ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome elements in type 2 diabetes mellitus （T2DM） patients based on maximum body mass index （maxBMI） and explore their association with complication risks. MethodsA retrospective cross-sectional study was used to collect clinical data from hospitalized T2DM patients， extracting age， gender， smoking history， alcohol consumption history， duration of disease， HbA1c level， complications， and TCM syndromes， and extracting the syndrome elements of disease location and disease nature based on their TCM syndromes. MaxBMI was calculated by telephone survey of patients' self-reported maximum body weight； patients with maxBMI ≥24 kg/m² were classified into spleen-heat syndrome group， and those with maxBMI ＜24 kg/m² were classified into consumptive-heat syndrome group. The distribution of TCM syndrome types and syndrome elements of patients in the two groups were analysed. Then the propensity score matching method was used to balance the baseline characteristics between the two groups and compare the differences in the distribution of syndrome types and syndrome elements and the risk of macrovascular and microvascular complications between the two groups. ResultsAmong the 1178 T2DM patients， syndrome elements in spleen-heat patients （1034 cases） were primarily located in the spleen （351 cases， 33.95%）， liver （240 cases， 23.21%）， and stomach （139 cases， 13.44%）， while in consumptive-heat patients （144 cases）， they were concentrated in the spleen （57 cases， 39.58%）， liver （34 cases， 23.61%）， and kidneys （17 cases， 11.81%）； regarding syndrome elements of disease nature， spleen-heat patients were predominantly characterized by qi deficiency （481 cases， 46.52%）， phlegm （353 cases， 22.73%）， and dampness （241 cases， 23.31%）， whereas consumptive-heat patients showed more qi deficiency （84 cases， 58.33%） and yin deficiency （44 cases， 30.56%）. After propensity score matching， 132 cases were included in each group， and no statistically significant differences were observed in the distribution of syndrome elements of disease location between the two groups （P＞0.05）， but the phlegm element was significantly more prevalent in spleen-heat patients than in consumptive-heat patients （P = 0.006）. Regarding the risk of complications， spleen-heat patients had a significantly higher risk of developing macrovascular complications compared to consumptive-heat patients （OR=2.04， P=0.010）， while no significant differences were found between groups in the occurrence of microvascular complications （P＞0.05）. ConclusionThe spleen-heat T2DM patients show a more frequent syndrome element of disease nature of phlegm， and a higher risk of developing macrovascular complications compared to consumptive-heat patients.

Objective To investigate a suspected outbreak of carbapenem-resistant Klebsiella pneumoniae(CRKP)healthcare-associated bloodstream infection(HA-BSI),provide reference for effective control of CRKP in-fection.Methods The characteristics of CRKP infected patients and the risk factors for the event transmission in an adult hematology department of a teaching hospital in June 2022 were obtained by field epidemiological investigation.The specimens of environmental target strains were co-llected by blood nutrient agar inoculation,the removal status of environmental microorganisms and the effect of infection control after implementing control measures were com-pared.Results There were a total of 6 cases of CRKP HA-BSI,with an attacking rate of 1.29％(6/464),which was significantly higher than 0 during the same period in 2021,and difference was statistically significant(P=0.011).In environmental hygiene monitoring,the detection rate of CRKP was 2.27％(1/44),which was from the surface of bed curtain in the living unit of infected patients,homology analysis with CRKP detected from 2 patients revealed that the 16s RNA of 3 CRKP strains was completely identical,with a similarity of 100％.Seven house-keeping genes of 3 CRKP strains were all identical and belonged to the ST11 type.Comprehensive control measures were taken:appropriate closure of the ward,centralized isolation of patients,terminal disinfection of the ward,reg-ular health care workers and relative restriction of their activity areas.After the measures were taken,the qualified rate of microbial colony count in the ward increased compared to before taking the measures(2.27％vs 68.89％,P＜0.001),with a statistically significant difference,there were no more CRKP infected cases after the intervention,indicating that the control measures were effective.Conclusion This outbreak was caused by ST11 type of common CRKP in China,and laminar bed curtains are carriers of pathogen transmission.It is speculated that non-standard cleaning and disinfection,as well as inadequate implementation of hand hygiene are the main causes for transmis-sion.Adopting an appropriate strategy of closing the ward and concentrating patient isolation can quickly and effec-tively prevent the transmission of the event.

Objective:To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined.Methods:Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted.Results:The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.216). Conclusions:The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

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 To investigate the prognostic evaluation value of the HALP score composed of hemoglobin,albumin,lymphocytes and platelets before chemotherapy in the patients with diffuse large B-cell lymphoma(DLBCL).Methods The clinical data and laboratory indicators before chemotherapy in the pa-tients with DLBCL newly diagnosed in this hospital from January 2015 to October 2022 were retrospectively analyzed.The optimal cut-off value of HALP was calculated by X-tile software.The patients were grouped ac-cording to the optimal cutoff value,the Chi-square test was used to analyze the difference in the constituent ra-tio of clinical characteristics among different HALP score groups,the survival curves of the progression-free survival(PFS)time and overall survival(OS)time among the groups with different scores were drawn by u-sing the Kaplan-Meier method,the Cox univariate and multivariate analysis regression model was adopted to analyze the prognostic influencing factors in DLBCL patients,and the predictive ability of HALP score for PFS time and OS time in DLBCL patients was evaluated by using the receiver operating characteristic(ROC)curve.Results A total of 132 patients with DLBCL were included,the optimal cutoff value of HALP score was 21.23 points.There were 54 cases in the low HALP score group and 78 cases in the high HALP score group.The low HALP score group was correlated with the later clinical stage,higher IPI and NCCN-IPI scores,higher LDH level and lower overall response rate(ORR)(P＜0.05).Compared to the high HALP score group,the PFS time and OS time in the low HALP score group were shorter(P＜0.05).The Cox uni-variate and multivariate regression model analysis results indicated that the HALP score≤21.23 points was an independent risk factor affecting the PFS time(HR=1.811,P=0.031).The ROC curve results suggested that the combination of HALP score combined with IPI score or NCCN-IPI score had higher predictive value for PFS time and OS time in DLBCL patients compared to use IPI or NCCN-IPI alone.Conclusion The HALP score is correlated with the prognosis of DLBCL patients,and could early identify the high-risk DLBCL patients with poor prognosis.The HALP score,IPI score and NCCN-IPI score combined evaluation has higher predictive value.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and has serious implications for the health of mothers and their offspring. In recent years, studies have confirmed that air pollution is one of the main risk factors for diabetes, and there is increasing evidence that air pollution exposure is closely related to the occurrence of gestational diabetes. However, current studies on the association between air pollutant exposure and the incidence of gestational diabetes are inconsistent, and the window period of pollutant exposure is still unclear. Limited mechanistic studies suggest that airborne particulate matter and gaseous pollutants may affect GDM through multiple mechanisms, including inflammation, oxidative stress, disruption of adipokine secretion, and imbalance of intestinal flora. This review summarizes the relationship between air pollutant exposure and the incidence of GDM in recent years, as well as the possible molecular mechanism of the occurrence and development of GDM caused by air pollutants, in order to provide scientific basis for preventing pollutant exposure, reducing the risk of GDM, improving maternal and fetal outcomes and improving the quality of the birth population.
Pregnancy ; Female ; Humans ; Diabetes, Gestational/epidemiology* ; Air Pollution/analysis* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Risk Factors ; Maternal Exposure/adverse effects*

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Receptors, Androgen/genetics* ; Nitriles ; Apoptosis

Objective:To explore the feasibility of deep learning-based restoration of obscured thyroid ultrasound images.Methods:A total of 358 images of thyroid nodules were retropectively collected from January 2020 to October 2021 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and the images were randomly masked and restored using DeepFillv2. The difference in grey values between the images before and after restoration was compared, and 6 sonographers (2 chief physicians, 2 attending physicians, 2 residents) were invited to compare the rate of correctness of judgement and detection of image discrepancies. The ultrasound features of thyroid nodules (solid composition, microcalcifications, markedly hypoechoic, ill-defined or irregular margins, or extrathyroidal extensions, vertical orientation and comet-tail artifact) were extracted according to the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). The consistency of ultrasound features of thyroid nodules before and after restoration were compared.Results:The mean squared error of the images before and after restoration ranged from 0.274 to 0.522, and there were significant differences in the rate of correctness of judgement and detection of image discrepancies between physicians of different groups(all P<0.001). The overall accuracy rate was 51.95%, the overall detection rate was 1.79%, there were significant differences also within the chief physicians and resident groups (all P<0.001). The agreement rate of all ultrasound features of the nodules before and after image restoration was higher than 70%, over 90% agreement rate for features such as solid composition and comet-tail artifact. Conclusions:The algorithm can effectively repair obscured thyroid ultrasound images while preserving image features, which is expected to expand the deep learning image database, and promote the development of deep learning in the field of ultrasound images.

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.

Objective:To investigate the expression of HER2 and its relationship with clinicopathological features in patients with urothelial carcinoma.Methods:Urothelial carcinoma specimens collected from January 2019 to June 2022 were used. The expression of HER2, cytokeratin 20 and cytokeratin 5/6 was examined using immunohistochemistry. The HER2 expression was assessed according to the clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China. Cases with HER2 2+/3+ were classified as HER2 positive. The relationship between HER2 expression and clinicopathological and molecular features was analyzed.Results:Four hundred and twenty-nine urothelial carcinoma specimens were analyzed, including 166 cases of raclical resection and 263 cases of local tumor resection. The median patient-age was 69 years (range: 31-93 years). The male: female ratio was 2.9∶1.0. The positive rate of HER2 was 45.7%(196/429). The positive rate of HER2 in patients with local tumor resection was higher than that in patients with radical resection [51.7%(136/263) vs.36.1%(60/166), P<0.05]. In the upper urinary tract (renal pelvis/ureter) urothelial carcinomas, the positive rate of HER2 was 35.2% (37/105). In bladder urothelial carcinoma, the positive rate of HER2 was 49.1%(157/320), and higher than that in upper urinary tract urothelial carcinoma ( P<0.05). In high grade urothelial carcinoma, the positive rate of HER2 was 52.8%(168/318) and higher than that in low grade urothelial carcinomas (25.2%, 28/111, P<0.01). In 166 radical resection specimens, the positive rate of HER2 was not differentially distributed by tumor pT stage [Ta (26.1%, 6/23), T1 (41.7%, 20/48), T2 (40.0%, 10/25), T3 (28.1%, 16/57), T4 (8/13) ( P>0.05)]. In urothelial carcinomas with muscle invasion, the HER2 positive rate was 35.8%(34/95), while the rate in non-muscle-invasion urothelial carcinoma was 36.6%(26/71, P>0.05). CK20 and CK5/6 were used to refine the urothelial carcinoma molecular subtypes. The positive rate of HER2 was highest in CK20 +/CK5/6 -group (124/194, 63.9%), followed by CK20 +/CK5/6 +group (18/40, 45.0%), CK20 -/CK5/6 -group (14/41, 34.1%) and CK20 -/CK5/6 +group (25/131, 19.1%, P<0.01). The positive rate of HER2 in micropapillary urothelial carcinoma was highest (14/15), followed by urothelial carcinoma with glandular differentiation (11/14), conventional urothelial carcinoma (161/360, 44.7%) and urothelial carcinoma with squamous differentiation (6/35, 17.1%, P<0.01). In the cases with lymph node metastasis, the positive rate of HER2 was 45.5% (10/22) and higher than the cases without lymph node metastasis (31.0%, 13/42). But there was no statistically significant association between HER2 expression and lymph node metastasis ( P>0.05). Conclusions:Expression of HER2 in urothelial carcinoma is closely correlated with tumor location, grade, histologic subtypes, molecular subtypes and surgical approach, but not with pT stage, muscle invasiveness or lymph node metastasis.