Responding to the Growing Need for Medical Experts in Testamentary and Estate Related Capacities: A Course for Physicians.

OBJECTIVES: The objective of this continuing medical education course was to improve the knowledge and skills of physicians in the assessment of testamentary and related capacities. METHODS: We developed, conducted, and evaluated an accredited medical education course focusing on the role and responsibilities of medical experts in estate litigation and held in Toronto, Ontario, Canada in June 2022. RESULTS: Participants reported a 65% and 35% improvement in confidence in conducting retrospective and contemporaneous assessments of testamentary capacity, respectively. The overall mean score in the 9 key competencies for medical experts in estate litigation improved by 1.2-points from 3.02 (SD 1.33) to 4.22 (SD 0.74) from pre to postcourse (p <0.05, 95% CI [-1.66, -0.67]). CONCLUSIONS: This course addresses a significant gap in training and formal education opportunities in testamentary and other related capacities that may contribute to increasing the pool of available and qualified medical experts in estate litigation.

Effects of Three Different Heating Devices on Patients Undergoing Surgery: A Network Meta-Analysis.

PURPOSE: Perioperative hypothermia is a common anesthesia-related complication that can result in negative outcomes. Intraoperative active heating can positively impact these outcomes. Therefore this study aimed to investigate the effectiveness of three common heating devices for controlling hypothermia, improving thermal comfort, and reducing anesthesia recovery time. DESIGN: Systematic review and meta-analysis. METHODS: Seven electronic literature databases were searched from the inception date of the databases to March 18, 2022. RevMan 5.4 and Stata 15.1 were used to perform meta-analyses on the obtained data, and the Cochrane Evaluation Manual was used for quality risk assessment of the included studies. FINDINGS: A total of 18 studies involving 1,511 patients undergoing surgery using heating devices were included. In this meta-analysis, a ranking method known as the Surface Under the Cumulative Ranking Curve (SUCRA) was used. SUCRA provides a numerical measure of the effectiveness of treatments, with higher values indicating superior efficacy. Findings demonstrated that the concurrent use of three heating devices led to an elevation in core body temperatures (SUCRA = 69.2%) and enhanced delayed recovery (SUCRA = 88.6%) as compared to the application of a single device. Furthermore, for thermal comfort, the employment of heating blankets proved to be the most effective (SUCRA = 87.8%). CONCLUSIONS: This study showed the core body temperatures and reductions in delayed recovery were greater when three heating devices were used together as compared to use one of them alone. Heating blankets was the most effective option for improving the thermal comfort of patients. Thus, clinicians should opt for appropriate heating equipment according to the type of surgery and the characteristics and needs of patients. The choice of appropriate heating equipment will ensure surgical safety, improve patient comfort, and reduce surgical risks.

[Revelation of the list of occupational diseases and diagnostic criteria for occupational diseases].

The list of occupational diseases reflecting the latest advances in the identification and recognition of occupational diseases, and providing guidance on the protection of workers' health rights and interests and the prevention, recording, notification and compensation of related occupational diseases. Diagnostic criteria for occupational diseases are an important basis for making diagnoses attributable to occupational diseases, and provide a theoretical basis for health monitoring of occupational groups and occupational hygiene supervision. This thesis starts with the definition of the occupational disease elaborates in detail the development history of list of occupational diseases in International Labour Organization (ILO) , compares the list of occupational diseases in China (2013 version) with the list of occupational diseases in international (2010 version) , and then introduces in detail the latest diagnostic standards of the major occupational diseases. And finally, it puts forward relevant suggestions on the list and diagnostic level of China's occupational diseases, so as to provide certain insights for the further improvement of the list and diagnostic standards of occupational diseases.

[Effects of modified proper digital artery island flap in repairing complex fingertip defects].

Objective: To investigate the surgical method and clinical effects of the modified proper digital artery island flap in repairing complex fingertip defects. Methods: A retrospective observational study was conducted. From January 2017 to December 2021, 15 patients (15 fingers) with complex fingertip defects, involving the pulp, nail bed, and lateral wall of the nail, who met the inclusion criteria were admitted into General Hospital of Northern Theater Command, including 11 males and 4 females, aged from 18 to 55 years. The area of the post debridement wound was from 2.5 cm×2.0 cm to 3.5 cm×3.5 cm, and all the wounds were repaired by using modified proper digital artery island flap (including 3 parts: main flap, tongue-shaped flap, and triangular flap), of which the main flap was used to cover the finger pulp defect, the tongue-shaped flap was used to cover the nail bed and the nail lateral wall defect, and the triangular flap was inserted into the edge of the finger pulp wound to cover the vessel pedicle. The range of the flap ranged from 3.0 cm×2.0 cm to 4.5 cm×3.0 cm. The wound at the donor site was repaired with full-thickness skin graft of the groin, and the donor site of the skin graft was sutured directly. After operation, the survival of the flap and skin graft as well as and the appearance of the affected finger were observed. During the follow-up, the fingertip morphology of the affected finger was observed, two-point discrimination distance of the affected finger pulp was measured, and the patients' satisfaction with the efficacy (including very satisfied, satisfied, and dissatisfied) was asked, and the affected finger function was evaluated by the total active movement (TAM) system evaluation standard recommended by American Academy for Surgery of Hand. Results: After operation, the main flaps and skin grafts in 15 patients all survived; but the incision at the edge of tongue-shaped flap in one patient healed poorly, and one patient developed venous stasis at the distal end of the tongue-shaped flap; the triangular flap at the pedicle was slightly bloated in the early postoperative period and became smooth after 2 to 3 months. Overall, two patients developed subcutaneous hematoma in their flaps. All the complications were healed by appropriate dressing change, suture removal, or compression bandaging. After operation, the appearance of the flap was full and formed a prominent fingertip shape. During the follow-up of 6 months to 5 years, the fingertips of the affected fingers were prominent and full; the two-point discrimination distance of the affected finger pulp was (8.6±1.4) mm; 8 patients were very satisfied with the efficacy, 6 patients were satisfied, and one patient was dissatisfied; the functional assessment of the affected fingers were all excellent. Conclusions: The modified proper digital artery island flap can repair complex fingertip defects involving the pulp, nail bed, and lateral wall of the nail. The operation is simple, and the shape and function of the fingertip are good after surgery.

[Establishment of hysteroscopic scoring system of chronic endometritis and correlative analysis with pregnancy outcomes of in vitro fertilization-embryo transfer in infertile patients].

Objective: To establish a hysteroscopic chronic endometritis (hCE) scoring system for patients with chronic endometritis, and observe the correlation of hCE score with in vitro fertilization-embryo transfer (IVF-ET) pregnancy outcomes in infertile women. Methods: The study retrospectively investigated the correlation of morphologic features and hCE score with pregnancy outcomes during IVF-ET in infertile women with CE (n=429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The clinical pregnancy rate and live birth rate with different score levels (1-3,4-7 and 8-14) after IVF-ET treatment were analyzed. Multivariate regression analysis was performed to adjust for confounding factors. The correlation and regression between hCE score and pregnancy outcomes was analyzed by curve fitting. Results: The age of 429 patients [M(Q1, Q3)] was 31 (29, 35) years. There were 50.6% (217 cases), 35.4% (152 cases), and 14.0% (60 cases) of patients with hCE score of 1-3, 4-7, and 8-14, respectively. The pregnancy rates of the three groups were 60.8% (132 cases), 44.7% (68 cases) and 16.7% (10 cases), P<0.001; The live birth rates were 51.2% (111 cases), 36.8% (56 cases) and 13.3% (8 cases), respectively (P<0.001). Compared with patients with hCE of 1-3, pregnancy rates in those with hCE of 4-7 and 8-14 were lower, and the OR values were 0.521 (0.342-0.793) and 0.129 (0.062-0.268). The live birth rates in patients with hCE of 4-7 and 8-14 were lower than that in patients with hCE of 1-3, and the OR values were 0.570 (0.372-0.873) and 0.162 (0.073-0.360), all P<0.05. Quadratic curve fitting results showed that clinical pregnancy rate and live birth rate decreased with the increase of hCE score. Conclusions: With the increase of hCE score, the clinical pregnancy rate and live birth rate of patients gradually decrease. hCE 4 is an important cut-off threshold significantly affecting the pregnancy outcome.

[Correlation analysis of age and microbial characteristics in saliva and feces of high-risk population of upper gastrointestinal cancer].

Objective: To explore the correlation between age and diversity and microbial composition in saliva and feces microbiota in high-risk population of upper gastrointestinal cancer. Methods: Based on the national project on early diagnosis and early treatment of upper gastrointestinal cancer, 38 participants were enrolled in Linzhou in Henan province in August 2019. The participant information was collected by questionnaire. Saliva and feces specimens were collected from each participant for 16S rRNA sequencing and bioinformatics analysis. Spearman rank correlation was used to analyze the correlation between age and α diversity (Observed ASVs and Shannon index) and relative abundance of microbiota (phyla, genera, and species) in saliva and feces. Results: The median age (age range) of 38 participants was 54 (43-60) years old, and there were 16 males (42.1%). The Observed ASVs of saliva was negatively correlated with age (rs=-0.35, P<0.05), but the observed ASVs of feces was not correlated with age. In saliva, the relative abundance of Treponema (rs=‒0.44, P<0.05), Alloprevotella (rs=‒0.42, P<0.05), and Porphyromonas (rs=‒0.41,P<0.05) were significantly negatively correlated with age. At the species level, the relative abundance of Porphyromonas endodontalis, Alloprevotella tannerae, Haemophilus influenza, Moraxella bovoculi, Prevotella sp.oral clone ID019, and Prevotella sp.oral clone ASCG10 in saliva were significantly negatively correlated with age, and the rs values were -0.50, -0.40, -0.38, -0.35, -0.33 and -0.33 (P<0.05), respectively. In feces, the relative abundance of Enterobacteria (rs=-0.35, P<0.05), Escherichia (rs=-0.33, P<0.05), and Bifidobacteria (rs=0.33, P<0.05) were correlated with age. At the species level, the relative abundance of Romboutsia sedimentorum, Citrobacter murliniae, and bacteroides uniformis in feces were correlated with age, and the rs values were -0.42, -0.37 and 0.36 (P<0.05), respectively. Conclusion: Age of the high-risk population of upper gastrointestinal cancer is correlated with the relative abundance of microbiota in saliva and feces.

[Epidemiological investigation on allergic diseases related to animal dander of cats, dogs and horses].

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ2=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ2=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.

New insight in the immune mechanisms in hyperuricemia after renal transplantation: a narrative review.

OBJECTIVE: Due to underlying allograft rejection and renal ischemia reperfusion injury (IRI) inducing renal injury, hyperuricemia (HUA) is one of the common complications after renal transplantation and may be a major contributor to reduced renal function. Currently, there are no uniform mechanisms of HUA after renal transplantation. This review aimed to figure out the immune mechanisms of HUA after renal transplantation and the molecular mechanisms of HUA-induced renal injury to provide new insights into renal function protection and prolonged survival time of grafts. MATERIALS AND METHODS: The search terms included 'Hyperuricemia', 'Renal transplantation', 'Urea acid', 'Gout' 'Graft Rejection', 'Graft Survival'. Databases including PubMed, Cochrane Library, Embase, Clinicaltrials.gov and China National Knowledge Infrastructure (CNKI) were searched for studies including mechanisms of hyperuricemia after renal transplantation from the beginning of databases to March 2022. RESULTS: Our study reviews the immune mechanisms of HUA after renal transplantation. HUA induces renal injury mainly by renal inflammation, oxidative stress, and endothelial dysfunction. IRI contributes to increased inflammation in renal grafts, mediates the recruitment of various inflammatory cell types. CONCLUSIONS: Due to underlying allograft rejection and IRI, renal transplant recipients are especially prone to HUA. HUA further reduces renal function and even graft loss. Treg targeting could be a novel therapeutic approach in renal transplantation.

Use of real-time artificial intelligence in detection of abnormal image patterns in standard sonographic reference planes in screening for fetal intracranial malformations.

OBJECTIVES: To develop and validate an artificial intelligence system, the Prenatal ultrasound diagnosis Artificial Intelligence Conduct System (PAICS), to detect different patterns of fetal intracranial abnormality in standard sonographic reference planes for screening for congenital central nervous system (CNS) malformations. METHODS: Neurosonographic images from normal fetuses and fetuses with CNS malformations at 18-40 gestational weeks were retrieved from the databases of two tertiary hospitals in China and assigned randomly (ratio, 8:1:1) to training, fine-tuning and internal validation datasets to develop and evaluate the PAICS. The system was built based on a real-time convolutional neural network (CNN) algorithm, You Only Look Once, version 3 (YOLOv3). An image dataset from a third tertiary hospital was used to further validate, externally, the performance of the PAICS and to compare its performance with that of sonologists with different levels of expertise. Furthermore, a prospective video dataset was employed to evaluate the performance of the PAICS in a real-time scan scenario. The diagnostic accuracy, sensitivity, specificity and area under the receiver-operating-characteristics curve (AUC) were calculated to assess the performance of the PAICS and to compare this with the performance of sonologists with different levels of experience. RESULTS: In total, 43 890 images from 16 297 pregnancies and 169 videos from 166 pregnancies were used to develop and validate the PAICS. The system achieved excellent performance in identifying 10 types of intracranial image pattern, with macro- and microaverage AUCs, respectively, of 0.933 (95% CI, 0.798-1.000) and 0.977 (95% CI, 0.970-0.985) for the internal validation image dataset, 0.902 (95% CI, 0.816-0.989) and 0.898 (95% CI, 0.885-0.911) for the external validation image dataset and 0.969 (95% CI, 0.886-1.000) and 0.981 (95% CI, 0.974-0.988) in the real-time scan setting. The performance of the PAICS was comparable to that of expert sonologists in terms of macro- and microaverage accuracy (P = 0.863 and P = 0.775, respectively), sensitivity (P = 0.883, P = 0.846) and AUC (P = 0.891, P = 0.788), but required significantly less time (0.025 s per image for PAICS vs 4.4 s for experts, P < 0.001). CONCLUSIONS: Both in the image dataset and in the real-time scan setting, the PAICS achieved excellent diagnostic performance for various fetal CNS abnormalities. Its performance was comparable to that of experts, but it required less time. A CNN algorithm can be trained to detect fetal CNS abnormalities. The PAICS has the potential to be an effective and efficient tool in screening for fetal CNS malformations in clinical practice. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Chemical constituents of Aglaia elaeagnoidea and Aglaia odorata and their cytotoxicity.

Two new rocaglamides, 8b-O-5-oxohexylrocaglaol (1) and elaeagnin (2), together with twelve known compounds, were isolated from the bark of Aglaia elaeagnoidea and the whole tree of A. odorata. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Cytotoxic activity against HepG2 human liver cancer cells of the isolated compounds was evaluated in vitro using the SRB assay. Three rocaglamide derivatives, dehydroaglaiastatin (13), 8b-O-5-oxohexylrocaglaol (1) and rocaglaol (5), exhibited significant effects with IC50 values of 0.69, 4.77 and 7.37 µM, respectively.

[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].

Objective: To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. Methods: A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ2 test was used for categorical variables. Results: A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ2=6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ²=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ2=4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×109/L vs. 10.5 (2.5-32.2)×109/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) µg/L vs. 0.24 (0.01-18.85) µg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions: The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Transcription factor EB related autophagy in the treatment of multiple myeloma and its mechanism].

Objective: To clarify the effects of bortezomib combined with or without siramesine on the proliferation of multiple myeloma cell lines, the expression changes of transcription factor EBC (TFEB) nuclear translocation and the level of autophagy, and to provide basis for further exploring the regulation mechanism of transcription factor TFEB on autophagy. Methods: The multiple myeloma cell lines RPMI8226 and U266 were cultured in vitro, and the multiple myeloma cells were treated with a certain concentration of bortezomib and siramesine. The changes of cell proliferation inhibition were detected by CCK-8 method. Real time PCR and Western blot were used to detect the relative expression of TFEB, autophagy-related factor LC3B, Beclin1, p62, LAMP1 mRNA and protein. Results: As the concentration of bortezomib increased and the duration of action increased, the proliferation inhibition rates of the two cell lines gradually increased (P<0.05) . The combination of the two drugs has a synergistic inhibitory effect on the proliferation of the above-mentioned multiple myeloma cell lines (P<0.05) . In the blank control group, single drug group, and combination drug group, the relative expression of TFEB mRNA and protein in the cytoplasm decreased sequentially (P<0.05) , and the relative expression of TFEB mRNA and protein in the nucleus increased sequentially (P<0.05) . The relative expression of autophagy-related factors LC3B, Beclin1, LAMP1 mRNA and protein increased sequentially, and the relative expression of p62 mRNA and protein decreased sequentially (P<0.05) . Conclusion: Bortezomib and siramesine can synergistically inhibit the growth of multiple myeloma cells, which is related to the increased autophagy expression in multiple myeloma cell lines and the expression of TFEB with nuclear translocation is also enhanced.

Correlation study between the magnetic resonance imaging features of breast cancer and expression of immune molecular subtypes.

OBJECTIVE: To investigate the correlation between breast cancer magnetic resonance imaging features and immune molecular subtypes. PATIENTS AND METHODS: A total of 129 breast cancer patients were selected as the research object. All the patients were diagnosed by histopathology. All of them had breast magnetic resonance imaging and examination data of immunohistochemical (IHC) ER, PR, HER-2, and Ki-67. The correlation of breast cancer magnetic resonance imaging features with different immune molecular subtypes was retrospectively analyzed. RESULTS: Breast cancer is divided into different molecular subtypes. There were 72 cases with Luminal A type (55.81%), 20 cases with Luminal B type (15.50%), 14 cases with HER-2+ type (HER-2 type for over-expression) (10.85%), 23 cases with TNBC type (ER, PR and HER-2 were negative) (17.84%). The magnetic resonance imaging features of breast cancer were included, the post-enhanced morphology, margins, internal enhancement features, time-signal intensity curve (TIC) and molecular subtype expression of lesions were significantly correlated with the immune molecular subtypes (C=0.602, 0.439, 0.350 and 0.407, p=0.000, 0.000, 0.006 and 0.000). Lesion morphology: Luminal A type was mainly oval, accounting for 76.39% (55/76). Luminal B type and HER-2+ type was mainly irregular, accounting for 75.00% (15/20) and 64.29% (9/14) respectively. TNBC type was mainly shown as lobulation, accounting for 60.87% (14/23). Margin of the lesion: Luminal A type was mainly smooth margin, accounting for 73.61% (53/72). Luminal B type and TNBC type were mainly irregular margin, accounting for 70.00% (14/20) and 56.52% (13/23) respectively. The margin of HER-2+ type was mainly spiculation, accounting for 64.29% (9/14). The internal enhancement features: Luminal A type was mainly even enhancement, accounting for 62.50% (45/72). Luminal B type and HER-2+ type were mainly heterogeneous enhancement, accounting for 65.00% (13/20) and 64.29% (9/14) respectively. TNBC type was mainly annular enhancement, accounting for 73.91% (17/23). TIC type: Luminal A type was mainly Type II, accounting for 66.67% (48/72). Luminal B, HER-2+ type and TNBC type was mainly Type III, accounting for 70.00% (14/20), 64.29% (9/14) and 60.87% (14/23) respectively. The clinical signs include painless breast lumps, bloody breast discharge, and orange peel-like skin changes, nipple retraction and nipple elevation. There is no significant correlation between the above signs and the expression of molecular subtypes (C=0.014, 0.129, 0.154, 0.097 and 0.057, p=0.999, 0.533, 0.447, 0.747 and 0.935 respectively), the difference is not statistically significant (p>0.05). CONCLUSIONS: The characteristics of breast cancer magnetic resonance imaging was certainly correlated with the expression of immune molecular subtypes. The breast cancer molecular subtypes can be predicted by the imaging signs, which can provide valuable information for preoperative neoadjuvant treatment of breast cancer.

[Development of a hyperkalemia risk assessment model for patients with chronic kidney disease].

Objective: To investigate risk factors for hyperkalemia among chronic kidney disease (CKD) patients and establish a risk assessment model for predicting hyperkalemia events. Methods: Clinical data of CKD patients (stage 3 to 5) hospitalized between May 2017 and June 2020 from 14 hospitals were retrospectively collected and divided into training dataset and validation dataset through balanced random sampling. Multivariate logistic regression analysis was used to analyze risk factors for hyperkalemia in CKD patients and the factors were scored. Receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Meanwhile, the cut-off value with the best sensitivity and specificity were used to verify the accuracy of the model in validation dataset. Results: A total of 847 CKD patients were enrolled and further divided into training dataset (n=675) and validation dataset (n=172). There were 555 males and 292 females, with a mean age of (57.2±15.6) years. Multivariate logistic regression analysis showed that age, CKD stage, history of heart failure, history of serum potassium ≥5.0 mmol/L, diabetes, metabolic acidosis, and use of medications that increase serum potassium levels were risk factors for causing hyperkalemia in patients with CKD. Risk assessment model was established based on these risk factors. The AUC of the ROC curve was 0.809. Using 4 as the cut-off value, the sensitivity and specificity for predicting hyperkalemia events reached 87.1% and 57.0%, respectively. Conclusion: The model established in the current study can be used for predicting hyperkalemia events in clinical practices, which offers a new way to optimize serum potassium management in patients with CKD.

[Clinical efficacy of two-staged Fowler-Stephens laparoscopic orchidopexy in the treatment of children with high cryptorchidism].

Objective: To Evaluate the clinic effect of two-staged laparoscopic Fowler-Stephens orchiopexy in the treatment of high cryptorchidism, and compare it with laparoscopic orchiopexy treatment without disconnecting spermatic vessels. Methods: A retrospective analysis was conducted on 20 cases of children with high cryptorchidism who were treated with two-staged Fowler-Stephens orchiopexy from January 2015 to April 2019 (F-S group). All the children in this group had unilateral cryptorchidism, age 6 to 18 months. The average age was 13.5 months. Seven cases were on the left side, and 13 cases were on the right side. There were 20 control children in the same age group who were treated with testicular fixation without disconnecting spermatic vessels, age 6 to 18 months. The average age was 12.5 months. Six cases were on the left side, and 14 cases were on the right side. Testicular ultrasonography and sex hormone examination were conducted before operation. F-S group met the indications for Fowler-Stephens surgical. In the first stage, the testicular vessels were doubly clipped at a site away from the testis in laparoscopic, and the second stage was scheduled about 6 months after the first stage. The children in the control group were treated with laparoscopic orchiopexy without disconnect spermatic vessels. The two groups were followed up to 6 months after the operation, and the testicular volume and sex hormone indexes of the two groups were measured. The testicular volume and sex hormones before and after the operation of the F-S group and the control group were respectively subjected to a self-control study, and a hormone comparison study was carried out between the two groups of children. Results: Both the F-S group and the control group successfully fixed the testes in the scrotum without tension during the operation. In both groups, 20 cases of testicular positions were reexamined 6 months after the operation without retraction. All the patients had a viable testis in scrotum after operation. Two of F-S group had an atrophic testis in the scrotum, and the others had a good vascularization detected on echo color doppler ultrasound. The average testicular volume of F-S group was (0.34±0.16) ml before operation and the postoperative one was (0.38±0.13) ml, P=0.089, P>0.05. In control group, the preoperative average testicular volume was (0.40±0.14) ml, and postoperative one was (0.40±0.15) ml, P=0.933, P>0.05. The testicular volume of two group had no significant difference. Sex hormone reexamination: Testosterone (T), estradiol (E2) and luteinizing hormone (LH) did not change after operation. Prolactin (PRL) in F-S group was 13.44 µg/L before operation and 12.3 µg/L after operation, PRL in control group was from 15.45 µg/L to 10.34 µg/L, P=0.732, the change of prolactin (PRL) has no significant difference. The median preoperative follicle stimulating hormone (FSH) in the F-S group was 1.18 U/L preoperatively and 1.61 U/L postoperatively; the median FSH of the control group was 1.21 U/L preoperatively and 1.1 U/L postoperatively. Compared between the two groups, the postoperative increase in the FS group was higher than that before the operation, P=0.032, P<0.05, the difference was statistically significant. The median of progesterone (PROG) in the F-S group was 0.25 nmol/L before operation and 0.17 nmol/L after operation; the median PROG of the control group was 0.56 nmol/L before operation and 0.24 nmol/L after operation. It was lower after the operation than before the operation, P=0.034, P<0.05, the difference was statistically significant. Conclusions: (1) Laparoscopic Fowler-stephens staging operation is an effective method for the treatment of patients with high cryptorchidism, and it is worthy of further promotion. (2) Disruption of spermatic cord vessels does have an impact on hormones changes. The choice of this surgical procedure should be carefully and fully evaluated.

[Increased Notch receptors induces CD8(+) T cell exhaustion in patients with prostate cancer].

Objective: To investigate Notch receptor expression in CD8(+) T cells in patients with prostate cancer, and to assess the influence of Notch signaling pathway on the function of CD8(+)T cells inpatients with prostate cancer. Methods: Forty-five patients with prostate cancer, forty-one patients with nonbacterial prostatitis, and thirty healthy controls who were hospitalized or followed-up in Shanxi Provincial People's Hospital between November 2017 and June 2018 were enrolled. CD8(+)T cells were purified, and mRNA relative levels of Notch1-4 were semi-quantified by reverse transcriptional real-time PCR. CD8(+)T cells were stimulated with Notch signaling inhibitor γ-secretase inhibitor (GSI). mRNA relative levels of perforin, granzyme B, and FasL were semi-quantified by reverse transcriptional real-time PCR. Percentages of PD-1 and CTLA-4 positive cells were investigated by flow cytometry. Direct contact and indirect contact coculture systems were set up between CD8(+)T cells and prostate cancer cell line LAPC4 cells. The influence of Notch signaling inhibition to CD8(+)T cell cytotoxicitywas assessed by measuringtarget cell death and cytokine secretion. One-Way ANOVA, LSD-t test, and paired t test was used for comparison. Results: mRNA relative levels of Notch1~4 were elevated in CD8(+)T cells from prostate cancer patients when compared with those from healthy controls and nonbacterial prostatitis patients (all P<0.05). There was CD8(+)T cell exhaustion in prostate cancer patients, which presented as decreased mRNA relative levels of perforin, granzyme B, and FasL (all P<0.000 1), as well as increased percentage of PD-1(+)CD8(+) (19.3%±5.4%) and CTLA-4(+)CD8(+)(11.7%±3.9%) cells. CD8(+)T cells from prostate cancer patients induced LAPC cell death was downregulated in direct contact coculture system (28.8%±6.4% vs 37.2%±2.6%, P=0.015). IFN-γsecretion was also reduced ((61.7±10.6)ng/L vs (88.6±20.2)ng/L, P=0.003 2). Inhibition of Notch signaling by GSI increased mRNA of perforin, granzyme B, and FasL in CD8(+)T cells from prostate cancer patients (all P<0.01), while reduced percentage of PD-1(+)CD8(+)(12.6%±2.5% vs 17.4%±4.7%, P=0.005 9) and CTLA-4(+)CD8(+) (12.0%±1.0% vs 14.1%±3.1%, P=0.011)cells. Notch signaling inhibition promoted LAPC4 cell death (34.3%±7.2%, P=0.000 2) which induced by prostate cancer derived CD8(+)T cells, and increased IFN-γ production ((88.4±33.6)ng/L, P=0.008 3). Conclusion: Elevated Notch receptors induced CD8(+)T cells exhaustion in prostate cancer patients.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.