Short term follow-up of unstable femoral neck fractures in young adults treated with femoral neck system and cannulated compression screws / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of femoral neck system(FNS) and three cannulated compression screws(CCS) in the treatment of unstable femoral neck fractures in young adults.@*METHODS@#The clinical data of 52 young and middle-aged patients with unstable femoral neck fractures admitted from August 2018 to August 2021 were reviewed and analyzed. All patients were divided into two groups according to the internal fixation method, 25 cases were treated with FNS fixation, 27 cases were treated with closed reduction and 3 CCS inverted triangular distribution. The operation time, incision length, intraoperative bleeding, hospitalization expenses and fracture reduction quality of two groups were recorded and compared;The patients were followed up regularly after operation. The fracture healing time, complete weight-bearing time and postoperative complications(nonunion, femoral neck shortening, femoral head necrosis) of two groups were compared. The Harris score was used to evaluate hip function 6 months after surgery.@*RESULTS@#The operation was successfully completed in both groups. The patients in FNS group had more bleeding, longer incision length and higher hospitalization cost than CCS group(P<0.01). There ware no significant difference in operation time and Garden index between two groups(P>0.05). Patients in both groups were followed up for 6 to 32 months.The fracture healing time in FNS group was less than that in CCS group, the time of complete weight bearing after surgery was earlier than that in CCS group, and the hip Harris score was higher than that in CCS group (P<0.01). There were no internal fixation fracture complications in two groups during follow-up. In the FNS group, there were 4 cases of avascular necrosis of the femoral head and 2 cases of femoral neck shortening, of which 3 cases underwent total hip replacement due to avascular necrosis of the femoral head. In the CCS group, there were 2 cases of nonunion, 9 cases of avascular necrosis of the femoral head, and 11 cases of femoral neck shortening, among which 5 cases underwent total hip replacement due to nonunion and avascular necrosis of the femoral head.@*CONCLUSION@#With simple operation, rotational stability and angular stability, FNS enables patients to start functional exercise as early as possible and reduces the incidence of postoperative complications of unstable femoral neck fracture. It is a new choice for the treatment of unstable femoral neck fracture in young adults.

Rhein Attenuates Migration of Breast Cancer MDA-MB-231 Cells Through Inhibiting Mitochondrial Fission and EMT / 世界科学技术-中医药现代化

Objective To investigate the effects of the rhein on the mitochondria fission and epithelial-mesenchymal transition(EMT)of breast cancer cells MDA-MB-231.Methods Human breast cancer cells were intervened with rhein,and the cells were divided into control group(0 μmol·L-1),low dose rhein group(100 μmol·L-1),and high dose rhein group(200 μmol·L-1).The proliferation activity of the cells was detected by CCK-8,and migrations was detected by Scratch-healing migration assay.The morphology and distribution of mitochondria were detected by transmission electron microscope,and the expression levels of Dynamin-related protein 1(Drp1),mitofusin2(Mfn2),E-cadherin,Vimentin proteins were detected by Western blot.Results Compared with control group,Rhein significantly reduced the protein expression of Drp1、Vimentin(P<0.05),and increased E-cadherin and Mfn2,thus down-regulating mitochondria fission,inhibiting cell proliferation and migration.High dose Rhein was better than low dose.Conclusion Rhein can inhibit the proliferation and migration of breast cancer cells by reducing the expression of Drp1,Vimentin and up-regulating Mfn2,E-cadherin proteins.

Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone / 中华内科杂志

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Establishment of SKH-1 mouse models of implanted B16F10 melanoma / 中华皮肤科杂志

Objective:To establish SKH-1 mouse models of subcutaneously transplanted B16F10 melanoma and of lung-metastasized B16F10 melanoma.Methods:Seven SKH-1 mice and seven C57BL/6 mice were subcutaneously inoculated with 5 × 10 6 B16F10 cells on the back, and the survival duration of mice was observed and recorded. The tumor volume was measured by using a precision vernier caliper every 3 days. Mice were considered as ethically dead when the tumor length was more than 15 mm, or when cachexia or ulceration occurred. In addition, 5 SKH-1 mice were injected with 5 × 10 6 B16F10 cells via the tail vein, and the activity, nutritional status and survival duration of the mice were observed. The mice were sacrificed after the observation, and the lungs were weighed after dissection. Histopathological examination was performed on the lungs of all mice. All the experiments were repeated 3 times. Results:On day 6 after the subcutaneous inoculation, black spots appeared at the skin inoculation site in the SKH-1 mice, and gradually developed into round black nodules, then progressed into ulcerative and hemorrhagic tumors until the death of mice, and the time to ethical death ranged from 20 to 33 days. In the C57BL/6 mice, small black nodules measuring 2 - 3 mm in length appeared at the skin inoculation site on day 4 after the subcutaneous inoculation, and the time to ethical death ranged from 12 to 18 days. The survival duration of SKH-1 mice was 26.57 ± 4.03, 27.86 ± 4.53, and 27.43 ± 5.32 days in the 3 times of experiments respectively, and there was no significant difference ( F = 0.14, P = 0.87) ; on day 27 after the subcutaneous inoculation, the tumor volume was 1 367.9 ± 150.2, 1 452.0 ± 50.1, and 1 490.3 ± 69.0 mm 3 in the 3 times of experiments respectively, and there was also no significant difference ( F = 0.92, P = 0.46). SKH-1 mice had shown decreased activity and anorexia since day 25 after tail vein injections of B16F10 cells, and dullness, emaciation, ascites and death had been observed since day 31, and the time to ethical death ranged from 31 to 40 days; multiple black nodules were observed in the lung after dissection, and the survival duration was 34.20 ± 2.58, 36.40 ± 2.60, and 34.80 ± 2.38 days in the 3 times of experiments respectively, which did not differ among the 3 times of experiments ( F = 1.01, P = 0.39) ; there was also no significant difference in the lung weight among the 3 times of experiments (156.1 ± 18.5, 164.0 ± 19.6, and 172.0 ± 17.2 mg, respectively, F = 3.18, P = 0.72). All the mice developed tumors, and histopathological examinations of subcutaneous tumor masses and lung tissues confirmed the diagnosis of melanoma. Conclusion:In this experiment, the SKH-1 mouse models of subcutaneously transplanted B16F10 melanoma and of lung-metastasized B16F10 melanoma were successfully established, which showed high tumor formation rates and favorable stability in tumor formation.

Application and effect of electronic signature verification technology in children's vaccination clinic / 公共卫生与预防医学

Objective To evaluate the application and effect of signature verification technology in children's vaccination clinics (CVC) of Jiangsu Province in 2020. Methods The signature verification data were derived from the Jiangsu Provincial Vaccination Integrated Service Management Information System, and the inquiry and registration, informed consent, vaccine traceability code scanning and observation information of children's vaccination clinics in different regions were analyzed. 210 doses of vaccination information were randomly selected from CVCs in each county, and the length of vaccination services in different regions was compared. Results During 2020, all of CVCs in Jiangsu were equipped with signature verification technology, and the signature verification rate of each vaccination sector was more than 99.90%. The length of outpatient vaccination service and overall length of stay in southern Jiangsu were slightly shorter than those in other regions. Conclusion The introduction of electronic signature verification technology in CVCs can effectively standardize the vaccination. It is necessary to expand the functions of electronic signature verification equipment, strengthen data analysis and utilization, and guide vaccination scientifically.

FOXP4 promotes proliferation of human spermatogonial stem cells / 亚洲男科学杂志(英文版)

Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.

Epidemiological and etiological analysis of two infantile cases of serogroup B epidemic cerebrospinal meningitis epidemics in Shandong Province, 2021 / 中华预防医学杂志

Two cases of epidemic situation of serogroup B meningitis in infants in Shandong Province in 2021 were investigated. Samples of cases and their close contacts were collected for isolation, culture and identification of Neisseria meningitides (Nm). The isolates were subjected to multi-locus sequence typing, outer membrane protein porA and fetA genotyping and drug sensitivity test. Two laboratory-confirmed outbreaks of serogroup B meningitis were reported from Yantai city and Linyi city. The indicated cases were infants aged 5 months and 2 months old respectively. They were not vaccinated with meningitis vaccine. Their epidemiological characteristics and clinical manifestations were similar and the prognosis was good. The same sequence type (ST) of serogroup B Nm strains as the indicated cases was detected in the samples of close family contacts, but without subsequent cases. Among them, Yantai strain was were identified as the type ST-8920, belonging to CC4821 clonal complex, and the genotypes of porA and fetA were p1.21-2, 23 and F3-1. Linyi strain was a new type, belonging to CC4821 clonal complex and the genotypes of porA and fetA were p1.20, 23 and F1-91. The above strains were resistant to penicillin, ciprofloxacin, levofloxacin and Chemitrim, and their sensitivity to cephalosporin decreased. Two cases of infant serogroup B epidemic were relatively rare in China, which were different from the epidemiological and pathogenic characteristics of other Nm serogroups in the past.

Establishment of Drug-Resistant Cell Lines of Acute Myeloid Leukemia and Correlation of Sirt1 and PGC-1α Expression Levels with Drug Resistance / 中国实验血液学杂志

OBJECTIVE@#To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance.@*METHODS@#Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot.@*RESULTS@#The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001).@*CONCLUSION@#AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.

Improving native human sperm freezing protection by using a modified vitrification method / 亚洲男科学杂志(英文版)

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.

Toxicity and Efficacy of Water-eluted Fraction from Siegesbeckiae Herba Against Human Embryonic Lung Fibroblasts / 中国实验方剂学杂志

Objective:To detect the toxicity of water-eluted fraction from Siegesbeckiae Herba （SWEF） at different concentrations against MRC-5 human embryonic lung fibroblasts and its impacts on the expression of <italic>α</italic>7 nicotinic acetylcholine receptor （<italic>α</italic>7nAChR） and inflammatory factors， so as to figure out the active components responsible for toxicity and efficacy. Method:The toxicities of SWEF at 1， 6， 10， 20， and 50 g·L^-1 against MRC-5 cells were determined by cell counting kit-8 （CCK-8） assay combined with flow cytometry and Trypan blue staining. The changes in <italic>α</italic>7nAChR expression and inflammatory factor levels before and after <italic>α</italic>7nAChR gene silencing were detected to reveal the pharmacodynamic effect of SWEF on MRC-5 cells. Result:SWEF （≥6 g·L^-1） obviously inhibited the viability of MRC-5 cells （<italic>P</italic><0.01） and promoted their apoptosis and necrosis （<italic>P</italic><0.01）， with the half-maximal inhibitory concentration （IC₅₀） being 6.03 g·L^-1. The determination of <italic>α</italic>7nAChR expression and inflammatory factor levels in MRC-5 cells showed that SWEF contained <italic>α</italic>7nAChR agonist-like substance， which enhanced <italic>α</italic>7nAChR mRNA and protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01） and decreased the inflammatory factor levels （<italic>P</italic><0.05， <italic>P</italic><0.01）. SWEF down-regulated the inflammatory factors possibly by re-regulating <italic>α</italic>7nAChR mRNA expression， exhibiting a negative correlation between them （<italic>P</italic><0.01）. Conclusion:SWEF （≥6 g·L^-1） is highly toxic to MRC-5 cells. Pharmacodynamic studies have confirmed that <italic>α</italic>7nAChR agonist-like substance contained in SWEF was responsible for the elevated <italic>α</italic>7nAChR expression and reduced inflammatory cytokines. It is inferred that excessive <italic>α</italic>7nAChR agonist-like substance may trigger the toxicity of<italic> </italic>Siegesbeckiae Herba.

Influence of sperm morphology on pregnancy outcome and offspring in / 亚洲男科学杂志(英文版)

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology (ART). However, the impact of teratozoospermia on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes and its offspring remains inconclusive. In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI, a retrospective study was conducted. This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha, China, from June 2013 to June 2018. Patients were divided into two groups based on sperm morphology: teratozoospermia and normal sperm group. The pregnancy outcome and newborn outcome were analyzed. The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF (P = 0.007), while there were no statistically significant differences between the two groups in terms of the fertilization rate, cleavage rate, implantation rate, and pregnancy rate (all P > 0.05). Additionally, teratozoospermia was associated with lower infant birth weight in multiple births after IVF. With regard to ICSI, there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups (both P > 0.05). Furthermore, no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI. Consequently, we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI, and has little impact on the resulting offspring if multiple pregnancy is avoided.

1H-NMR Metabolomic Analysis of Brain Tissue of CUMS-Induced Depressed Mice Intervened by Iridoid Part of Valerianae Jatamansi Rhizoma et Radix / 中国实验方剂学杂志

Objective:Metabolomics was used to analyze the brain tissue samples of model mice with chronic unpredictable mild stress (CUMS) depression, in order to find out the differential metabolites related to depression and to explore the possible antidepressant mechanism of iridoid part of Valerianae Jatamansi Rhizoma et Radix (IEFV). Method:Forty-two Kunming mice were randomly divided into 6 groups, including the normal group, the model group, the fluoxetine group (2.5 mg·kg-1) and the IEFV low, medium, and high dose groups (doses were 5.73, 11.47, 22.94 mg·kg-1, respectively). The behavioral and biochemical indicators of CUMS model mice were used for pharmacodynamic evaluation with IEFV and a positive drug (fluoxetine) as the intervention drugs. Then, the effect of IEFV on endogenous substances of the brain tissue in CUMS model mice were analyzed by nuclear magnetic resonance hydrogen spectrum (1H-NMR) metabolomics, and multivariate statistical analysis was used to identify the differential metabolites and to enrich the metabolic pathways involved in the differential metabolites. Result:After modeling, the immobility time of the model mice increased significantly, their sucrose preference rate and the excitatory neurotransmitters [5-hydroxytryptamine (5-HT) and norepinephrine (NE)] decreased significantly, indicating the success of modeling. The depression was relieved after IEFV administration, mainly manifested by the recovery of the immobility time, sucrose preference rate and the excitatory neurotransmitters (5-HT and NE). Principal component analysis (PCA) of endogenous metabolites in brain tissue showed that the model group could be significantly separated from the normal group, while the IEFV groups and fluoxetine group all showed a trend of deviating from the model group to the normal group, which was consistent with the behavioral results. The results of orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 16 different metabolites between the model group and the normal group, including 12 water-soluble metabolites and 4 liposoluble metabolites. Seven potential metabolism pathways were obtained through MetPA analysis, including metabolism of phenylalanine, metabolism of phenylalanine, tyrosine and tryptophan, metabolism of taurine and hypotaurine acid, metabolism of alanine, aspartic acid and glutamic acid, biosynthesis of valine, leucine and isoleucine, metabolism of D-glutamine and D-glutamate and tricarboxylic acid cycle (TCA). IEFV-high dose group could significantly recall 11 differential metabolites. Conclusion:IEFV may play an antidepressant role mainly by affecting energy metabolism, amino acid metabolism and neurotransmitter levels, which provides a reference for further study on the antidepressant mechanism of IEFV.

Mechanism Analysis of Lung Injury Induced by Water Elution Section of Siegesbeckiae Herba on Rats by 1H-NMR Metabolomics / 中国实验方剂学杂志

Objective:Metabolomics was used to analyze the dynamic changes of endogenous metabolites in serum and lung tissue of rats treated with water elution section of Siegesbeckiae Herba (SWES), and to explore the possible mechanism of lung injury and to search for the sensitive markers in serum and lung tissue. Method:SD rats were randomly divided into three groups, namely the normal group (normal saline), SWES high-dose group and SWES low-dose group (0.500, 0.125 g·kg-1·d-1). SWES was given for 4 weeks and stopped for 2 weeks. The weight and pathological examination were regarded as observation parameters. Serum and lung tissue samples were detected by nuclear magnetic resonance hydrogen spectrum (1H-NMR). The metabolites in rats were analyzed by partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Result:Lung inflammation was shown in SWES high-dose group and returned to normal after withdrawal for 2 weeks. The metabolic spectrum of SWES high-dose group was significantly different from the normal group. There were 11 metabolites were identified by 1H-NMR metabolomics, four differential metabolites were identified in serum [acetate, trimethylamine oxide (TMAO), glycine, myo-inositol] and nine differential metabolites were identified in lung tissue [lactate, acetate, phosphatidylcholine (PC), pyruvate, dimethylamine, glutamate, glycerophosphocholine (GPC), glycine, xanthine]. Lung injury was related to the disorder of pyruvate metabolism, glutamate metabolism and other pathways. Most of the metabolites in lung tissue had obviously levels of callback after drug withdrawal, which coincided with the pathological examination. Conclusion:The lung is one of the damaged organs caused by SWES, and the lung injury is reversible and may be related to energy metabolism and oxidative stress.

Reversal effect of peptide-modified chitosan tetramethylpyrazine nanoparticles on multidrug resistance in tumor cells / 中国中药杂志

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.

Adipose mesenchymal stem cells promote the function and survival of islet graft during co-transplantation / 中华器官移植杂志

Objective To explore the function and survival of islet grafts during co-transplantation with adipose mesenchymal stem cells (AMSCs) in diabetic mice .Methods After human AMSCs and islet cells were isolated ,purified and then subcutaneously co-transplanted into nude mice with diabetes mellitus . Four groups of AMSCs + islet co-transplantation , islet transplantation alone ,phosphate buffered solution (PBS) and normal control mice were designated . Islet cell activity and apoptosis/revascularization degree of islet grafts were observed by immunohistochemical double staining of insulin ,factor associated suicide (Fas) and CD31 antibody . The blood glucose and serum insulin levels of mice and the survival time of islet grafts were compared . Results The blood glucose and serum insulin levels of diabetic mice analyzed by multivariate analysis in AMSCs + islet co-transplantation group were better than those in islet transplantation alone group (P< 0 .05 ) . The mean survival time (MST ) of islet grafts was longer in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(81 .33 ± 7 .58) vs .(58 .17 ± 6 .91) days] (P<0 .05) .At Day 7 post-transplantation ,insulin staining intensity of islet grafts was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group while Fas staining intensity of islet grafts was lower .And mean microvascular density (MVD) of islet grafts per square millimeter was higher in AMSCs + islet co-transplantation group than that in islet transplantation alone group [(21 .8 ± 5 .6 ) vs . (14 .6 ± 4 .1 )] ( P< 0 .05 ) .Conclusions Co-transplantation with AMSCs may improve the function of islet grafts ,prolong its survival and promote its revascularization .

A long-term result of laparoscopic Roux-en-Y gastric bypass vs.laparoscopic sleeve gastrectomy in the treatment of obese patients with type 2 diabetes mellitus / 中华普通外科杂志

Objective To compare laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy for the treatment of obese patients with type 2 diabetes mellitus.Methods A retrospective analysis of T2DM patients with LRYGB (28 cases) and LSG (35 cases) was enrolled from Jan 2010 to Jun 2013.Results The indicator such as BMI,fasting glucose,fasting insulin,HbA1c,and insulin resistance were significantly lower in 1 year,3 years and 5 years after operation [LRYGB group:(37.3 ±3.7) kg/m2 to (32.3 ± 3.4) kg/m2 to (28.8 ± 3.0) kg/m2 to (25.5 ± 2.8) kg/m2,t =13.670,15.499,21.710,P=0.000,0.000,0.000;(8.2 ± 1.8) mmol/L to (6.0 ± 1.3) mmol/L to (5.2 ±0.9) mmol/L to (4.7±0.5) mmol/L,t =6.664,8.723,10.282,P=0.000,0.000,0.000;(32.2±17.0) μ IU/ml to (16.1 ± 12.1) μIU/ml to (8.6 ±5.2) μ IU/ml to (5.2 ±2.8) μIU/ml,t =7.453,8.218,8.687,P =0.000,0.000,0.000;(7.4％ ±0.6％) to (6.2％ ±0.7％) to (5.7％ ±0.7％) to (5.1％ ±0.6％),t =11.362,18.771,21.186,P=0.000,0.000,0.000;(12.0±7.3) to (4.6±4.3) to (2.1 ±1.7) to (1.1 ±0.7),t =6.455,7.667,8.050,P=0.000,0.000,0.000;LSG group:(39.2±5.2) kg/m2 to (34.1 ±4.5) kg/m2to (29.3±4.0) kg/m2to (25.1 ±2.3) kg/m2,t=11.676,13.680,19.161,P=0.000,0.000,0.000;(8.0±2.9) mmol/L to (5.8±1.5) mmol/L to (5.1 ±0.9) mmol/L to (4.6 ±0.5) mmoL/L,t=5.467,6.921,7.741,P=0.000,0.000,0.000;(29.1 ±25.2) μIU/ml to (16.4±10.6) μ IU/ml to (8.8±5.5) μ IU/ml to (5.5 ±2.0) μIU/ml,t =3.512,5.232,5.702,P=0.001,0.000,0.000;(7.7％ ±1.3％) to (6.3％ ±0.6％) to (5.8％ ±0.6％) to (5.2％ ±0.6％),t=8.001,10.106,11.922,P =0.000,0.000,0.000;(9.8 ±9.6) to (3.9 ±2.2) to (1.9 ±1.0) to (1.1 ± 0.4),t =3.733,4.972,5.404,P =0.001,0.000,0.000].There was no significant difference between the two groups in 1 year,3 year and 5 year post-operation (DM remission:71％ to 69％,89％ to 80％,93％ to 89％) (P ＞ 0.05).Conclusion LRYGB and LSG have the same long-term efficacy for T2DM patients.

Guiding value of ambulatory blood pressure monitoring index in clinical prevention and treatment of elderly hypertensive population / 中华疾病控制杂志

Objective To study the application value of dynamic monitoring of blood pressure in the prevention and treatment of elderly hypertension. Methods 519 hypertensive patients from December 2017 to December 2018 were monitored with ambulatory blood pressure monitoring, and were divided into the elderly group (≥60 years old, 264 cases) and the control group (<60 years old, 255 cases). The results of ambulatory blood pressure monitoring in two groups were analyzed, which inclued the circadian rhythm of blood pressure, blood pressure, pulse pressure, coefficient of variation of blood pressure, blood pressure load value, average heart rate and morning blood pressure surge. Results The incidence of abnormal circadian rhythm of ambulatory blood pressure in the elderly group was 76.5%. Compared with the control group, there were differences in the indexes of diastolic blood pressure (DBP), diastolic blood pressure load value (DBPLV), pulse pressure (PP), 24 h average heart rate (24 hAHR), systolic blood pressure coefficient of variation (SBPCV), 24 h diastolic blood pressure coefficient of variation (24 h DBPCV) and morning diastolic blood pressure surge (MDBPS) between the two groups(all P<0.05). There were differences in 24 h systolic blood pressure (24hSBP), night systolic blood pressure (nSBP), night diastolic blood pressure (nDBP), night pulse pressure (nPP), day systolic blood pressure load value (dSBPLV), ninght systolic blood pressure load value (nSBPLV), 24 h SBPCV, 24 h dDBPCV and other indicators among different blood pressure types in the elderly group (all P<0.05). Conclusion Ambulatory blood pressure monitoring indicators have important guiding value for the prevention and treatment of elderly hypertension.

Metabolism of a promising anti-tumor agent CAT3 in vitro / 药学学报

CAT3 is a promising anti-brain tumor agent that has significant anti-tumor activity on Daoy or U87MG orthotopic xenograft in nude mice. This study was carried out to investigate the metabolic profiles of CAT3 in mouse/dog/human blood and microsome as well as in humanized recombinant enzymes. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. Our findings showed that CAT3 could be hydrolyzed to active metabolite PF403 by carboxylesterase, butyrylcholinesterase and serine hydrolase in mouse/dog/ human blood. PF403 could be further metabolized to M1 oxidative dehydration product, M2 double oxidation dehydration product, M3 methylation oxidative dehydration product, M4 oxidation product and M5 demethylation product, which were mainly catalyzed by CYP1A2, 1A1, 2C9 and 3A4, and slightly by CYP2B6, 2C8, 2C19 and 2D6. Besides oxidative metabolism, PF403 also was transformed into glucuronylation metabolites GLU-PF403 by Phase II enzymes UGT1A1, 1A3 and 1A9. Taken together, the metabolism of CAT3 was a multiple enzyme catalytic reaction. These results could provide valuable information for potential enzyme-mediated DDI in clinic studies.

PLZFposc-KITpos-delineated A1-A4-differentiating spermatogonia by subset and stage detection upon Bouin fixation / 亚洲男科学杂志(英文版)

While hallmarks of rodent spermatogonia stem cell biomarkers' heterogeneity have recently been identified, their stage and subset distributions remain unclear. Furthermore, it is currently difficult to accurately identify subset-specific SSC marker distributions due to the poor nuclear morphological characteristics associated with fixation in 4% paraformaldehyde. In the present study, testicular cross-sections and whole-mount samples were Bouin fixed to optimize nuclear resolution and visualized by immunohistochemistry (IHC) and immunofluorescence (IF). The results identified an expression pattern of PLZFhighc-KITpos in A1 spermatogonia, while A2-A4-differentiating spermatogonia were PLZFlowc-KITpos. Additionally, this procedure was used to examine asymmetrically expressing GFRA1 and PLZF clones, asymmetric Apr and false clones were distinguished based on the presence or absence of TEX14, a molecular maker of intercellular bridges, despite having identical nuclear morphology and intercellular distances that were <25 μm. In conclusion, this optimized Bouin fixation procedure facilitates the accurate identification of spermatogonium subsets based on their molecular profiles and is capable of distinguishing asymmetric and false clones. Therefore, the findings presented herein will facilitate further morphological and functional analysis studies and provide further insight into spermatogonium subtypes.

Functional connectivity of the fronto-striatal circuitry in patients with bulimia nervosa based on resting-state fMRI / 中华行为医学与脑科学杂志

Objective To explore the functional connectivity (FC) of the fronto-striatal circuitry in patients with bulimia nervosa (BN) based on the resting-state fMRI and its correlation with the inhibitory function.Methods 27 medication-naive female patients with BN and 27 age-and education-matched female healthy control subjects were included in the study.All the subjects performed a stop signal task (SST) and underwent the resting-state fMRI scan,separately.The FC between striatal subregions and the frontal cortex was analyzed.Results Compared with healthy controls,FC between the right ventral rostral putamen (VRP) and the right supplementary motor areas (SMA) decreased (MNI coordinate:x =3,y =-15,z =51,K =27) in patients with BN.And the FC was also decreased between the right VRP and premotor area(PM) (MNI coordinate:x =27,y =0,z =57,K =44).FC between bilateral dorsal caudal putamen (DCP) (MNI coordinate:x=21,y=-6,z=48,K=43) and the right PM(MNI coordinate:x=21,y=-12,z=57,K=24) was decreased in patients with BN (P＜0.05,Alphasim corrected,voxel P＜0.005,clusters ≥ 20 voxels).FC between the right VRP and right SMA was negatively correlated with the stop signal reaction time (SSRT) in patients with BN (r=-0.595,P=0.004).The FC between right DCP and right PM was positively correlated with the impulsivity regulation subscale scores of the Eating Disorder Inventory-Ⅱ in patients with BN(r=0.483,P=0.023).Conclusion There is disrupted FC between the striatum and motor cortex in medication-naive female patients with BN based on resting-state fMRI,which may be related to impaired inhibitory control in patients with BN.