[Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors].

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Maintenance of cellular annexin A1 level is essential for PI3K/AKT/mTOR-mediated proliferation of pancreatic beta cells.

Annexin A1 (AnxA1, also known as lipocortin-1), is a calcium-dependent phospholipid binding protein with diverse functions. Previous studies have indicated that AnxA1 is associated with age-related ß-cell dysfunction and aging, which lead to decreased ß-cell proliferation capacity. However, it has been uncertain whether AnxA1 affects the proliferation of pancreatic beta (ß) cells. In the present study, we reduced AnxA1 expression in the MIN6 islet ß-cell line using small interfering RNA (AnxA1-siRNA), then measured cell cycle distribution and cellular proliferation. We also measured the expression levels of cell cycle-related proteins such as cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2) by Western blot analysis. We investigated the phosphatidylinositol 3-kinase (PI3K)/ serine/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway to explore the potential mechanism underlying the observed effects. Knockdown of AnxA1 expression using siRNA reduced the rates of MIN6 cell proliferation. The proportions of cells in S and G2/M phases also decreased upon inhibition of AnxA1. Moreover, AnxA1 protein expression in MIN6 cells was positively related to the protein levels of cyclin D1, cyclin E, and CDK2. Activation of the PI3K/Akt/mTOR signaling pathway by AnxA1 may be involved in the signaling cascade to regulate cell proliferation. This study identified a positive correlation between AnxA1 protein and pancreatic ß-cell proliferation. AnxA1 protein expression might affect the proliferation of MIN6 cells via regulation of cyclin D1, cyclin E, and CDK2 proteins, as well as the PI3K/Akt/mTOR signaling pathway.

[Clinical analysis of 314 children with maxillofacial fracture].

A total of three hundred and fourteen patients with maxillofacial fracture under 14 years old were treated at Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University from October 2010 to October 2017 were collected and retrospective analysis was conducted. Age, gender, injury factors, type of fracture, associated injuries and treatment has been analysed. There were 196 male and 118 female. The most common injury factor was fall (148 cases), accounting for 47.1% of all patients. The most common fracture type was mandible fracture (221 cases). Children are not very cooperative with clinical examination, which often leading to misdiagnosis. Age, gender, fracture injury factors, comorbidity and treatment were analyzed to provide the reference for the prevention, diagnosis and treatment.

[Application of pegylated recombinant human granulocyte colony-stimulating factor to prevent chemotherapy-induced neutropenia in patients with lymphoma: a prospective, multicenter, open-label clinical trial].

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

[Correlation of serum sex hormone levels with metabolic syndrome in elderly men].

OBJECTIVE: To investigate the relationship between sex hormones and metabolic syndrome (MS), as well as its components in elderly men. METHODS: 1 505 elderly men (≥60 years old, mean age 75.4±9.7 years old) who participated in a routine health screening examination in PLA general hospital from May to June in 2012 were enrolled in this cross-sectional study. Serum lipids, glucose and sex hormones were measured along with body height, weight and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. The correlation of serum sex hormones with the presence of MS and its components were analyzed. RESULTS: The prevalence of MS was 21.7% (326/1 505) in this study. Elderly men with MS had lower levels of sex hormone-binding globulin (SHBG), total testosterone (TT), FT and BT than those without MS. The levels of SHBG, TT, FT and BT were significantly lower in the overweight/obesity group, hyperglycemia group and dyslipidemia group than those in the respective control groups (P<0.05). Logistic regression analysis showed that the SHBG level was an independent risk factor for MS in elderly men(OR=0.977, 95%CI: 0.964-0.989, P<0.001), while the levels of TT, FT and BT were not associated with MS. The prevalence of MS gradually increased with decreasing of SHBG values (P<0.001). When comparing subjects in the lowest and highest quartile of SHBG, the former group demonstrated a 2.13-fold increase in the odds ratio for MS after adjusting for age, smoking, drinking and other sex hormone indices. CONCLUSION: In elderly men, lower SHBG level, not TT, FT or BT may be an independent predictor for the prevalence of MS, in which the mechanism requires further studies.

Prevalence, characteristics and natural history of cold intolerance after the reverse digital artery flap.

UNLABELLED: This retrospective study was designed to investigate the prevalence, characteristics and natural history of cold intolerance after the use of the reverse digital artery flap. A total of 123 patients were treated between 2010 and 2013. After excluding patients who were lost to follow-up, 87 patients were studied. The mean follow-up time was 34 months (range 14-61). Cold intolerance occurred in 60% (52) of patients after the reverse digital artery flap procedure. The condition improved in only 15% (8) of the patients. Significant differences were observed in the age and the specific digit involved between the groups with and without cold intolerance. There was a lower incidence in younger patients, and the ring finger group showed a lower incidence than in other fingers. Furthermore, the Cold Intolerance Symptom Severity score was positively correlated with the temperature at which cold intolerance was triggered. LEVEL OF EVIDENCE: IV.

Comparative study of functional and aesthetically outcomes of reverse digital artery and reverse dorsal homodigital island flaps for fingertip repair.

UNLABELLED: This retrospective study was designed to compare functional and cosmetic outcomes of the reverse digital artery island flap and reverse dorsal homodigital island flap in fingertip repair. A total of 23 patients were followed for 24 to 30 months. The reverse digital artery island flap was used in 12 patients, and reverse dorsal homodigital island flap in another 11 patients. Flap sensibility was assessed using the Semmes-Weinstein monofilament test and static 2-point discrimination test. Patient satisfaction, active motion of the finger joints, complications and cold intolerance were evaluated. The static 2-point discrimination and Michigan Hand Outcomes Questionnaire (appearance) of the fingers treated with a reverse digital artery flap were significantly better than those with a reverse dorsal homodigital flap. The static 2-point discrimination of the skin-grafted donor sides after dorsal homodigital flap were poorer than that in the contralateral finger. No significant differences were found between the two flaps for pressure or touch sensibility, active ranges of digital motion, complications and cold intolerance. LEVEL OF EVIDENCE: III.

Reverse Dorsoradial Flaps for Thumb Coverage Show Increased Sensory Recovery with Smaller Flap Sizes.

BACKGROUND: Reverse homodigital dorsoradial (RHD) flap has been developed to repair soft-tissue defects of the thumb. However, few articles have reported this flap with long-term follow-up. This retrospective study was designed to evaluate the RHD flap and investigate factors affecting sensory recovery. METHODS: From February 2010 to February 2011, 19 patients were treated consecutively with RHD flap without neurorrhaphy. At final follow-up, flap sensibility was assessed by Semmes-Weinstein (SW) monofilament, moving two-point discrimination (M-2PD), and static two-point discrimination (S-2PD) tests. Patient satisfaction, active range-of-motion of the joints, patient complications, and cold intolerance severity score questionnaire were sequentially evaluated. The patients were divided into two groups based on the S-2PD results and another two groups based on flap size. RESULTS: The mean SW monofilament sensitivity and M-2PD and S-2PD scores on the flap were 4.01 g and 9.26 mm, and 10.63 mm, respectively. Highly positive correlations existed between the flap size and the M-2PD and S-2PD scores. Moreover, in the respective groups based on S-2PD scores and flap size, no statistical difference was found among age, sex, and follow-up time, but the flap size and S-2PD scores were statistically different. CONCLUSIONS: RHD flap without neurorrhaphy is a recommendable technique for relatively small-sized thumb-defect reconstruction, which can achieve a satisfactory sensory recovery.

Genetic basis of type 2 diabetes--recommendations based on meta-analysis.

OBJECTIVE: Despite intensive effort to understand the genetic basis of type 2 diabetes, only a few genes responsible for relatively rare monogenic and syndromic subsets of diabetes are known; however, gene(s) responsible for genetic predispositions to common type 2 diabetes are unknown. The current study was obtained a better understanding of the genetic architecture of type 2 diabetes. MATERIALS AND METHODS: Comprehensive literature search was performed and the extracted data was analyzed. The proportion of variance explained by validated genetic factors for a range of metabolic quantitative traits was analyzed. RESULTS: A fully elucidated landscape of type 2 diabetes genetics may well depict perhaps a hundred or more common variants individually with low impact on disease. CONCLUSIONS: Every individual harbors a combination of different risk alleles and only special compilations of these variants in combination with other genetic and non-genetic components will likely lead to disease.

Diabetes mellitus and dementia - a systematic review and meta-analysis.

OBJECTIVES: Diabetes mellitus and dementia, two of the most common disorders in the elderly, are posing a tremendous burden on public health in the society. Moreover, the absolute number and the proportion of older people who are affected by diabetes, borderline diabetes and dementia are expected to further increase over the next few decades. The aim of this study was to determine if a relationship existed between type 2 diabetes and dementia by performing a meta-analysis of published cross-sectional and prospective studies. MATERIALS AND METHODS: Comprehensive literature search was performed and the extracted data was analyzed. RESULTS: Our findings highlight the need to detect borderline diabetes and undiagnosed diabetes in order to effectively prevent dementia, as previous studies have shown that prediabetes and diabetes could be improved by interventions addressed towards lifestyle changes and antidiabetic treatment. CONCLUSIONS: As far as clinical practice is concerned, it is important to bear in mind that prevention, timely diagnosis, and the optimum treatment of diabetes and borderline diabetes may help to reduce the occurrence of dementia.

The MEK1/2 inhibitor U0126 reverses imatinib resistance through down-regulating activation of Lyn/ERK signaling pathway in imatinib-resistant K562R leukemia cells.

Chronic myelogenous leukemia (CML) is triggered by the constitutively activated BCR-ABL oncoprotein and multiple downstream signaling pathways, including the Raf/MEK/ERK, Akt/mTOR, SRC, and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for CML. However, the development of imatinib resistance has become a new challenge for CML treatment. Here, we investigated the expression levels of the signaling pathways to explore the cause of imatinib resistance and seek new reversing drugs. Our results showed that abnormal activation of the BCR-ABL-independent Lyn/ERK signaling pathway was involved in imatinib-resistance of K562R cells. Furthermore, p-Lyn and p-ERK were up-regulated after treatment with imatinib alone. However, U0126, a MEK1/2 inhibitor, could counteract the up-regulation induced by imatinib, and the combination of imatinib and U0126 could overcome the resistance to imatinib in K562R cells. In conclusion, our studies suggest that the combination of imatinib and an inhibitor of the ERK signaling pathway may be effective in imatinib-resistant CML patients.

Efficient detection of the V600E mutation of the BRAF gene in papillary thyroid carcinoma using multiplex allele-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography.

Mutations in the V-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) play an important role in the pathogenesis of papillary thyroid cancer (PTC). In this study, a BRAF V600E mutation was detected in formalin-fixed and paraffin-embedded PTC samples using multiplex allele-specific polymerase chain reaction and denaturing high-performance liquid chromatography. The sensitivity of the assays was validated in two cell lines, K1 and RO82-W-1, which were respectively positive and negative for the mutation. The method enabled detection of very low concentrations (~1%) of the mutation, with positive findings obtained in 119 of the 187 samples (63.6%). The mutation was not detected in 20 cases of benign thyroid diseases. The presence of the mutation was significantly associated with ages >45 years, the tumor-nodes-metastasis stage, region of metastasis, and clinical outcome (P < 0.05). Although no correlation was found between the mutation and lymph node metastasis, the proportions of patients carrying a mutation differed significantly between central and lateral cervical lymph node metastasis (P < 0.05). Multivariate logistic regression analysis also indicated the presence of mutation, tumor size, and cervical lymph node metastasis to be independent predictors for recurrence and distant metastasis. We conclude that a high proportion of PTC cases likely harbors the BRAF V600E mutation. This mutation can be used as an independent factor for predicting the recurrence and distal metastasis of PTC tumors.

Comparison of three concentrations of simplex lidocaine in local anesthesia for inguinal hernia mesh-repairs.

PURPOSE: The aim of the present randomized clinical study was to assess the efficacy of simplex lidocaine in local anesthesia for inguinal hernia mesh-repairs, compare analgesia of three different concentrations of lidocaine, and explore use of lower concentrations of lidocaine in local anesthesia for inguinal hernia mesh-repairs. METHODS: A total of 102 consecutive patients undergoing inguinal hernia repairs were randomized to three groups: group A (n = 34) received solution with a lidocaine concentration of 8 mg/mL, group B (n = 34) received a lidocaine concentration of 5 mg/mL, and in group C (n = 34) the lidocaine level was reduced to 3.3 mg/mL. Intraoperative pain and pain at 24 h and 48 h postoperatively were assessed by means of a visual analogue scale. Volume and doses of lidocaine used in local anesthesia were strictly recorded. RESULTS: The efficacy of simplex lidocaine in local anesthesia for inguinal hernia mesh-repairs was excellent, no patient required conversion to general anesthesia. The mean pain scores were not significantly different among the three groups. CONCLUSIONS: The local anesthesia technique was good with lidocaine alone in local anesthesia for inguinal hernia mesh-repairs. A concentration of 3.3 mg/mL lidocaine provided similar analgesia as 5 or 8 mg/mL lidocaine.

Medial sural artery perforator flap for repair of the hand.

We report our experience of using the medial sural artery perforator flap in the reconstruction of soft tissue defects in the hand in seven cases with 1 to 2 year follow-up. The flap is harvested from the posteromedial aspect of the leg, just below the knee and superficial to the medial head of the gastrocnemius muscle. It is based on the perforator arteries and veins supplied by the medial sural artery. The flaps ranged in size from 14 x 10 cm to 8 x 6 cm. The donor area was closed directly or by a skin graft. All but one flap survived. The cosmetic results were satisfactory and without apparent bulkiness. Similarity of colour and thickness of the donor and recipient sites are advantages. We feel that this new flap is a satisfactory option for use in the hand, particularly for extended soft tissue defects on the dorsal hand.

Overexpression of Cripto and its prognostic significance in breast cancer: a study with long-term survival.

INTRODUCTION: Cripto is a founding member of the EGF-CFC family, and plays an important role in tumourigenesis, tumour cell proliferation and migration. We aimed to determine the significance of Cripto expression on the survival of patients with breast cancer. METHODS: Immunohistochemical detection of Cripto was performed by using mAb C13 on 120 formalin-fixed paraffin-embedded breast tumour specimens in tissue microarrays. This cohort comprises a series of 120 patients with primary operable breast cancer diagnosed between 1989 and 1995, retrieved from the Concord Repatriation General Hospital breast carcinoma database. RESULTS: Using a cutoff value of 80%, Cripto overexpressed in 57 of the 120 (47.5%) patients. We found significant associations between overexpression of Cripto and the Nottingham Prognostic Index (NPI, p<0.01), histological grade (p<0.01), pathological tumour type (p=0.04), PR (p=0.02) as well as Ki-67 (p=0.02). Univariate analysis reveals that there is a significant correlation between overexpression of Cripto and survival (p=0.0003). Cox regression analysis indicates that the overexpression of Cripto is an independent prognostic factor in breast cancer (HR 2.79, 95%CI 1.20-6.50). CONCLUSION: The unique epitope recognized by mAb C13 is overexpressed on breast tumour tissues. In this series of invasive breast cancers, overexpression of Cripto was more often found in high grade and poor prognosis tumours compared to low grade and good prognosis breast cancers. Moreover, overexpression of Cripto was significantly associated with decreased patient survival.

First isolation of Xanthomonas campestris from the blood of a Chinese woman.

Xanthomonas campestris isolated from the blood of a patient with a fever was first reported. Xanthomonas campestris is a bacterium that can cause black rot of some vegetables, such as rape. Chinese cabbage, etc. Human infection due to X. campestris has not been reported so far. The characteristics of this organism, including morphology, staining, physiology and biochemistry were studied. We believe that X. campestris is also one of the opportunistic pathogens, which can infect compromised host.