Background::This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods::We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018.Results::There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression-free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion::Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

Objective:To investigate the expression characteristics of mucin 5B (MUC5B) protein and programmed cell death factor 4 (PDCD4) protein in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram model for prognosis prediction.Methods:Clinical data of 100 patients who underwent radical surgical resection and were diagnosed as ICC by postoperative pathology from September 2009 to September 2020 in the Third Affiliated Hospital of Wenzhou Medical University were retrospectively selected, including 46 males and 54 females, aged (56.9±12.2) years old. Immunohistochemistry was used to detect the expression of MUC5B and PDCD4 protein in 100 cases of ICC and corresponding adjacent tissues respectively, and the relationship between them and clinicopathological factors of ICC patients was analyzed. Univariate and multivariate Cox regression analysis were performed to analyze the influencing factors on postoperative prognosis of ICC patients. The nomogram model was constructed using rms package and performed internal verification.Results:The positive expression rate of MUC5B protein in ICC was 76.0% (76/100), which was higher than that in para-cancer tissues 27.0%(27/100), and the difference was statistically significant ( χ2=11.33, P=0.015). While the positive expression rate of PDCD4 protein in ICC was 21.0%(21/100), which was lower than that in normal tissues 73.0% (73/100), and the difference was statistically significant ( χ2=15.57, P=0.007). Multivariate Cox regression analysis showed that ICC patients with carbohydrate antigen 19-9>37 kU/L, tumor length>5 cm, tumor TNM stage Ⅱ/Ⅲ, tumor medium/low differentiation, MUC5B positive expression, and PDCD4 negative expression had a high risk of short survival after resection (all P<0.05). The nomogram model was constructed based on the above indicators, and the C-index was 0.801. The postoperative survival calibration curve showed that the high predictive survival fit of the nomogram model, and the area under the receiver operating characteristic curve was 0.862. Conclusions:Positive expression of MUC5B protein and negative expression of PDCD4 protein in ICC tissue suggest poor prognosis of ICC patients. The nomogram model constructed on the basis of MUC5B and PDCD4 protein is well distinguished and has ideal predictive efficacy.

Objective To investigate the mental health status and its influencing factors among elderly hypertensive patients from Rural Areas of Chuxiong and Honghe Prefecture in Yunnan.Methods Multi-stage random sampling method was adopted to select elderly hypertensive patients from rural Yi ethnic areas in Yunnan.Questionnaires were used to collect their basic information and mental health status.Multivariate logistic regression was performed to explore the influencing factors of mental health among the elderly hypertensives.Results 21.82%(209/958)of elderly people with hypertension have poor mental health status in Chuxiong and Honghe Prefecture,Yunnan.Age of 80-89 years(OR = 2.395,P<0.05)and over 90 years(OR = 3.293,P<0.05),as well as physical disability(OR = 2.037,P<0.05),were risk factors for poor mental health.Compared with those who rated their economic situation as very difficult,rating as somewhat difficult(OR = 0.490,P<0.05),moderate(OR = 0.632,P<0.05)and relatively affluent(OR = 0.344,P<0.05),having a spouse(OR = 0.655,P<0.05),received full concern from the offspring(OR = 0.411,P<0.05)and maintain good relationships with offspring(OR = 0.339,P<0.05)were protective factors.Conclusions The mental health status of elderly people with hypertension is relatively poor in rural areas of Chuxiong and Honghe Prefecture in Yunnan Province.Special attention should be paid to the mental health of older and physically disabled elderly hypertensives.Economic and mental support from children was crucially important in improving the mental health of elderly hypertensive patients in rural areas of Chuxiong and Honghe Prefecture in Yunnan Province.

Background::This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods::We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018.Results::There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression-free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion::Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

OBJECTIVES: To investigate the effects and mechanisms of deubiquitinating enzyme Josephin domain containing 2 (JOSD2) on susceptibility of non-small cell lung carcinoma (NSCLC) cells to anti-cancer drugs. METHODS: The transcriptome expression and clinical data of NSCLC were downloaded from the Gene Expression Omnibus. Principal component analysis and limma analysis were used to investigate the deubiquitinating enzymes up-regulated in NSCLC tissues. Kaplan-Meier analysis was used to investigate the relationship between the expression of deubiquitinating enzymes and overall survival of NSCLC patients. Gene ontology enrichment and gene set enrichment analysis (GSEA) were used to analyze the activation of signaling pathways in NSCLC patients with high expression of JOSD2. Gene set variation analysis and Pearson correlation were used to investigate the correlation between JOSD2 expression levels and DNA damage response (DDR) pathway. Western blotting was performed to examine the expression levels of JOSD2 and proteins associated with the DDR pathway. Immunofluorescence was used to detect the localization of JOSD2. Sulforhodamine B staining was used to examine the sensitivity of JOSD2-knock-down NSCLC cells to DNA damaging drugs. RESULTS: Compared with adjacent tissues, the expression level of JOSD2 was significantly up-regulated in NSCLC tissues (P<0.05), and was significantly correlated with the prognosis in NSCLC patients (P<0.05). Compared with the tissues with low expression of JOSD2, the DDR-related pathways were significantly upregulated in NSCLC tissues with high expression of JOSD2 (all P<0.05). In addition, the expression of JOSD2 was positively correlated with the activation of DDR-related pathways (all P<0.01). Compared with the control group, overexpression of JOSD2 significantly promoted the DDR in NSCLC cells. In addition, DNA damaging agents significantly increase the nuclear localization of JOSD2, whereas depletion of JOSD2 significantly enhanced the sensitivity of NSCLC cells to DNA damaging agents (all P<0.05). CONCLUSIONS Deubiquitinating enzyme JOSD2 may regulate the malignant progression of NSCLC by promoting DNA damage repair pathway, and depletion of JOSD2 significantly enhances the sensitivity of NSCLC cells to DNA damaging agents.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Antineoplastic Agents/pharmacology* ; Lung Neoplasms/genetics* ; DNA Damage ; DNA ; Deubiquitinating Enzymes/genetics*

OBJECTIVE: To investigate the clinical significance of early troponin I (TnI) level in the prognosis of severe heat stroke. METHODS: Clinical data of 131 patients with severe heat stroke in the intensive care unit (ICU) of the Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University (study dataset) and ICU 67 patients with severe heat stroke in Jintan First People's Hospital of Changzhou (validation dataset) were retrospectively analyzed from June 2013 to September 2022. The patients were divided into survival group and death group according to 30-day outcomes. TnI was collected within 24 hours after admission to the emergency department. Cox regression analysis was performed to analyze the risk factors of severe heat stroke death. Spearman correlation test was used to analyze the correlation between TnI and heart rate, and peripheral systolic blood pressure. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of TnI for death in patients with severe heat stroke. Decision curve analysis (DCA) was conducted to assess the clinical net benefit rate of TnI prediction. Grouping by TnI cut-off value, Kaplan-Meier survival curve was used to analyze 30-day cumulative survival. Sensitivity analysis included modified Possion regression, E-value, and subgroup forest map was used to evaluate the mortality risk of TnI in different populations. External dataset was used to verify the predictive value of TnI. RESULTS: The death group had significantly higher TnI compared to the survival group [μg/L: 0.623 (0.196, 1.510) vs. 0.084 (0.019, 0.285), P < 0.01]. Multivariate Cox regression analysis after adjusting for confounding factors showed that TnI was an independent risk factor for death [hazard ratio (HR) = 1.885, 95% confidence interval (95%CI) was 1.528-2.325,P < 0.001]. Spearman correlation test showed that TnI was positively correlated with heart rate (r = 0.537, P < 0.001) and negatively correlated with peripheral systolic blood pressure (r = -0.611, P < 0.001). ROC curve showed that the area under the curve (AUC) of the TnI (0.817) was better than that of the acute physiology and chronic health evaluation II (APACHE II, 0.756). The DCA curve showed that the range of clinical net benefit rate of TnI (6.21%-20.00%) was higher than that of APACHE II score (5.14%-20.00%). Kaplan-Meier survival curve showed that patients in the low-risk group (TnI ≤ 0.106) had a significantly higher 30-day survival rate than that in the high-risk group (TnI > 0.106) group (Log-Rank test: χ² = 17.350, P < 0.001). Modified Possion regression with adjustment for confounding factors showed that TnI was still an independent risk factor for death in patients with severe heat stroke [relative risk (RR) = 1.425, 95%CI was 1.284-1.583, P < 0.001]. The E-value was 2.215. The subgroup forest plot showed that the risk factors of TnI were obvious in male patients and patients ≤ 60 years old (male: HR = 1.731, 95%CI was 1.402-2.138, P < 0.001; ≤ 60 years old: HR = 1.651, 95%CI was 1.362-2.012, P < 0.001). In the validation dataset, ROC curve analysis showed that the AUC (0.836) of TnI predicting the prognosis of severe heat stroke was still higher than the APACHE II score (0.763). CONCLUSIONS Early elevation of TnI is a high-risk factor for death in patients with severe heat stroke, and it has a good predictive value for death.
Humans ; Male ; Middle Aged ; Troponin I ; Retrospective Studies ; Clinical Relevance ; ROC Curve ; Prognosis ; Intensive Care Units ; Heat Stroke/diagnosis* ; Sepsis

Objective:To evaluate the effects of hemoclips on preventing delayed bleeding for early gastric cancer (EGC) after endoscopic submucosal dissection (ESD).Methods:Clinical data of 459 patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to August 2020 were collected retrospectively. Patients were divided into group A (hemoclip group, n=162) and group B (non-hemoclip group, n=297) according to whether preventive hemostatic clip treatment was performed after resection. Delayed bleeding within 2 weeks after ESD was observed. Univariate analysis and subgroup analysis were conducted for the delayed bleeding incidence and clinicopathological features. Results:Delayed bleeding incidences of group A and group B were 3.1% (5/162) and 8.1% (24/297) with significant difference between the two groups ( χ2=4.418, P=0.036). Subgroup analysis showed that there were significant differences in the delayed bleeding incidence between the two groups when the diameter of the tumor >20 mm [3.5% (2/57) VS 15.3% (13/85), χ2=5.016, P=0.025], the tumor located in the lower part of the stomach [1.0% (1/97) VS 10.4% (20/192), χ2=8.425, P=0.004], and the depth of tumor invasion was M/SM1 [3.2% (5/157) VS 8.1% (23/285), χ2=4.072, P=0.044]. There were no significant differences in the delayed bleeding incidence between group A and group B when the diameter of the tumor ≤20 mm, the tumor located in the upper/medial part of the stomach and the depth of tumor invasion was SM2 ( P>0.05). Conclusion:Hemoclips can prevent delayed bleeding after ESD for EGC, which is mainly observed in a tumor of diameter >20 mm, located in the lower part of the stomach and M/SM1 tumor invasion. It has little effect on the prevention when the tumor diameter ≤20 mm and located in the upper/medial part of the stomach.

Objective:To analyze the clinicopathological features of de novo early colorectal cancer and to evaluate the efficacy of endoscopic treatment.Methods:Patients with de novo early colorectal cancer who underwent endoscopic resection in Beijing Friendship Hospital, Capital Medical University from June 2020 to May 2022 were enrolled. The baseline data, endoscopic manifestations, treatment methods, postoperative pathological results and prognosis of the patients were collected retrospectively.Results:A total of 33 patients with de novo early colorectal cancer were enrolled with the age of 62.67 ± 8.62 years, and the male to female ratio was 7.25∶1. The long diameter of lesions was 0.96 ± 0.36 cm. The lesion morphology was mainly superficial phenotype (type 0-Ⅱ), accounting for 72.7% (24/33). Endoscopic submucosal dissection (ESD) was performed in 29 cases and endoscopic mucosal resection (EMR) was performed in 4 cases. Postoperative pathology showed that 11 cases (33.3%) were well differentiated tubular adenocarcinoma, of which the superficial submucosal layer was invaded in 2 cases. Twenty cases (60.6%) were moderately differentiated tubular adenocarcinoma, of which the superficial submucosa layer was invaded in 5 cases and the deep submucosa layer in 15 cases. Two cases (6.1%) were moderately-poorly differentiated tubular adenocarcinoma, where the deep submucosa layer was invaded in both. There was significant correlation between the depth of invasion and the degree of differentiation ( P<0.001), and moderately and moderately-poorly differentiated lesions were more likely to invade the deep submucosa layer. The en bloc resection rate was 100.0% (33/33), the complete resection rate was 97.0% (32/33), and the curative resection rate was 42.4% (14/33). Among the 19 patients who did not achieve curative resection, 13 patients received supplementary surgical treatment. No tumor residue or lymph node metastasis was found in the postoperative pathology. All patients were followed up for 3-25 months, and no signs of local recurrence or metastasis were found. Conclusion:Most de novo early colorectal cancers are superficial phenotype under endoscopy. The pathology is mainly moderately differentiated tubular adenocarcinoma. Endoscopic resection of de novo early colorectal cancer shows encouraging short-term efficacy.

Objective:To explore the practice of comprehensive teaching based on multiple evaluation in general surgery practice teaching.Methods:A total of 83 students were selected from the General Surgery Department, The Second Affiliated Hospital of Harbin Medical University. Among them, 40 interns used traditional teaching (control group) and 43 interns used comprehensive teaching based on multiple evaluation (experimental group). After the teaching, the assessment results of the theoretical knowledge and skill operation of the two groups of interns were evaluated, and the instructor evaluated the comprehensive ability of the interns, and evaluated the teaching satisfaction and teaching feedback results. SPSS 24.0 was used for t-test and Chi-square test. Results:After the teaching, the examination scores of interns' theoretical knowledge and skill operation in the experimental group [(94.24±2.28) points and (92.33±2.58) points] were higher than those in the control group [(90.56±2.37) points and (88.75±2.41) points]. The scores of independent learning ability, independent thinking ability, logical thinking ability, group cooperation ability, and humanistic care ability of interns in the two groups after teaching were significantly higher than those before teaching, and the scores of each ability in the experimental group were higher than those in the control group ( P<0.05). The total satisfaction rate of interns in the experimental group [95.35% (41/43)] was higher than that in the control group [75.00% (30/40)], and the difference was statistically significant ( P<0.05). The experimental group in improving the participation and learning efficiency of interns in teaching activities [97.67% (42/43), 90.70% (39/43)] was significantly higher than the control group [75.00% (30/40), 70.00% (28/40)] ( P<0.05). Conclusion:The application of comprehensive teaching based on multiple evaluation in general surgery practice teaching can help improve the interns' theoretical knowledge and skill operation performance, improve their comprehensive ability and teaching satisfaction, and improve their learning enthusiasm and efficiency, which deserves promotion and application.

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital’s electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%).Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.