Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To explore the impacts of thermotherapy combined with gemcitabine on the biological behavior of tongue squamous cell carcinoma cells.Methods:Human tongue squamous cell carcinoma Tca8113 cells were divided into the control group (blank control), gemcitabine group, thermotherapy group (heated in an incubator at 43℃ for 1 h and then incubated at 37℃ for 24 h) and thermotherapy + gemcitabine group. The proliferation ability of Tca8113 cells was assessed by EdU staining and CCK-8 assay. Cell apoptosis and cell cycle of Tca8113 cells were detected by flow cytometry. The invasion of Tca8113 cells was determined by Transwell chamber assay. The expression levels of cyclin D1 (CyclinD1), Bcl-2-associated X protein (Bax), matrix metalloproteinase (MMP)-9, phosphorylated histone H2AX (γH2AX) and Nijmegen breakage syndrome 1 (NBS1) proteins in Tca8113 cells were measured by Western blot. The changes of tumor mass and volume were detected by xenograft tumor in vivo test in nude mice. Multi-group comparison was performed by one-way ANOVA. Two group comparison was conducted by SNK- q test. Results:Compared with the control group, EdU positive cell percentage, OD 450 value, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas the apoptosis rate, the expression of Bax and γH2AX proteins were increased in the gemcitabine, thermotherapy and thermotherapy + gemcitabine groups ( q=4.45-72.06, all P<0.001). Compared with the control group, the proportion of G 0/G 1 phase cells was decreased, whereas the proportion of S and G 2/M phase cells was increased in the gemcitabine and thermotherapy + gemcitabine groups, the proportion of G 0/G 1 phase cells was decreased and the proportion of G 2/M phase cells was increased in the hyperthermia group ( q=10.36-61.09, all P<0.001). Compared with the gemcitabine and thermotherapy groups, EdU positive cell percentage, OD 450 value, G 0/G 1 phase cell proportion, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas apoptosis rate, S, G 2/M phase cell proportion, Bax and γH2AX protein expression were increased in the thermotherapy + gemcitabine group ( q=4.45-28.73, all P<0.001). Xenograft tumor in vivo test in nude mice showed that the tumor volume and mass of nude mice in the gemcitabine, thermotherapy, and thermotherapy + gemcitabine groups were decreased compared with those in the control group ( q=5.58-73.02, all P<0.001). Compared with the gemcitabine and thermotherapy groups, the tumor volume and mass in the thermotherapy + gemcitabine group were decreased ( q=5.58-21.45, all P<0.001). Conclusion:The combination of thermotherapy and gemcitabine can inhibit the proliferation and invasion, block the cell cycle, and induce cell apoptosis of Tca8113 cells.

Objective:To investigate electrocardiogram (ECG) characteristics and related factors of gestational diabetes mellitus (GDM) complicated by depressive disorder.Methods:The clinical data of 243 patients with GDM who received treatment at Peking University Third Hospital from September 2021 to December 2022 were retrospectively analyzed. According to the scoring results of the Self-rating Depression Scale (SDS), these patients were divided into an observation group (GDM + depressive disorder, n = 51) and a control group (GDM alone, n = 192). The χ2 test was used to analyze the relationship between GDM complicated by depressive disorder and ECG diagnosis results. Additionally, the t-test was used to compare ECG indicators between the two groups. Results:Compared with the control group, patients in the observation group had a higher incidence of abnormal ECG indicators, including bradycardia ( χ2 = 4.68, P = 0.030), premature contraction ( χ2 = 10.78, P = 0.001), and atrioventricular block ( χ2 = 15.04, P < 0.001). However, there were no significant differences in the incidences of tachycardia, bundle branch block, or ST-T changes between the two groups (all P > 0.05). Compared with the control group, the observation group exhibited significantly increased heart rate [(73.43 ± 8.24) beats/min vs. (67.22 ± 5.08) beats/min], maximum QT interval [(419.09 ± 36.00) ms vs. (351.95 ± 32.07) ms], minimum QT interval [(363.31 ± 30.78) ms vs. (316.52 ± 29.10) ms], and QT dispersion [(55.78 ± 17.87) ms vs. (35.42 ± 13.18) ms, t = -5.13, -12.95, -10.08, -7.60, all P < 0.001]. Conclusion:Among patients with gestational diabetes mellitus, those with depressive disorder have an increased risk of exhibiting abnormal electrocardiogram patterns compared with those without depressive disorder.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Hyperthermia, as an adjunct to radiotherapy and chemotherapy, can change the immune condition of tumor microenvironment and enhance the effect of tumor treatment without damaging normal tissues. Tumor-associated macrophages are the main immune cells in the tumor microenvironment, and there are two subtypes: M1 phenotype can inhibit the growth of tumor cells, and M2 phenotype can promote the occurrence and metastasis of tumor cells. Therefore, repolarization of M2 phenotype into M1 phenotype is a new research direction. In this paper, the mechanisms of hyperthermia and tumor-associated macrophage repolarization were reviewed based on the current research progress at home and abroad, aiming to provide novel ideas for tumor therapy.

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.
Humans ; Male ; Antiviral Agents/therapeutic use* ; China ; Hepatitis C/drug therapy* ; Hepacivirus ; Logistic Models

Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Vascular endothelial growth factor (VEGF) plays an important role in promoting tumor vascular growth and changing vascular wall permeability. With the in-depth study of tumor hyperthermia and tumor microenvironment, more and more studies have shown that hyperthermia exerts multiple regulatory effects on VEGF in tumor microenvironment. Combined with current research progress in China and abroad, this article reviews the effect of hyperthermia on VEGF and its related cells and factors in tumor microenvironment, aiming to provide new ideas for the clinical application of tumor hyperthermia combined with immune or targeted therapy.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*