidant capacity， thereby regulating the oxidative stress response， protecting the vascular endothelial function， reducing the damage of the large blood vessels， and slowing down the progression of the disease. Such therapy is of great significance in clinical practice and research， providing a new idea for the prevention and treatment of diabetic macroangiopathy.

Objective:To explore the feasibility and clinical value of artificial intelligence-assisted breast ultrasound in screening breast cancer in Tibet.Methods:Two hundred and eighty-six women who participated in breast cancer screening in Shigatse People′s Hospital from August to September in 2021 were selected. The study included four groups. Group 1, ultrasound screening by senior breast ultrasound doctors from Shanghai; Group 2: local ultrasound doctors used intelligent-assisted ultrasound equipment for screening; Group 3: local ultrasound technicians used intelligent-assisted ultrasound equipment for screening; Group 4: ultrasound screening by local ultrasound doctors. The pathological results of screening positive cases and six-month ultrasound follow-up results of negative cases were set as the gold standard.Results:Twenty-seven lesions of 21 persons were screened positive. Pathology showed that 1 case of invasive ductal carcinoma, 1 case of severe atypical hyperplasia, 6 cases of fibroadenoma, 5 cases of breast disease, 14 cases of breast hyperplasia. Two hundred and sixty-five persons were screened negative, and the results of the six-month ultrasound follow-up were still negative. The accuracy, sensitivity, and specificity of group 2 were 0.966, 1, and 0.964 respectively; The accuracy, sensitivity, and specificity of group 3 were 0.935, 0.769, and 0.943 respectively; The accuracy, sensitivity, and specificity of group 4 were 0.860, 0.308 and 0.885 respectively. The accuracy and area under the curve of groups 2 and 3 were significantly different from that of group 4 (all P<0.001), and there was no significant difference from that of group 1 ( P=0.063, P=0.055). Conclusions:Artificial intelligence-assisted breast ultrasound screening technology can effectively improve the screening efficiency of non-breast ultrasound specialists and technicians. It is very suitable to solve the problems faced by grass-roots screening in Tibet and has great social significance and clinical value.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

OBJECTIVE: To carry out genetic testing for 3 fetuses with abnormal prenatal screening. METHODS: Fetal ultrasound, karyotype analysis, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization were performed. RESULTS: Abnormalities of chromosome 22 were found with all 3 fetuses. Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region, which involved 54 OMIM genes including SHANK3 and FBLN1. Fetus 2 had a mosaicism karyotype, with 12% of cells harboring a 6.6 Mb deletion in 22q13.31q13.33, covering 48 OMIM genes such as SHANK3 and PPARA, and 5% of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes. Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21, which involved 10 OMIM genes including CECR1, CECR2 and ATP6V1E1. No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis. CONCLUSION The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication, but is also closely related to chromosome structure, gene dose and genetic environment. Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.
Chromosome Aberrations ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Fetus ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Transcription Factors ; Ultrasonography, Prenatal