OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

Objective Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection.Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes.Recently,it has been reported that the T cell immunoglobulin and mucin domain protein 3(Tim-3)and its ligand galactose lectin 9(galectin-9)play crucial roles in immune dysfunction caused by various tumors,such as colorectal cancer.However,their expressions,biological functions,and prognostic value in colorectal cancer are still unclear.This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer.Methods A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected.Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients.The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly.Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival(RFS)and the overall survival(OS)of colorectal cancer patients.Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients.Results The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18%(120/171)and 32.16%(55/171),respectively,of the colorectal cancer tissues,whereas the low expression levels were 29.82%(51/171)and 67.84%(116/171),respectively.Furthermore,the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues,while the expression score of galectin-9 was lower than that in the paracancerous tissues(P＜0.05).Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration,vascular infiltration,and clinical staging(P＜0.05).During the follow-up period of 14-63 months,7 out of 171 patients were lost to follow-up.Among the remaining patients,49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9,respectively,whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9,respectively.Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did(RFS:log-rank=22.66,P＜0.001;OS:log-rank=19.71,P＜0.001).Conversely,patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did(RFS:log-rank=19.45,P＜0.001;OS:log-rank=22.24,P＜0.001).Cox multivariate analysis indicated that TNM stage Ⅲ(HR=2.26,95%CI:1.20-5.68),high expression of Tim-3(HR=0.80,95%CI:0.33-0.91),and low expression of galectin-9(HR=1.80,95%CI:1.33-4.70)were independent risk factors affecting RFS and OS in patients(P＜0.05).Conclusion Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues.High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis.They are identified as independent influencing factors that may trigger adverse prognostic events in patients.These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.
Humans ; Prospective Studies ; Antifungal Agents ; Glucocorticoids ; Rapid On-site Evaluation ; Reproducibility of Results ; Pulmonary Aspergillosis ; Pneumonia ; Diabetes Mellitus ; Adenocarcinoma of Lung ; Vasculitis ; Retrospective Studies

Objective:To investigate the influencing factors of endotracheal intubation and mechanical ventilation (ETI-MV) in patients with acute respiratory distress syndrome (ARDS) caused by viral pneumonia, and to provide evidence for individualized use of ETI-MV.Methods:Patients with ARDS due to viral pneumonia admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed from November 2017 to March 2022. The gender, age, concomitant diseases, clinical symptoms and signs, complications, lab results, ARDS severity, infectious virus type, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), respiratory support methods and prognosis-related variables were collected. Univariate analysis was performed on each factor, and the variables with statistical significance in the univariate analysis were subjected multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each index for the implementation of ETI-MV.Results:A total of 117 patients were enrolled in the study, including 61 patients in the ETI-MV group, and 3 patients (4.9%), 39 patients (63.9%) and 19 patients (31.1%) with mild, moderate and severe ARDS, respectively. There were 56 patients in non-ETI-MV group, and the mild, moderate and severe ARDS cases were 16 cases (28.6%), 38 cases (67.8%) and 2 cases (3.6%), respectively. There was significant difference between the two groups ( P < 0.05). Univariate analysis showed that during 24 hours admitted to RICU, the levels of interleukin-6 [IL-6 (ng/L): 104.0±90.0 vs. 62.4±76.0], oxygenation index [PaO 2/FiO 2 (mmHg, 1 mmHg≈0.133 kPa): 123.9±30.9 vs. 173.6±28.5], the proportion of cases with pulmonary infiltrating opacity distribution range ≥ 3/4 lung fields [85.3% (52/61) vs. 21.5% (12/56)], APACHE Ⅱ score ≥ 16.5 [67.2% (41/61) vs. 42.9% (24/56)], the rate of nosocomial invasive aspergillus infection [14.8% (9/61) vs. 3.6% (2/56)], the percentage of nosocomial bacterial infection [16.4% (10/61) vs. 3.6% (2/56)], and the lowest CD4 + T lymphocyte count in the course of the disease [cells/mm 3: 192.2±35.8 vs. 215.0±58.3] had significant differences between ETI-MV and non-ETI-MV group (all P < 0.05). Multivariate Logistic regression analysis showed that during 24 hours admitted to RICU the distribution range of pulmonary infiltrating opacity ≥ 3/4 the lung fields [odds ratio ( OR) = 12.527, 95% confidence interval (95% CI) = 3.279-47.859, P < 0.001], APACHE Ⅱ score ≥ 16.5 ( OR = 30.604, 95% CI = 4.318-216.932, P = 0.001), PaO 2/FiO 2 ( OR = 0.948, 95% CI = 0.925-0.972, P < 0.001), CD4 + T lymphocytes cell count ( OR = 0.975, 95% CI = 0.955-0.995, P = 0.015), and nosocomial bacterial infection ( OR = 38.338, 95% CI = 1.638-897.158, P = 0.023) were independent risk factors for ETI-MV. The area under the ROC curve (AUC) of ROC showed that PaO 2/FiO 2 had the greatest predictive value for ETI-MV, with AUC of 0.903, sensitivity of 91.1% and specificity of 95.1% in case of cutoff value of 151 mmHg. The AUC of pulmonary infiltrating opacity distribution range was 0.809, the sensitivity of 85.2%, specificity of 78.6% when the cutoff value was ≥ 3/4 lung field. APACHE Ⅱ scores had the lowest predictive value for selecting ETI-MV, with AUC of 0.704, sensitivity of 83.6% and specificity of 57.1% under the cutoff value was 16.5. Conclusions:For patients with ARDS caused by viral pneumonia, PaO 2/FiO 2 is still the classic reference for selecting ETI-MV, however, the distribution range of pulmonary infiltrating opacity and the systemic severity of the disease during 24 hours admitted to the RICU may provide supplemental helpful information to determine whether the patients choose ETI-MV, especially for moderate ARDS.

Objective:To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) .Methods:Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed.Results:The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up.Conclusion:A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

Objective:To investigate the expression of fibroblast growth factor 7 (FGF7) and related inflammatory factors in the serum of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods:A case control study was conducted. The patients with AECOPD admitted to the First Affiliated Hospital of Xinjiang Medical University from November 2016 to January 2020 were enrolled. The patients were divided into mild group [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio (FEV1/FVC) < 0.70, FEV1 percentage in predicted value (FEV1%) ≥ 80%], moderate group (FEV1/FVC < 0.70, 50% ≤ FEV1% < 80%), and severe group (FEV1/FVC < 0.70, 30% ≤ FEV1% < 50%) based on their lung function test results, with 20 patients in each group, and 20 patients with normal pulmonary function who underwent elective non-thoracic surgery such as gastrointestinal surgery and orthopedics surgery in the same period were selected as controls. The demographic data, FEV1/FVC, FEV1%, FVC, maximum mid-expiratory flow percentage in predicted value (MMEF%), 6-minute walking test (6MWT), and St George Respiratory Questionnaire (SGRQ) score were recorded respectively. Serum levels of FGF7, interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Pearson correlation was used to analyze the correlation between TNF-α and lung function.Results:Compared with the normal pulmonary function group, the levels of FEV1/FVC, FEV1%, MMEF% and 6MWT in the mild, moderate and severe groups were significantly decreased, and the SGRQ scores were increased, the indicators continued to deteriorate with the aggravation of the disease, the statistical differences were found between severe group and normal pulmonary function group [FEV1/FVC: 0.39±0.09 vs. 0.81±0.04, FEV1%: (38.80±6.28)% vs. (109.58±13.80)%, MMEF%: (0.34±0.14)% vs. (2.69±0.99)%, 6MWT (m): 279.00±41.61 vs. 402.85±53.97, SGRQ scores: 34.95±6.71 vs. 2.60±2.06, all P < 0.05]. Compared with the normal pulmonary function group, the levels of FGF7 in the mild, moderate and severe groups were significantly lowered (ng/L: 6.31±2.65, 6.10±1.39, 6.64±1.77 vs. 8.29±3.51, all P < 0.05), but no significant difference was found among the mild, moderate and severe groups (all P > 0.05). Compared with the normal pulmonary function group, IL-6 and TNF-α levels were significantly increased in the mild, moderate and severe groups, and TNF-α increased with the aggravation of the disease, the statistical difference was found between severe group and normal pulmonary function group (ng/L: 7.42±2.28 vs. 3.83±0.92, P < 0.05). There was no significant difference in IL-1β level between the normal pulmonary function group and the mild, moderate, severe groups. Correlation analysis showed that TNF-α was negatively correlated with FEV1/FVC and FEV1% ( r values were -0.350 and -0.527, respectively, both P < 0.01). Conclusion:In AECOPD patients, serum FGF7 was decreased, while IL-6 and TNF-α were increased; however, with the aggravation of the disease, there was no significant change in the level of FGF7 in the peripheral blood, but the TNF-α level might be increased, accompanied by severe damage of small airway function.

Objective:To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme.Methods:Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH 2O (1 cmH 2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH 2O and the ratio of inspiratory to expiratory time 1.5-2.5∶1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH 2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. Results:Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). Conclusion:For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

Objective To investigate the correlation of interleukin-1β (IL-1β) ,homocysteine (HCY) ,cysta-tin (Cys-C) and glycosylated hemoglobin (HbA1c) levels and senile type 2 diabetic peripheral neuropathy. Methods 104 patients with type 2 diabetes mellitus received in the hospital from June 2014 to December 2016 were selected as study group ,52 patients with peripheral neuropathy were served as study group A (n=52) and 52 patients with type 2 diabetes were served as study group B (n=52) ,and 52 healthy persons who under-went health assessement were taken as the control group.The Cys-C level was measured by immunoturbidime-try ,the levels of HCY and IL-1β were measured by enzyme-linked immunosorbent assay.The HbA1c level was measured by high performance liquid chromatography ,the IL-1β ,HCY ,Cys-C and HbA1c levels were com-pared in the three groups ,and the relationship between IL-1β ,HCY ,Cys-C and HbA1c levels and senile type 2 diabetic peripheral neuropathy were analyzed.Results Single factor variance analysis showed that the levels of IL-1β ,HCY ,Cys-C and HbA1c in the three groups were statistically significant (P＜0.05) ;LSD-t test showed that the IL-1β ,HCY ,Cys-C and HbA1c levels in the study group B were higher than those in control group , and IL-1β ,HCY ,Cys-C and HbA1c levels in the study group A were higher than those in the study group B , and the difference was statistically significant (P＜ 0.05) ;logisticis regression analysis showed that IL-1β , HCY ,Cys-C ,HbA1c levels were associated with type 2 diabetic peripheral neuropathy (P＜0.05) ;Spearman test showed that IL-1β ,HCY ,Cys-C ,HbA1c levels were positively correlated with type 2 diabetic peripheral neuropathy (P＜0.05).Conclusion IL-1β ,HCY ,Cys-C and HbA1c levels are positively correlated with senile type 2 diabetic peripheral neuropathy in the elderly ,and the IL-1β ,HCY ,Cys-C and HbA1c levels can be used to determine type 2 diabetic peripheral neuropathy in clinical work.

Objective To explore the association between the genetic polymorphism of CYP3A4,CYP2D6 and response to methadone maintenance treatment(MMT)among heroin-dependent patients.Methods Patients undergoing MMT in 6 MMT clinics were randomly selected,information about general socia-demographic characteristics,drug abuse history,and MMT data of patients were collected,genotypes of peripheral blood CYP3A4 and CYP2D6 polymorphic loci were detected.Results A total of 820 patients were enrolled in the study,210 cases were with good response and 610 cases with poor response to MMT.Difference in age between different response groups was statistically significant(P<0.05).Distribution of genotype frequency and allele frequency of CYP3A4 rs2242480 and CYP2D6 rs16947 between good response and poor response groups was not significantly different(both P>0.05).Conclusion The association between CYP3A4 rs2242480,CYP2D6 rs16947 and response to MMT has not yet found in heroin-dependent patients.

Objective To study the distributions of three single nucleotide polymorphisms (SNPs) in β-arrestin2 (ARRB2) which including rs3786047,rs1045280 and rs2036657 and to elucidate the relationship between these SNPs and response to methadone maintenance treatment (MMT) among heroin-dependent patients of Han ethnicity population in Hunan.Methods Han MMT patients were recruited in four random-chosen MMT clinics from Hunan province.Demographics,history of drug-use and MMT were recorded.ARRB2 SNPs were genotyped to determine the association between SNPs and response to MMT.Results Distributions of the three SNPs were in Hardy-Weinberg equilibrium in both groups (responders vs.non-responders).There was no statistical significance in the distribution frequency of genotype on rs3786047 (x2=0.486 2,P=0.784),rs1045280 (x2=1.591 9,P=0.451) and rs2036657 (x2=1.061 5,P=0.588) in ARRB2 among the responders or the non-responders.Conclusion Associations between the ARRB2 genotypes,rs3786047,rs1045280 and rs2036657,and MMT response in Han MMT patients in Hunan province did not appear.