ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

Ischemic stroke is a neurological disease that damages brain tissue as a result of an insufficient blood supply to the brain,due to blockage or stenosis of the brain vessels.Increasing evidence has indicated that the Wnt/β-catenin signaling pathway plays an important role in the pathophysiological response to the occurrence and development of ischemic stroke.Programmed cell death includes many forms,such as apoptosis,necrotic apoptosis,pyroptosis,autophagy,PANoptosis,and ferroptosis.In this review,we elucidate the characteristics of these different modes of cell death and their cross-talk relationships with each other,and systematically outline the role of Wnt/β-catenin signaling pathways in the intervention of different cell death modes in ischemic stroke,with the aim of providing references for future clinical and basic research studies.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Objective:To evaluate the biomechanical performance of our self-designed anatomical plate for posterolateral tibial plateau in comparison with conventional plates for treatment of posterolateral tibial plateau fractures.Methods:A novel anatomic plate for posterolateral tibial plateau was designed according to the data measured in the superior fibular capitulum and 3D CT segmentation. Twenty-four knee joints were obtained from 12 freshly frozen adult cadavers to make models of posterolateral tibial plateau fracture. The models were divided into 3 groups( n=8). In group A, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by our self-designed anatomic plate for posterolateral tibial plateau; in group B, fixation was simulated via the posterior tibial approach after autogenous iliac bone-graft by a small T-plate; in group C, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by a normal L-plate. Biomechanical tests were carried out in the 3 groups to measure the vertical displacements of split bone fragment under the vertical compression loads of 500 N, 1,000 N and 1,500 N and the maximum compression upon failure of internal fixation (compressed displacemen t=3 mm). Results:At the vertical compression loads of 500 N, 1,000 N and 1,500 N, the vertical displacements of split bone fragment showed significant differences among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P<0.05), but an insignificant difference between group A and group B ( P>0.05) though group A performed slightly better. In terms of the maximum compression upon failure of internal fixation, significant differences existed among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P< 0.05), but an insignificant difference between group A and group B ( P>0.05). Conclusions:Our self-designed anatomic plate for posterolateral tibial plateau can firmly fixate the fracture fragments of posterolateral condyle.

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Objective:To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Methods:From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Results:The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases ( r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95% CI: 0.39%, 0.54%) or 1.31% (95% CI: 1.12%, 1.50%), respectively. Conclusion:From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.

Objective:To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Methods:From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Results:The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases ( r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95% CI: 0.39%, 0.54%) or 1.31% (95% CI: 1.12%, 1.50%), respectively. Conclusion:From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.

OBJECTIVE: To explore the clinical and laboratory characteristics of 5 patients with myeloid leukemia and t(12;22)(p13;q12). METHODS: Bone marrow cells were cultured for 24 h and analyzed by standard R-banding. Rearrangement of the MN1 gene was detected by fluorescence in situ hybridization (FISH) using dual color break-apart MN1 probes. MN1-ETV6 and ETV6-MN1 fusion genes were detected by reverse transcription polymerase chain reaction (RT-PCR). And the products were subjected to direct sequencing. RESULTS: Among the 5 patients, 2 had AML-M0, 2 had AML-M4, and 1 had CMML at the initial diagnosis. t(12;22)(p13;q12) was the primary abnormality among all patients. Rearrangements of MN1 gene were detected by FISH in all patients. MN1-ETV6 and ETV6-MN1 fusion genes were detected respectively in 4 and 3 patients. CONCLUSION t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality in myeloid leukemia, and is related to poor prognosis. allo-SCT is valuable for patients with t(12;22)(p13;q12).
Chromosome Banding ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 22 ; Cytogenetics ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid ; genetics ; Oncogene Proteins, Fusion ; Translocation, Genetic

OBJECTIVETo report on clinical and laboratory features of myeloid neoplasms with double del(20q).

METHODSCytogenetic examination of bone marrow was performed on 13 cases of myeloid neophasms with double del(20q) after 24 hours of cell culture. R-banding was used to analyze the karyotypes. Interphase fluorescence in situ hybridization (FISH) was performed using dual-color probes for 20q11/20q12.

RESULTSDouble del(20q) was found to be the sole abnormality in 9 cases, double del(20q) and trisomy 9 was found in 1 case, trisomy del(20q) was found in 1 case, and sole del(20q) clone and double del(20q) clone were found to coexist in 2 cases. In 10 cases, interphase FISH showed one green and one red signal in cells with del(20q), which indicated deletion of both 20q11 and 20q12. Immunophenotyping of the leukemia cells showed positiveness for CD13 and/or CD33, CD117 in all 9 cases. Among these, co-expression of CD34 and/or HLA-DR was found in 6 cases, and coexpression of CD3 and CD7 was found in 1 case. Of the 13 cases, there were one AML-M6, nine MDS, one pure amegalokaryocye aplastic thrombocytopenia, one with normal morphology of bone marrow, and one undetermined due to dilution of the bone marrow by blood. Cytopenia were found in all cases. 9 of 13 cases died, and 4 survived with a median survival of 9 months.

CONCLUSIONDouble del(20q) is a rare but recurrent chromosomal abnormality derived from del(20q). It has unique clinical and laboratory features, and the prognosis is poor.

Aged ; Chromosome Banding ; methods ; Chromosome Deletion ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Neoplasms ; genetics

Objective:To evaluate the clinical application of vancomycin in a cancer hospital in order to promote the rational use of vancomycin. Methods:The records of 66 patients treated with vancomycin in 2015 were reviewed and analyzed in the respects of in-dications of medication, pathogenic examination, usage and dosage, course of treatment, drug combination, drug monitoring and drug utilization index(DUI). Results:Among the 66 cases, most drug use was rational, which accounted for 69. 70% with DUI of 0. 82. There were still several types of irrational drug use including no medication indications, irrational usage and dosage, too long or too short course of treatment, irrational combination and prophylactic use time. Conclusion:The application of vancomycin is basically ra-tional, while irrational phenomenon still exists. The management and supervision should be further strengthened in order to promote clinical rational drug use and ensure medication safety of patients.