[The effects and mechanisms of Gefitinib on airway inflammation and airway remodeling in C57BL/6 mice with asthma].

Objective: To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice, and to analyze its possible mechanisms. Methods: Male C57BL/6 mice, aged 6-8 weeks, were randomly assigned into five groups: Group A (control group), Group B (asthma group), Group C (asthma+20 mg/kg gefitinib group), Group D (asthma+40 mg/kg gefitinib group), and Group E (40 mg/kg gefitinib group), with seven mice per group. Mice were sensitized by intraperitoneal injection of a mixture of 0.2 ml solution containing OVA and Al(OH)3 [20 µg OVA+2 mg Al(OH)3 dissolved in 0.2 ml of physiological saline] at Day 0 and 14. Starting from Day 25 to 31, Group B, C, and D were challenged with nebulization of 1% OVA solution (8 ml) to induce asthma, once a day for approximately 40 minutes, with continuous aerosolization for 7 days. Group C and D were given 0.2 ml of Gefitinib dissolved in 0.5% carboxymethylcellulose sodium (CMCNa) by gavage half an hour before challenging, and Group E was simultaneously given with 0.2 ml of Gefitinib dissolved in 0.5% CMCNa only. Group A and B were given an equivalent volume of 0.5% CMCNa by gavage. After 24 h of final challenge, the bronchoalveolar lavage fluid (BALF) was prepared for the determination of total cell count and eosinophil count. The levels of total immune globulin E (IgE) in serum and interleukin (IL)-4, IL-5 and IL-13 in BALF and lung tissue homogenates were measured by ELISA. The mRNA expression levels of IL-4, IL-5, IL-13 in lung were measured. Immunohistochemistry and Western blot experiments were used to detect the expression levels of EGFR in lung tissues. Results: In Group B, the level of total IgE in serum, total cell count, eosinophil count, the levels of IL-4, IL-5, IL-13 in BALF and the phosphorylation of EGFR and its downstream activation in lung were higher than those in Group A (all P<0.05). The levels of total IgE in serum [(261.32±44.38) ng/ml, (194.09±52.39) ng/ml vs (1 023.70±105.51) ng/ml], total cell count [(23.70±4.08)×105/ml, (14.92±4.06)×105/ml vs (35.36±6.30)×105/ml], eosinophil count [(108.00±13.69)×104/ml, (67.00±17.28)×104/ml vs (147.86±20.06)×104/ml], IL-4 [(36.42±4.48) pg/ml, (30.45±8.12) pg/ml vs (58.72±7.17) pg/ml], IL-5 [(16.20±4.62) pg/ml, (13.38±5.14) pg/ml vs (23.46±5.38) pg/ml], IL-13 [(18.45±7.28) pg/ml, (14.33±7.70) pg/ml vs (104.12±24.66) pg/ml] in BALF of Group C and D were lower than those in Group B (all P<0.05). The levels of IL-4, IL-5, and IL-13 as well as their mRNA levels in the lung tissue of Group C and D were lower than those in Group B (all P<0.05). In Group C and D, the positive expression rate of phosphorylated epidermal growth factor receptor (p-EGFR) in lung tissue [(40.53±6.80)%, (23.60±4.42)% vs (70.78±5.36)%], p-EGFR/EGFR (61.68±7.48, 51.13±5.19 vs 105.90±11.66), phosphorylated extracellular regulated protein kinase (p-Erk)/extracellular regulated protein kinase (Erk) (75.28±7.11, 47.54±4.83 vs 98.76±4.71), and phosphorylated protein kinase B (p-Akt)/protein kinase B (Akt) (96.24±5.40, 68.52±2.73 vs 103.30±4.52) was lower than those of Group B (all P<0.05). There was no statistically significant difference in the relevant indicators between Group A and E (all P>0.05). Conclusion: Gefitinib may alleviate airway inflammation and airway remodeling in asthmatic mice by inhibiting EGFR phosphorylation and affecting the activation of downstream Erk and Akt.

Resveratrol promotes bone mass in ovariectomized rats and the SIRT1 rs7896005 SNP is associated with bone mass in women during perimenopause and early postmenopause.

OBJECTIVE: This study aimed to examine the effects of SIRT1 agonist resveratrol on bone mass in ovariectomized (OVX) rats and the SIRT1 single-nucleotide polymorphism (SNP) rs7896005 on bone mass in women during menopause and early postmenopause. METHODS: An animal experiment was conducted on rats that were sham-operated (SHAM), OVX or OVX and different administered doses of resveratrol. Serum markers and femur microstructure and staining were assessed. A cross-sectional study was conducted in women undergoing menopause. SIRT1 protein and SIRT1 SNP rs7896005 were evaluated. RESULTS: OVX rats administered resveratrol, especially high doses, showed lower bone loss than OVX rats. Serum osteoprotegerin (OPG) and femur SIRT1, ß-catenin and bone mineral density (BMD) were significantly increased, whereas receptor activator of NF-κB ligand (RANKL) was significantly decreased. Serum SIRT1 levels were significantly lower in women with low bone mass (p < 0.01). Women with the CA genotype of rs7896005 had lower bone mass than those with the CC genotype. The A allele showed a significant negative effect on bone loss risk (odds ratio = 3.48; p = 0.025). CONCLUSIONS: Resveratrol stimulated SIRT1 expression and Wnt/ß-catenin signaling to promote bone mass in rat femurs. Among women in perimenopause and early postmenopause, SIRT1 protected bone mass, and the A allele of SIRT1 rs7896005 was a risk factor for reduced bone mass.

Development and validation of risk prediction models for stroke and mortality among patients with type 2 diabetes in northern China.

BACKGROUND: Stroke is one of the leading causes of disability and mortality in patients with type 2 diabetes mellitus (T2DM). Risk models have been developed for predicting stroke and stroke-associated mortality among patients with T2DM. Here, we evaluated risk factors of stroke for individualized prevention measures in patients with T2DM in northern China. METHODS: In the community-based Tianjin Chronic Disease Cohort study, 58,042 patients were enrolled between January 2014 and December 2019. We used multiple imputation (MI) to impute missing variables and univariate and multivariate Cox's proportional hazard regression to screen risk factors of stroke. Furthermore, we established and validated first-ever prediction models for stroke (Model 1 and Model 2) and death from stroke (Model 3) and evaluated their performance. RESULTS: In the derivation and validation groups, the area under the curves (AUCs) of Models 1-3 was better at 5 years than at 8 years. The Harrell's C-index for all models was above 0.7. All models had good calibration, discrimination, and clinical net benefit. Sensitivity analysis using the MI dataset indicated that all models had good and stable prediction performance. CONCLUSION: In this study, we developed and validated first-ever risk prediction models for stroke and death from stroke in patients with T2DM, with good discrimination and calibration observed in all models. Based on lifestyle, demographic characteristics, and laboratory examination, these models could provide multidimensional management and individualized risk assessment. However, the models developed here may only be applicable to Han Chinese.

[Construction and analysis of functional network of hemi-brain in patients with brain tumors before and after anesthesia based on resting-state functional magnetic resonance imaging].

Objective: To construct and analyze the functional network changes of hemi-brain in patients with brain tumor before and after anesthesia by using resting state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 18 right-handed patients were prospectively included (6 males and 12 females). The patients underwent glioma resection in Peking University International Hospital from December 2018 to December 2021, and age ranged from 20 to 65 (45.1±13.6) years, with American Society of Anesthesiologists (ASA) grade of Ⅰ-Ⅱ. MRI scans were performed while the patient was awake and at the depth of surgical anesthesia. The functional network of healthy lateral brain was constructed and analyzed by means of graph theory, and its global and local topological properties were calculated. Global topology attributes included global efficiency (Eg), local efficiency (Eloc), clustering parameters (Cp), length parameter of shortest path (Lp), and small world (SW). Topology attributes of nodes included node degree (ND), node efficiency (NE) and between centrality (BC). The global and nodal topological properties of the hemi-brain network were compared between patients with different hemispherical space occupying under wakefulness and anesthesia. Results: At the awake state, Eloc and Cp in the global topological attributes of hemi-brain network were 0.259±0.007 and 0.197±0.010, respectively, and decreased to 0.242±0.013 and 0.177±0.021, respectively after anesthesia, with statistically significant differences (all P<0.01). The topological attributes of the nodes in hemi-side brain showed that ND, NE and BC were increased in the default mode network-related brain regions, while NE and BC were decreased in the limbic system and subcortical structures. Eloc and Cp were 0.258±0.008 and 0.198±0.008 respectively in the patients with left hemisphere space occupying, and decreased to 0.241±0.011 and 0.177±0.015 respectively after anesthesia, with statistically significant differences (all P<0.01). However, only Eloc decreased in patients with right hemisphere space occupying after anesthesia, and Eloc was 0.260±0.006 and 0.243±0.016 respectively when awake and after anesthesia, with statistically significant differences (P<0.05). The topological attributes of nodes in patients with space occupying in different cerebral hemispheres showed bidirectional changes after anesthesia, and patients with space occupying in the left cerebral hemisphere were more likely to be widely affected after anesthesia. The effects of anesthetic drugs may show hemispheric laterality. If the tumor was in the dominant hemisphere, the compensatory function of the dominant side was more likely to be damaged. Conclusions: During anesthesia-induced loss of consciousness in patients with brain tumors, both the ability to integrate information and the functional connections between local regions are weakened, and some brain regions have functional connection reorganization. The changes of brain network after anesthesia are bidirectional regulation.

[Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) ß-thalassemia mutation with α-thalassemia and review of the literature].

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) ß-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and ß-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (ß-88 C>G/ßN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

[Clinical and pathological features of 20 cases of congenital hepatic fibrosis].

Objective: To investigate the clinical and pathological features of congenital hepatic fibrosis (CHF). Methods: The clinical and pathological findings of 20 patients diagnosed with CHF from 2017 to 2023 were retrospectively analyzed. Results: Among the 20 patients, 8 were males and 12 were females with a median age of 21.5 years. Mostly patients were admitted to the hospital with cirrhosis, portal hypertension and upper gastrointestinal bleeding. Pathological features were diffuse fibrosis in the portal area, formation of fibrous septa of varying width, segmentation of the liver parenchyma, with hyperplasia of small bile ducts. Among them, 1 case (5%) was complicated with Caroli's disease, and 1 case (5%) was HNF1α hepatocellular adenoma. IHC GS showed that was positively expressed in acinar region 3 in 75% cases. Conclusion: CHF is mainly manifested by portal hypertension and its complications. Histopathology is the gold standard for diagnosis. The possibility of CHF should be considered first in children and adolescents with portal hypertension but no history of hepatitis, and complicated kidney disease. The positive pattern of acinus-3 region of GS in IHC is helpful for the diagnosis of CHF.

[Analysis of strong invasive clinical features and poor prognosis in macrotrabecular-massive hepatocellular carcinoma].

Objective: To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis. Methods: The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS. Results: Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05). Conclusion: Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.

[Effect of sugammadex on postoperative nausea and vomiting after surgery for intracranial aneurysm].

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),>0.5-2.0 hours(T2),>2.0-6.0 hours (T3),>6.0-12.0 hours (T4) and >12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ2 or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ2=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). The results regarding the occurrence of complications in patients with different levels of PONV at different time intervals after surgery in the two groups were as follows: in the T3 time period of group N, a significant difference was observed only in the occurrence of postoperative complications among patients with different levels of PONV (χ2=24.786, P<0.01). However, in the T4 time period, significant differences were found in the occurrence of postoperative complications among both the same level and different level PONV patients (χ2=15.435, 15.435, both P<0.01). Significant differences were also observed in the occurrence of postoperative complications among the same level and different level PONV patients in both the T3 and T4 time periods of group S (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.

[Analysis of 14 cases of melanosis caused by 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene].

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.

Diagnostic accuracy of transvaginal ultrasound for detection of endometriosis using International Deep Endometriosis Analysis (IDEA) approach: prospective international pilot study.

OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in predicting deep endometriosis (DE) following the International Deep Endometriosis Analysis (IDEA) consensus methodology. METHODS: This was an international multicenter prospective diagnostic accuracy study involving eight centers across six countries (August 2018-November 2019). Consecutive participants with endometriosis suspected based on clinical symptoms or historical diagnosis of endometriosis were included. The index test was TVS performed preoperatively in accordance with the IDEA consensus statement. At each center, the index test was interpreted by a single sonologist. Reference standards were: (1) direct visualization of endometriosis at laparoscopy, as determined by a non-blinded surgeon with expertise in endometriosis surgery; and (2) histological assessment of biopsied/excised tissue. Surgery was performed within 12 months following the index TVS. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-) of TVS in the diagnosis of DE were calculated. RESULTS: Included in the study were 273 participants with complete clinical, TVS, laparoscopic and histological data. Of these, based on histology, 256 (93.8%) were confirmed to have endometriosis, including superficial endometriosis, and 190 (69.6%) were confirmed to have DE. Based on surgical visualization, 207/273 (75.8%) patients had DE. For DE overall, the diagnostic performance of TVS based on surgical visualization as the reference standard was as follows: accuracy, 86.1%; sensitivity, 88.4%; specificity, 78.8%; PPV, 92.9%; NPV, 68.4%; LR+, 4.17; LR-, 0.15, and the diagnostic performance of TVS based on histology as the reference standard was as follows: accuracy, 85.9%; sensitivity, 89.8%; specificity, 75.9%; PPV, 90.4%; NPV, 74.6%; LR+, 3.72; LR-, 0.13. CONCLUSIONS: Using the IDEA consensus methodology provides strong diagnostic accuracy for TVS assessment of DE. We found a higher TVS detection rate of DE overall than that reported by the most recent meta-analysis on the topic (sensitivity, 79%), albeit with a lower specificity. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Giant cell arteritis with stroke and systemic diffuse vasculitis.

Giant cell arteritis (GCA) is a systemic vasculitis, which mainly affects the aorta and its branches, while the abdominal aorta, the iliac artery and the limbs involvement are rare. The common clinical manifestations include headache, fever, jaw claudication, and visual impairment. Cerebrovascular accidents are relatively rare. Here, we present a GCA patient with stroke and systemic diffuse vasculitis involving the abdominal aorta, iliac artery, and femoral artery simultaneously.

[Impact of regional positive lymph node ratio of gallbladder carcinoma on prognosis].

Objective: To study the impact of regional positive lymph node ratio (LNR) on prognosis of patients with gallbladder carcinoma. Methods: The clinicopathological and survival data of 53 patients with gallbladder carcinoma who underwent radical resection with regional lymph node metastasis in Ningbo University Affiliated Lihuili Hospital from May 2012 to December 2020 were collected, and receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value of LNR for predicting postoperative survival status in patients with gallbladder carcinoma. According to the critical value, the patients were divided into low LNR group and high LNR group. The clinicopathological features and prognosis of the two groups were compared. Log rank test was used for univariate analysis of prognostic factors in patients with gallbladder carcinoma, and Cox proportional hazards model was used for multivariate analysis. Results: A total of 417 regional lymph nodes were dissected in 53 patients, of which 144 lymph nodes were positive, with a positive rate of 34.5%. The optimal cut-off value of LNR for predicting postoperative survival status of patients with gallbladder carcinoma was 0.33. According to this cut-off value, patients were divided into low LNR group (LNR≤0.33, 28 cases) and high LNR group (LNR>0.33, 25 cases). The recurrence rates were 64.3% (18/28) and 88.0 % (22/25) in low LNR group and high LNR group, respectively. The median recurrence-free survival (RFS) was 8 and 7 months, respectively (P=0.032). In the low LNR group, the 1-, 3-, and 5-year survival rates were 56.2%, 38.4%, and 32.0%, respectively, and the median overall survival (OS) was 16 months. In the high LNR group, the 1-, 3-, and 5-year survival rates were 37.9%, 5.4%, and 0, respectively, and the median OS was 9 months. The postoperative survival rate of patients in the low LNR group was better than that in the high LNR group (P=0.008). Univariate analysis showed that LNR was even associated with RFS and OS in patients with gallbladder carcinoma (P<0.05). Multivariate analysis showed that LNR>0.33 was an independent risk factor for postoperative RFS (HR=1.977, 95% CI: 1.045-3.740), but not for OS (HR=1.561, 95% CI: 0.685-3.553). Conclusion: On the basis of clearing a sufficient number of regional lymph nodes, patients with gallbladder carcinoma with regional LNR>0.33 are more likely to relapse after operation, but the predictive value of LNR>0.33 OS is insufficient.

[Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia].

Objective: To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) versus CAG regimen combined with decitabine (DAC) in elderly patients with relapsed acute myeloid leukemia (AML). Methods: From January 2018 to August 2020, the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 31 males and 14 females. The median age was 66 (60-80) years old. Eighteen patients were administrated with VEN and AZA, while the other 27 were in CAG with DAC. The complete remission (CR) rate, partial remission (PR) rate, total remission rate (ORR), adverse events and overall survival (OS) were compared between the two groups. Results: At the end of the treatment, the ORR in VEN with AZA group was 77.8% (14/18); including 11 CR and 3 PR. In CAG with DAC group, the ORR was 37.0% (10/27); including 8 CR and 2 PR (P=0.007). Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk (P=0.013) or with DNA methylation mutations (P=0.007). Main adverse events in both groups were bone marrow suppression, infections, nausea and vomiting, anorexia and fatigue. Grade Ⅲ-Ⅳ cytopenia developed in lower incidence of VEN with AZA group, such as leukopenia (66.7% vs. 100%, P=0.002), anemia (50.0% vs. 92.6%, P=0.002), thrombocytopenia (72.2% vs. 96.3%, P=0.031) and neutropenia (61.1% vs. 92.6%, P=0.014). In addition, less grade Ⅲ-Ⅳ infections occurred in VEN with AZA group (66.7% vs. 33.3%, P=0.028), as well as grade Ⅲ-Ⅳ gastrointestinal events (40.7% vs. 11.1%, P=0.032), grade Ⅲ-Ⅳ fatigue (55.6% vs.11.1%, P=0.003) compared with CAG with DAC group. The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9% and 31.6% respectively (P=0.150). Conclusion: VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.

[Clinical application of complete laparoscopic gastrectomy with function preservation of cardia in gastric carcinoma].

To investigate the feasibility and safety of total laparoscopic cardia function preserving gastrectomy for gastric carcinoma. Clinical data of 10 patients undergoing total laparoscopic cardia function preserving gastrectomy for gastric carcinoma from November 2020 to December 2021 were retrospectively collected. There were 7 males and 3 females. The mean age was (66.1±12.9) years (ranged from 38 to 86 years). All of the 10 patients were successfully performed total laparoscopic cardia function preserving gastrectomy without conversion to laparotomy. The time of digestive tract reconstruction was (24.8±3.3) min (20-30 min), and the intraoperative blood loss was (35±24) ml(20-100 ml). The time of postoperative exhaust was (2.5±0.9) days(2-3 d), the time of postoperative liquid diet was (2.25±0.87) days(2-3 d), postoperative hospital stay was (9.5±2.1) days(6-13 d). No surgical complications such as bleeding, anastomotic fistula or anastomotic stenosis occurred. Postoperative pathology showed that the proximal and distal margins of resected specimens were negative. Patients were followed up for 2 to 15 months, respectively. No death or tumor recurrence and metastasis occurred during the follow-up period. There were no symptoms of reflux after operation. Compared with total gastrectomy and proximal gastrectomy, total laparoscopic cardia function preserving gastrectomy can theoretically reduce the incidence of reflux esophagitis. We used manual suture method for digestive tract reconstruction, which can reduce the application of 2-3 stapling studs and reduce the cost of surgical materials. Compared with subtotal gastrectomy, total laparoscopic cardia function preserving gastrectomy has the advantages of more thorough lymph node dissection, with little residual gastric tissue; therefore, the blood supply is relatively better. The incidence of reflux esophagitis of total laparoscopic cardia function preserving gastrectomy for gastric cancer may was lower than total gastrectomy.

[Efficacy of in-situ full-left/full-right split liver transplantation for adult recipients using the living donor liver transplantation technique:a single-center report of 25 cases].

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ2 test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.

[Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head].

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

CircRNA_103801 accelerates proliferation of osteosarcoma cells by sponging miR-338-3p and regulating HIF-1/Rap1/PI3K-Akt pathway.

This study aimed to investigate the roles of hsa_circRNA_103801 in the progression of osteosarcoma (OS) cells. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the expression level of circRNA_103801 in OS cells. Cell count kit-8 and Transwell migration and invasion assays were employed to detect the proliferation, migration, and invasion abilities of OS cells. The effects of circRNA_103801 on the apoptosis of OS cells were identified by flow cytometry. The binding relationship between circRNA_103801 and miR-338-3p was verified by bioinformatics analysis. MiR-338-3p level in OS cell lines was detected by RT-qPCR. Additionally, Western blotting was utilized to detect the expression levels of HIF-1, Rap1, PI3K, and Akt in OS cells. The results showed that the expression level of circRNA_103801 was significantly up-regulated in OS patients' tissues. Inhibiting the expression level of circRNA_103801 could attenuate the proliferation, migration, and invasion abilities of OS cells. In addition, the down-regulated expression level of circRNA_103801 could induce cell apoptosis. The results of the luciferase reporter assay suggested that circRNA_103801 could be combined with miR-338-3p, and the RT-qPCR revealed that the miR-338-3p level in OS cells after knockdown of circRNA_103801 was elevated compared with the control group. The results of Western blotting suggested that the expression levels of HIF-1, Rap1, PI3K, and Akt were elevated in OS cells. In conclusion, the circRNA_103801-miR-3388-3p-HIF-1/Rap1/PI3K-Akt pathway could be a therapeutic target of OS.

Gene mapping reveals the association between tyrosine protein kinase Abl1 and the silk yield of Bombyx mori.

The Z chromosome of the silkworm contains a major gene that influences silk yield. This major locus on chromosome Z accounts for 35.10% of the phenotypic variance. The location and identification of the gene have been a focus of silkworm genetics research. Unfortunately, identification of this gene has been difficult. We used extreme phenotype subpopulations and selected from a backcross population, BC1 M, which was obtained using the high-yield strain 872B and the low-yield strain IS-Dazao as parents, for mapping the gene on the chromosome Z. The candidate region was narrowed down to 134 kb at the tip of the chromosome. BmAbl1 in this region correlated with silk gland development by spatiotemporal expression analysis. This gene was differentially expressed in the posterior silk glands of the high- and low-yield strains. In BmAbl1, an insertion-deletion (indel) within the 10th exonic region and an SNP within the 6th intronic region were detected and shown to be associated with cocoon shell weight in 84 Bombyx mori strains with different yields. Nucleotide diversity analysis of BmAbl1 and its 50 kb flanking regions indicated that BmAbl1 has experienced strong artificial selection during silkworm domestication. This study is the first to identify the genes controlling silk yield in the major QTL of the Z chromosome using forward genetics.

Anti-biofilm potential of kefir-derived Lactobacillus paracasei L10 against Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a kind of biofilm-forming foodborne bacterium, presents formidable challenges to the effectiveness of antimicrobial agents. Increasingly, the safety of chemical antimicrobials has aroused the widespread attention of the public. The development of the novel nature antimicrobial agents has become critical for controlling biofilm-related pollution and infections. In this paper, we investigated the antibacterial activity of Lactobacillus paracasei L10, and evaluated the inhibition and eradication effects of the cell-free supernatant (CFS) of the strain on V. parahaemolyticus biofilms in detail. We found that the CFS exhibited marked antibacterial activity against all tested pathogenic bacteria. In co-cultural assay, L. paracasei L10 could notably reduce cell viability in both plankton and biofilm of V. parahaemolyticus and this antagonism effect in biofilm was greater than that in planktonic state. Meanwhile, the growth of V. parahaemolyticus was completely inhibited when 6% (v/v) of the CFS was added, and the supernatant also showed a concentration-dependent manner to inhibit and eradicate the biofilms of V. parahaemolyticus while decreased the metabolic activity of the biofilm in the same way. Moreover, the fluorescence microscopic and confocal laser scanning microscopy images confirmed the anti-biofilm activity of the CFS. This study elucidates that L. paracasei L10 displays a significant anti-biofilm effect on V. parahaemolyticus and the mechanism of its antagonism merits further study, which provides theoretical support for further development and application of L. paracasei L10 as anti-biofilm agents.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.