Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

OBJECTIVE: To investigate the effect of interference of CTPS gene on toosendanin-induced apoptosis of gastric cancer MKN-45 cells. METHODS: Bioinformatic analysis was used to analyze CTPS gene expression in human gastric cancer tissues and the overall survival of gastric cancer patients with high CTPS gene expression. Human gastric cancer MKN-45 cells were transfected with a short hairpin interfering RNA targeting CTPS gene, and 48 h later, qRT-PCR and Western blotting were used to detect cellular expression CTPS at both the mRNA and protein levels. MKN-45 cells with CTPS knockdown were treated with 80 nmol/L toosendanin for 48 h, and the cell viability was assessed with MTT assay; the cell morphology was observed using laser confocal microscope, and the expression of γH2AX was detected with immunofluorescence assay. RESULTS: Bioinformatic analysis suggested that CTPS was highly expressed in human gastric cancer tissues, and gastric cancer patients with high CTPS gene expression had a shorter overall survival. MKN-45 cells transfected with Sh-CTPS interference vector showed significantly lowered cell survival rate (P < 0.01) with obvious cell shrinkage, irregular morphology, typical apoptotic changes, and increased cell apoptosis rate (P < 0.05). Treatment of the transfected cells with 80 nmol/L toosendanin for 48 h resulted in further reduction of the cell survival rate (P < 0.001), and the cells showed an increased apoptotic rate (P < 0.05) with appearance of apoptotic bodies. CONCLUSION Interference of CTPS gene can promote TSN-induced apoptosis of gastric cancer MKN-45 cells.
Apoptosis ; Cell Line, Tumor ; Humans ; RNA, Small Interfering/metabolism* ; Silanes ; Stomach Neoplasms/metabolism* ; Triterpenes

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.
Adult ; Aged ; Aged, 80 and over ; Anemia, Macrocytic ; Humans ; Lenalidomide ; Middle Aged ; Myelodysplastic Syndromes ; Retrospective Studies ; Thalidomide

OBJECTIVETo construct a recombinant adenovirus expression vector containing the anti-oncogene PTEN and to investigate the effects of the PTEN gene on the proliferation of prostate cancer PC-3 cells and the expressions of cyclin D1 and p21 in the PC-3 cells.

METHODSThe PTEN gene was amplified from the rat hippocampus by RT-PCR and cloned into the shuttle plasmid pEN-TR2A. The plasmids were constructed and amplified in 293A cells. Prostate cancer PC-3 cells were cultured in vitro and infected with the adenoviral vector carrying the PTEN gene (Ad-PTEN). The up-regulation of the PTEN protein was measured by indirect immuno-fluorescence assay; the expressions of PTEN, cyclin D1 and p21 in the cells infected with Ad-PTEN and Ad-LacZ were determined by

RESULTSThe Western blot; and the effect of PTEN on the cell proliferation was detected by MTT assay and plate colony formation. recombinant adenoviral vector Ad-PTEN was successfully constructed. Western blot showed a significantly increased expression of the PTEN protein in the PC-3 cells infected with Ad-PTIEN (0.215 +/-0.065) as compared with that in the control ([0.052 +/-0.009], t = 4. 30, P <0.05) and the Ad-LacZ group ( [0. 056 +/- 0.008 ] , t =4.21, P <0.05). The expression of cyclin D1 was significantly lower in the Ad-PTEN-infected PC-3 cells (0. 256 +/- 0. 072) than in the control ( [0. 502 +/- 0. 087 ], t = 3.77, P < 0.05) and the Ad-LacZ group ([0.498 +/-0.081] , t =3.87, P <0.05), while the expression of p21 remarkably higher in the Ad-PTEN-infected PC-3 cells (0.589 +/-0. 076) than in the control ([0. 146 +/-0.026] , t = 9.55, P<0. 01) and the Ad-LacZ group ([0. 163 +/-0. 024] , t = 9.26, P <0.01). Ad-PTEN significantly inhibited the growth of the PC-3 cells (21.98%) at 48 h (t = 6.80, P <0.01). The colony formation rate of the PC-3 cells was (37.4 +/-4. 18)% in the Ad-PTEN group, significantly lower than (54.9 +/-4.81)% in the control (t =4.76, P<0.01) and (56.5 +/- 5.42)% in the Ad-LacZ group (t=4.83, P<0.01).

CONCLUSIONThe expression of PTEN induced by Ad-PTEN can significantly inhibit the proliferation of PC-3 cells, down-regulate the expression of cyclin D1, and up-regulate the expression of p21.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Male ; PTEN Phosphohydrolase ; genetics ; Prostatic Neoplasms ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

Objective To study and compare biomechanical properties of a newly developed magnesium AZ31B alloy intramedullary nail (AZ31B) with that of imported Poly-L-lactic acid intramedullary nail (PLLA) and pure titanium rib plate (TPRP), so as to provide scientific evidences for better internal fixation in clinical operation. Methods Forty fresh adult ribs were used and divided into 4 groups randomly. Three groups were made lateral rib fracture in midaxillary line and fixed by AZ31B, PLLA and TPRP, respectively, while the group with normal ribs was used as control. Biomechanical properties of specimens in each group were measured and tested using experimental stress analysis. Results (1) Three-point bending strength of internal fixation with AZ31B was close to that of control group (P>0.05), but significantly different to that of TPRP group and PTRP group (P<0.05); (2) No significant differences in torsional strength were found between AZ31B group, PTRP group and control group (P>0.05), and the torsional strength of both AZ31B and PTRP was superior to that of PLLA (P<0.05). Conclusions The internal fixation with AZ31B is an ideal mode for treating rib fracture since AZ31B has larger flexural strength than PLLA and TPRP, and its torsional strength was close to PTRP and normal ribs. This study provides some support for future research on biomechanical properties of AZ31B.

BACKGROUNDAlcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology.

METHODSA genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans.

RESULTSSeveral genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51 × 10(-8)). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption.

CONCLUSIONThe evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.

Adult ; Aged ; Alcohol Drinking ; genetics ; Blood Proteins ; Cytokines ; Female ; Genome-Wide Association Study ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proteins ; genetics ; Receptors, Cytokine ; genetics

The occurrence of foreign body is uncommon in youths and adults. We report here a case of 16-year-old boy who inhaled a foreign body which was overlooked for 6 months. The patient suffered productive cough and received antibiotic treatment for 10 days. But the symptoms did not improve. Chest radiography and CT scan revealed a 1-cm-long needle-like foreign object in the right inferior lobar bronchus. Wedge resection of lung was finally performed because of severe hemorrhage caused by prior bronchoscopy.
Adolescent ; Bronchoscopy ; Foreign Bodies ; diagnostic imaging ; surgery ; Humans ; Lung ; diagnostic imaging ; surgery ; Male ; Radiography

OBJECTIVETo investigate the effects of intraprostatic injection of botulinum toxin A (BTX-A) on benign prostate hyperplasia (BPH) in rats.

METHODSModels of BPH were established in adult male Sprague-Dawley rats by injection of testosterone propionate, and then divided into three BTX-A groups, injected with BTX-A into the ventral prostate at the doses of 5 U, 10 U and 20 U, a negative control group, injected with saline only, and a sham operation group, with 12 in each. The prostates of the animals were harvested at 2 or 4 weeks after the injection, their volumes and weights measured, histological changes examined by HE staining, and glandular and interstitial areas semi-quantified by the image analysis system.

RESULTSTwo rats died in the 20 U group within 3 days after BTX-A injection. Compared with the saline group, the 5 U, 10 U and 20 U BTX-A groups showed significant decreases in prostatic volume (P < 0.01, 0.01 and 0.05), weight, and glandular and interstitial areas as well as atrophic epithelia in the glandular tube at 2 weeks. These changes were lessened at 4 weeks, especially in the 5 U group.

CONCLUSIONIntraprostatic injection of BTX-A induces obvious atrophy and histological changes of the prostate, but meanwhile may potentially result in death at a large dose.

Animals ; Botulinum Toxins, Type A ; administration & dosage ; therapeutic use ; toxicity ; Male ; Prostate ; drug effects ; pathology ; Prostatic Hyperplasia ; drug therapy ; pathology ; Rats ; Rats, Sprague-Dawley

Objective To learn the spatial and temporal patterns of primary syphilis and secondary syphilis in Shenzhen and to provide evidence for carrying out further research on syphilis.Methods Primary syphilis and secondary syphilis cases among residents in Shenzhen between 2005and 2009(n=11 303) were geocoded at street office level (n=55) based on residence at the time of diagnosis. Both spatial and space-time scan statistics were used to identify clusters of street office by using SaTScan software. Results In the purely spatial analyses, clusters were seen in the junction of the Baoan district and Nanshan district (Xinan, Xixiang, Nanshan and Nantou street office) and in the region near Hong Kong (Dongmen, Shekou, and Futian street office), as well as in the other streets where entertainment industry was relatively developed (Longhua, Huafu, Huangbei and Cuizu street office). The clusters had not changed much in the first four years, but nine clusters appeared in 2009.Annually, the most likely clusters were located in Longhua (2005, P≤0.001, RR=3.34), Bamboo (2006, P≤0.001, RR=9.59), Huafu (2007, 2008 years, P≤0.001, RR values were 4.18 and 4.75)and Cuizu (2009, P≤0.001, RR=8.02). In the space-time scan analysis, we found 16 significant clusters, which were similar to the pure spatial analyses. However, regional difference were also found, with the most likely cluster was the Guiyuan street office in 2006. Conclusion Spatial and space-time scan statistics seemed to be effective ways in describing the circular disease clusters. We have had a better understanding on spatial and temporal patterns of primary syphilis and secondary syphilis in Shenzhen through spatial and space-time scan statistics of syphilis surveillance data in the recent years. The changes of spatial and temporal patterns of primary syphilis and secondary syphilis were also described by SaTScan software, which also provided useful reference for the preventive strategies on sexually transmitted diseases as well as on HIV. Useful information was also provided for financial investment and cost-effective studies.

BACKGROUNDThe University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution.

METHODSA series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied.

RESULTSThere was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22 - 31 hours were transplanted successfully and the mean renal function recovery time was (3.83 +/- 1.68) days.

CONCLUSIONSCZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.

Adenosine ; pharmacology ; Allopurinol ; pharmacology ; Animals ; China ; Glutathione ; pharmacology ; Heart ; drug effects ; physiology ; Heart Transplantation ; methods ; Insulin ; pharmacology ; Intestine, Small ; drug effects ; physiology ; Kidney ; drug effects ; physiology ; Kidney Transplantation ; methods ; Liver ; drug effects ; physiology ; Liver Transplantation ; methods ; Lung ; drug effects ; physiology ; Lung Transplantation ; methods ; Male ; Organ Preservation ; economics ; methods ; Organ Preservation Solutions ; pharmacology ; Pancreas ; drug effects ; physiology ; Pancreas Transplantation ; methods ; Pharmaceutical Solutions ; pharmacology ; Rabbits ; Raffinose ; pharmacology ; Testis ; drug effects ; physiology