Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

Water tank scale: a reliable method for assessing motor function after spinal cord injury in rats / 南方医科大学学报

OBJECTIVE@#To analyze the reliability of the Water Tank Scale for assessing recovery of motor function after spinal cord injury (SCI) in rats.@*METHODS@#Thirty-six adult female SD rats were randomly divided into SCI and sham-operated groups (n= 18). The recovery of the hind limb motor function was assessed using Water Tank scoring, BBB scoring, and motor-evoked potentials (MEP) at 1, 3, 5, 7, 14 and 21 days after SCI. MEP was used as the gold standard for analyzing and comparing differences between the two scoring methods.@*RESULTS@#The Water Tank scores of the rats were significantly higher than the BBB scores on day 3 (0.22±0.43 vs 0, P < 0.05) and also on days 5, 7 and 14 after SCI (0.67±0.49 vs 0.11±0.32, 4.33±1.19 vs 2.83±1.04, 8.61± 1.20 vs 7.06±1.0, P < 0.01). On day 21 after SCI, the scores of the Water Tank Scale of the rats did not significantly differ from the BBB scores (14.78±1.06 vs 14.50±1.47, P>0.05). Neurophysiological monitoring showed that both the Water Tank score and BBB score were significantly correlated with MEP latency, but the Water Tank score had a greater correlation coefficient with MEP latency (r=-0.90).@*CONCLUSION@#Compared with the BBB scale, Water Tank scoring allows more objective and accurate assessment of functional recovery of the spinal cord in early stages following SCI in rats, and can thus be used as a reliable method for assessing functional recovery of the hind limbs in rat models of acute SCI.

Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments / 中国中药杂志

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Cardiac Structural and Functional Features in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction:A Study Based on Propensity Score Matching / 中国医学科学院学报

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

Inositol 1,4,5-triphosphate receptor 3 promotes renal cyst development in autosomal dominant polycystic kidney disease / 生理学报

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.

MR-guided focused ultrasound surgery for localized prostate cancer: a preliminary investigation / 中华放射学杂志

Objective:To investigate the safety and efficacy of MR-guided focused ultrasound surgery (MRgFUS) in treating localized prostate cancer.Methods:Six patients with localized prostate cancer who underwent MRgFUS treatment from August 2020 to September 2021 in Beijing Hospital were prospectively enrolled in this study. The patients were all over 18 years old, with an average age of (68±10) years, and had not received any prior treatment for prostate cancer. Pretreatment pelvic MR and CT scans were performed to determine the region of treatment (ROT). Different urinary catheterization measures were given based on the location of the lesion. Under general anesthesia, the lesions were treated by MRgFUS using a specialized rectal ultrasound transducer on the treatment bed. The patients were followed up at 1, 3, and 6 months after treatment and annually thereafter. During follow-up, prostate-specific antigen (PSA) levels, pelvic MR scans, International Prostate Symptom Score (IPSS), International Index of Erectile Function-15 (IIEF-15) scores, and adverse events were assessed.Results:(1) All six patients underwent MRgFUS treatment for six lesions, with an average duration of (126±56) minutes, an average number of (7.3±3.2) focal ultrasound pulses per lesion, and an average non-perfusion volume of (3.8±1.1) cm 3, which covered the entire treatment target area. No treatment-related adverse events were reported. (2) The PSA levels at baseline, 1, 3, 6, and 12 months after treatment were (6.6±0.8), (3.6±1.3), (3.4±3.0), (2.5±1.7), and (2.3±1.8) ng/ml, respectively. PSA levels increased in 2 out of 6 patients during follow-up, and pelvic MR scan revealed recurrent lesions, while PSA levels continued to decrease in the remaining 4 patients, and pelvic MR scan were normal. (3) The IPSS scores at baseline, 1, and 3 months after treatment were 13.0 (4.0, 16.0), 10.0 (4.0, 12.0), and 5.0 (3.0, 6.0) points, respectively. For the three sexually active patients, the IIEF-15 scores at baseline were 40, 51, and 14 points, respectively, and IIEF-15 at 1 month after treatment were 9, 8, and 14 points, respectively, and at 3 months after treatment were 9, 66 and 26 points, respectively. (4) One patient was diagnosed with recurrence 10 months after treatment, and another patient was found to have a new lesion 6 months after treatment. Conclusions:MRgFUS might be a safe, non-invasive, and effective treatment for localized prostate cancer, but regular follow-up is vital for detecting tumor recurrence.

Preliminary study on the value of fetal MRI lung volume and mediastinal shift angle for predicting prognosis of left congenital diaphragmatic hernia / 中华放射学杂志

Objective:To explore the value of fetal lung volume and mediastinal shift angle (MSA) based on fetal MRI in predicting the prognosis of congenital diaphragmatic hernia (CDH).Methods:Fetuses with left CDH that did fetal MRI in Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine from September 2016 to January 2022 were retrospectively collected. There were 65 patients, and their gestational age was 29 (26, 35) weeks when they were diagnosed with left CDH by MRI. Observed fetal lung volume and MSA were measured based on fetal MRI, and observed/expected lung volume (o/eFLV) based on gestational age was calculated. The clinical data were collected from birth to discharge, and patients were divided into survival group and death group in case of prognosis at discharge, with 54 cases in the survival group and 11 cases in the death group. The student′s t test was used to compare the difference of o/eFLV and MSA between the survival group and the death group, and the receiver operating characteristic (ROC) curve was used to evaluate the value of o/eFLV and MSA in predicting the prognosis of left CDH. Results:The o/eFLV of the survival group was 51.5%±18.3%, higher than that of the death group (27.8%±4.4%), and the difference was significant ( t=8.29, P<0.001). The MSA of the survival group was 33.1°±1.2°, lower than that of the death group (41.8°±2.7°), and the difference was significant ( t=-11.15, P<0.001). The area under the ROC curve (AUC) of o/eFLV to predict the fetal survival or death was 0.939 (95%CI 0.851-0.983), the cutoff value was 33.8%, the sensitivity was 100%, the specificity was 88.9%. The AUC of MSA was 0.998 (95%CI 0.941-1.000), the cutoff value was 37.2°, the sensitivity was 100%, the specificity was 98.2%. Conclusions:The o/eFLV and MSA that were measured based on fetal MRI can effectively predict the fetus′s prognosis with left CDH.

Arthroscopic side-to-side repair of transtendinous rotator cuff tears with remnants preserved / 中华创伤骨科杂志

Objective:To evaluate the clinical efficacy of arthroscopic side-to-side suture with remnants preserved in repair of transtendinous rotator cuff tears.Methods:A retrospective study was conducted to analyze the data of 17 patients who had been treated by arthroscopic side-to-side suture with remnants preserved for transtendinous rotator cuff tear caused by trauma at Sports Medicine Center, The Second Hospital Affiliated to Inner Mongolia Medical University from January 2017 to January 2020. There were 11 males and 6 females with an age of (47.9±8.3) years and a duration from injury to surgery of (50.4±21.3) d. Recorded were range of motion and muscle strength of the shoulder, University of California at Los Angeles (UCLA) shoulder function score, Constant-Murley shoulder function score, visual analogue scale (VAS) pain score, re-tears and complications before operation and at the last follow-up.Results:The 17 patients were followed up for (16.5±3.5) months after operation. Retear of the rotator cuff occurred in 2 patients after operation while MRI showed good healing of the rotator cuff in the other patients with no such postoperative complications as infection or wound dehiscence. At preoperation and the last follow-up, respectively, the range of shoulder flexion was 152.9°±8.5° and 172.4°±5.6°, the abductor muscle strength 3.5 (2.6, 4.1) kg and 6.9 (6.3, 8.3) kg, the external rotator muscle strength (3.8±1.0) kg and (5.9±1.6) kg, the internal rotator muscle strength 3.9 (3.4,4.7) kg and 5.2 (4.5,5.9) kg, the UCLA score (13.2±1.9) points and (30.9±2.4) points, the Constant score (40.1±2.8) points and (86.1±4.6) points, and the VAS score (6.7±0.8) points and (0.9±0.6) points, all showing a significant difference between preoperation and the last follow-up ( P<0.05). Conclusion:In repair of transtendinous rotator cuff tears, arthroscopic side-to-side suture with remnants preserved can lead to significantly improved clinical outcomes in range of motion, muscle strength, functional recovery and pain relief.

Giant fibroma of left ventricular apex with T wave inversion: 2 cases report and literature review / 中国综合临床

Objective:To investigate the clinical features, diagnostic methods and treatments of left ventricular apical fibroma.Methods:The clinical manifestations, ECG, imaging features and treatment plans of 2 patients with giant fibroma of left ventricular apex diagnosed in September 2020 and May 2022 were analyzed retrospectively, and the related literature was reviewed.Results:Both patients had slight chest distress and discomfort after activities. The ECG showed T-wave inversion of different degrees, which were misdiagnosed as “myocarditis” and “coronary heart disease” respectively. The cardiac magnetic resonance imaging and echocardiography showed left ventricular apical mass. Coronary artery stenosis was not found in coronary angiography. One patient required conservative treatment, and there was no significant change in clinical symptoms and tumor size in the follow-up for half a year; Another patient underwent cardiac mass removal, and the pathological examination after operation confirmed that it was cardiac fibroma, and there was no recurrence in the follow-up 2 years.Conclusion:Fibroma of left ventricular apex is a rare cardiac tumor, which is easy to be missed and misdiagnosed, and is one of the rare causes of T-wave inversion. Cardiac magnetic resonance imaging, CT and echocardiography are commonly used imaging methods to diagnose cardiac fibroma, and surgical resection is an effective treatment.

Analysis of 7 cases of delayed diagnosis of primary upper tract urothelial carcinoma with calculi / 现代泌尿外科杂志

【Objective】 To reduce the misdiagnosis rate by analyzing the clinical data of patients with primary upper tract urothelial carcinoma (UTUC) complicated with calculi. 【Methods】 Clinical data of 7 UTUC with calculi patients treated during Sep.2018 and Apr.2022 were retrospectively analyzed, including general data, time from visit to diagnosis, imaging data, urine exudation cytological results, surgical methods, pathological stages and follow-up data. 【Results】 The ratio of male to female was 3∶4, and the mean age was 66.4 (55-72) years. The initiate imaging examination results only showed calculi, but did not indicate suspicious tumor (including 1 case with missing data). The median time from the first visit to diagnosis was 12 months (5-36 months). Of all 7 cases, 2 (2/4) were clinically diagnosed by enhanced CT, 3 (3/4) by MRI, and 2 (2/7) by positive urine exudation cytology. All patients received surgical treatment. Postoperative pathology showed 85.71% (6/7) were high-grade UTUC. Postoperative staging was T1N0M0 in 4 cases, T3N0M0 in 2 cases, and T4N2M0 in 1 case. Adjuvant chemotherapy was conducted in 2 cases. During the median follow-up of 12 months (6-41), 1 case developed multiple systemic metastases in month 9, while the other cases had no recurrence or metastasis. 【Conclusion】 For UTUC patients without obvious filling defect on imaging, especially when ipsilateral calculi were complicated, misdiagnosis should be alerted for timely treatment and better prognosis.

Classification, Diagnosis and Management Status of Carbohydrate Metabolic Rare Disorders / 罕见病研究

Approximately 30%-40% of rare diseases are related to the endocrine and metabolic system, and abnormal metabolism of carbohydrate accounts for a significant proportion among others. Carbohydrate metabolic rare disorders often develop insidiously. The clinical symptoms of these disorders sometimes overlap with common diseases. Therefore, delayed diagnosis, misdiagnosis, and mismanagement happen often. The diagnosis and treatment of carbohydrate metabolic rare disorders is usually difficult in clinical practice. Efficient and practical screening models, identification of specific clinical features and biochemical changes, and genomic sequencing are critical to improve diagnostic efficiency. Most carbohydrate metabolic rare disorders are still lack in effective and targeted therapies. So, the symptomatic treatment is still main practice. The targeted medications and gene therapies based on precision diagnosis are directions for the diagnosis and management of rare disorders of carbohydrate metabolism in the future. In this paper, we classify the carbohydrate metabolic rare disorders based on their causes. We also discuss the current status and prospective of diagnosis and management of those diseases.

Analysis of ABO gene mRNA expression in peripheral blood of patients with acute myeloid leukemia / 中国输血杂志

【Objective】 To investigate the expression characteristics of ABO gene mRNA in peripheral blood of patients with acute myeloid leukemia. 【Methods】 The RNA-seq data of acute myeloid leukemia in TCGA database and the whole blood RNA-seq data in GTEx database were downloaded. The difference of ABO gene mRNA expression between acute myeloid leukemia and GTEx whole blood samples was analyzed by R software, and the relationship between ABO gene mRNA expression and DNA methylation, immune infiltration and prognosis was analyzed. 【Results】 The expression level of ABO gene mRNA in acute myeloid leukemia(median: 1.333, P25: 3.654, P75: 0.401)was significantly lower than that in the control group(median: 3.576, P25: 3.747, P75: 3.470)(P<0.001). The expression level of ABO gene mRNA in acute myeloid leukemia was negatively correlated with the methylation of + 82(r=-0.249, P<0.001), + 618(r=-0.268, P<0.001), + 1 080(r=-0.105, P<0.001) and + 1 409(r=-0.210, P<0.001) at downstream of transcription start site, and positively correlated with the immune infiltration of nine types of immune cells (B cells, CD8 T cells, Cytotoxic cells, pDC, T cells, T helper cells, Tcm, Tfh and Treg) (P<0.001). There was no significant difference in overall survival between patients with high (median survival time: 366 days, confidence interval: 304-731 days) and low (median survival time: 731 days, confidence interval: 335-1 402 days) expression of ABO gene mRNA in acute myeloid leukemia (P>0.05). 【Conclusion】 The mRNA expression of ABO gene in peripheral blood of patients with acute myeloid leukemia is decreased, which is associated with DNA methylation of the first intron of ABO gene and immune infiltration, but not with the prognosis.

Epidemiological characteristics of newly diagnosed occupational pneumoconiosis in Guangdong Province from 2011 to 2020 / 中国职业医学

Objective To analyze the epidemiological characteristics of newly diagnosed occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis") in Guangdong Province from 2011 to 2020. Methods Clinical data of newly diagnosed pneumoconiosis in Guangdong Province from 2011 to 2020 was collected from the “Health Hazards Monitoring Information System” under “China Disease Prevention and Control Information System”. The distribution of the cases was analyzed retrospectively. Results A total of 2 731 cases of newly diagnosed pneumoconiosis were reported from 2011 to 2020 in Guangdong Province, with cases at stages Ⅰ,Ⅱ, and Ⅲ accounting for 61.6%, 23.8%, and 14.6%, respectively. Except for talc pneumoconiosis, 12 other types of pneumoconiosis were reported. The top three incidence of diseases were silicosis, other pneumoconiosis, and welder's pneumoconiosis, accounting for 58.8%, 22.0% and 11.0%, respectively. Males accounted for 97.5%, and females 2.5%. The median age of onset was 47 years old. The median dust exposure duration was 9.8 years, with 19.4% of cases having a dust exposure duration less than 5.0 years. And 80.7% of the cases were distributed in the Pearl River Delta region. The industries with the new cases were mainly the manufacturing (accounting for 69.4%), and 34.8% of cases were found in private limited liability companies. Cases in medium- and small-sized enterprises accounted for 35.7% and 34.3% respectively. Conclusion Silicosis, other pneumoconiosis, and welder's pneumoconiosis are predominant in Guangdong Province. The prevention and control of pneumoconiosis should focus on small- and medium-sized private enterprises in the concentrated manufacturing industry in the Pearl River Delta region.

Estimation of the effective radiation dose for tunnel construction workers / 中国职业医学

Objective To analyze and set up the effective dose of different ionizing radiation for tunnel construction workers. Methods A total of five tunnels constructed using drilling and blasting methods were selected as the research subjects using the convenient sampling method. The workplace γ radiation effective dose, radon concentrations, and radioactive activity concentrations were detected, and on-site surveys were conducted to estimate the internal and external irradiation doses and total effective doses for workers in different work sites. Results Radiological hazards in tunnels constructed using drilling and blasting methods included radon and its progeny, γ radiation, radioactive dust (uranium-238, radium-226, thorium-232, and potassium-40) and others. The average total effective dose of ionizing radiation exposure for tunnel construction workers was (6.730 1±1.541 1) mSv. The average dose of radon and its progeny was (6.163 0±1.512 8) mSv, radioactive dust was (0.014 6±0.009 1) mSv, γ radiation was (0.552 6±0.138 7) mSv. The dose of radioactive dust of radon and its progeny was 0.24%. Radon and its progeny contributed more to the radioactive dose than radioactive dust and γ radiation (all P<0.05). Among all the radioactive dusts, the dose contribution ranked from highest to lowest was thorium-232, uranium-238, and radium-226. Conclusion For tunnel construction workers, the largest contribution to the effective dose of ionizing radiation exposure is from radon and its progeny for internal irradiation, followed by γ radiation for external irradiation. The contribution of radioactive dust to internal irradiation dose can be considered negligible.

Causal Relationship Between Acromegaly and Colon Cancer: A Two-sample Mendelian Randomization Study / 肿瘤防治研究

Objective To determine the causal relationship between acromegaly and colon cancer by using two-sample Mendelian randomization. Methods Genetic loci closely related to acromegaly in the whole genome-wide association study (GWAS) were selected as tool variables, and the genetic data of colon cancer from different GWASs were analyzed by two-sample Mendelian randomization (MR).The inverse variance weighting method (IVW) of the random effect model was used for analysis, and MR-weighted median and MR-Egger methods were used to supplement the analysis. Results were presented as OR values. Results Four SNPs closely related to acromegaly were obtained as tool variables, and the multiplicity test of tool variables showed that P=0.59.Three methods were used to estimate causal effects.The IVW analysis were OR=1.00(0.99-1.001) and P=0.42;the MR-Egger analysis results were OR=1.00(0.99-1.001) and P=0.42;and the Weighted median analysis results were OR=1.00(1.00-1.001) and P=0.03.The sensitivity test showed that the confidence interval of the tool variable SNP passed through 0, indicating the robustness of the MR results. Conclusion Acromegaly is not an independent risk factor for colon cancer.

The association between the TyG index and the number of coronary artery lesions in patients with stable coronary artery disease / 中华全科医师杂志

Objective:To analyse the association between triglyceride glucose (TyG) index and the number of coronary artery lesions in patients with stable coronary artery disease.Methods:It was a cross-sectional study. Patients with stable coronary artery disease who were admitted to Zhongshan Hospital, Fudan University from 1st January 2019 to 30th April 2020 for percutaneous coronary intervention (PCI) were selected. We collected general clinical information and laboratory results from the enrolled patients, then calculated the TyG index. We evaluated coronary artery lesions by coronary angiography and analysed the factors associated with the number of coronary artery lesion branches by the logistic regression model.Results:A total of 832 patients were included in this study, 641 (77.0%) were male, the age was (64.6±11.5) years. The mean TyG index was 8.78. Patients with the TyG index≥8.78 were included in the high TyG index group (411 patients), and those with the TyG index<8.78 were included in the low TyG index group (421 patients). Compared with the low TyG index group, the high TyG index group had the higher body mass index and diastolic blood pressure, more smokers and diabetes mellitus, younger age of onset of coronary heart disease (all P<0.05), and a lower proportion of patients using statins ( P=0.027). Compared with the low TyG index group, the high TyG index group had the higher levels of erythrocyte count, hemoglobin, white blood cell count, albumin, urea nitrogen, uric acid, fasting blood glucose, HbA1c, triglyceride, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, apolipoprotein E, and C-reactive protein (all P<0.05). However, the levels of high density lipoprotein, apolipoprotein A1 and apolipoprotein A were lower in the high TyG index group than those in the low TyG index group (all P<0.05). The number of coronary artery lesions in patients in the high TyG index group was 2.35±0.91, more than the low TyG index group 2.10±0.95 ( P<0.001).After adjusting for the other factors, multivariate logistic regression analysis showed that male, smoking history (smoking cessation or smoking), TyG index and troponin T levels were independently positively associated with the number of coronary artery lesions (all OR>1, P<0.05), while ApoA1 was independently negatively associated with the number of coronary artery lesions ( OR=0.140, P=0.007). Conclusions:TyG index is positively associated with the number of coronary artery lesions in patients with stable coronary artery disease.

Related factors of three-vessel disease in patients with stable coronary artery disease / 中华全科医师杂志

Objective:To analyze the risk factors of three-vessel disease (TVD) in patients with stable coronary artery disease (SCAD).Methods:The clinical data of 447 patients with SCAD diagnosed in Zhongshan Hospital from May 2019 to April 2020 were retrospectively analyzed, including 108 cases with the single-vessel disease (SVD), 136 cases with the two-vessel disease, and 203 cases with three-vessel disease. The general data and hematological indexes were compared between patients with SVD and those with TVD; the related factors for TVD in SCAD patients were analyzed with univariate and multivariate logistic regression.Results:There were 244 males (78.5%) and 67 females (21.5%) with a median age of 57 years (64, 69). Univariate analysis showed that there were significant differences in diabetes history ( χ2=7.75, P=0.005), uric acid ( Z=-2.10, P=0.036), glycosylated hemoglobin ( Z=-2.77, P=0.006) and high density lipoprotein cholesterol (HDL-C) ( Z=-2.99, P=0.003) levels between SVD and TVD groups. Multivariate analysis showed that the high level of blood uric acid ( OR=1.01, 95% CI: 1.00-1.01, P<0.05) and the low level of HDL-C ( OR=3.29, 95% CI:1.23-8.85, P<0.05) were related risk factors of TVD. Conclusion:High blood uric acid level and low HDL-C level are related factors for TVD in patients with SCAD.

Safety and efficacy of Rezūm water vapor thermal therapy system in the treatment of benign prostatic hyperplasia / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of Rezūm Water Vapor Thermal Therapy system in the treatment of patients with benign prostatic hyperplasia (BPH).Methods:The clinical data of 22 patients with benign prostatic hyperplasia treated with Rezūm Water Vapor Thermal Therapy system in Boao Yiling Life Care Center in Hainan from December 2020 to January 2021 were retrospectively analyzed, with age of (61.0±5.9) years, prostate volume of (43.7±8.4) ml. international prostate symptom score (IPSS) of (19.3±3.7), quality of life (QOL) score of (4.2±0.8), maximum urinary flow rate (Q max) of (11.9±3.4) ml ml/s, and residual urine volume (PVR) of (14.0±19.0). For 19 patients with sexual life, the International Index of Erectile Function Questionnaire-5 (IIEF-5) were 17.0±5.5, the Men's Sexual Health Questionnaire-Ejaculatory Dysfunction Score (MSHQ-EjD) ejaculatory function score were 10.0±3.2, and the ejaculatory satisfaction score were 1.5±1.0. Twenty-two patients underwent Rezūm Water Vapor Thermal Therapy under intravenous anesthesia (general anesthesia without intubation) in the dorsal lithotomy position. The Rezūm system consisted of reusable thermal steam treatment device and disposable prostate thermal steam treatment instrument. The thermal steam treatment device used radiofrequency energy to heat sterile distilled water, generating high-temperature steam at 103℃. In a 9-second timeframe, the tissue temperature within each treatment area was raised approximately 70℃, causing cell death and resulting in a shrink in prostate tissue volume. The disposable prostate thermal steam treatment instrument could be inserted through a cystoscope and had a retractable needle tip that extends to a length of 10.25 mm. The needle tip had 12 evenly distributed holes arranged in three rows of four holes each, with a spacing of 120° between rows, allowing for even diffusion of thermal steam along the circumference. The patient was placed in a lithotomy position, and the disposable prostate thermal steam treatment instrument was used to examine the prostate, urethra, and bladder via cystoscopy, assessing the lateral lobes and median lobe of the prostate. The tissue spacing within each field of view of the treatment instrument is 0.5 cm, and the distance from the bladder neck to the verumontanum is calculated. The first needle was injected at 3 o’clock along the left lobe, withdrawing 2 fields of view each time. During the release of thermal steam, the needle tip was positioned perpendicular to the prostate urethral mucosa, and each needle injection delivered 0.42 ml of sterile distilled water-formed thermal steam into the prostate tissue. The thermal steam injection lasted for 9 seconds, followed by a 2-3 seconds waiting period before retracting the needle tip. One needle was injected per 2 fields of view, progressing towards the proximal urethra of the verumontanum. The same method was used to treat the right lobe. For cases with significant median lobe enlargement, two fields of view were retracted at the bladder neck, and the needle was inserted at a 45° angle. The second needle was injected at intervals determined by the extent of median lobe enlargement. Each puncture point was observed for no significant bleeding, and the instrument was then removed, with an F16/F18 silicone catheter left in place. The operative time as well as indwelling catheter time were recorded. The clinical parameters such as IPSS, QOL, prostate volume, Qmax, PVR, QOL, IIEF-5 and MSHQ-EjD at preoperative and 12 to 22 weeks post operation were compared. Adverse events from the Rezūm procedure to 12-22 weeks postoperatively were recorded. Results:All the operations were successfully completed. The operation time of Rezūm system was 3.9±1.6 min, and the indwelling catheter time after operation was 4.8±1.1 days. The IPSS scores of 22 patients at 12-22 weeks after operation were 4.4±3.3, whose reduction was 14.9±4.4 compared with these at baseline( P<0.01). The PV was (37.7±8.4)ml, Qmax was (25.5±9.6)ml/s, PVR was (6.2±8.1)ml, and QOL was 1.6±0.9, all demonstrating statistically significant differences compared to preoperative values ( P<0.05). Among the 19 cases with sexual activity, the IIEF-5 score was 20.4±3.2, and the ejaculatory function score of MSHQ-EjD was 13.1±3.1, both showing statistically significant differences compared to preoperative scores ( P<0.05). The ejaculatory satisfaction score of MSHQ-EjD was 1.1±0.5, and there was no statistically significant difference compared to preoperative scores ( P>0.05). None of the 22 cases required medication or further surgical treatment for BPH after surgery. There were no urethral injuries, rectal or bladder perforations during the surgeries, and no severe complications such as rectal fistula or bladder neck contracture occurred postoperatively. There were no deaths reported. Postoperative discomfort in the urethra occurred in 19 cases, urethral pain in 8 cases, hematuria in 15 cases, poor sleep quality in 2 cases, and constipation in 1 case, all of which resolved within 7 to 10 days after surgery. Erectile dysfunction and retrograde ejaculation occurred in one case each at 4 to 5 weeks postoperatively but did not reoccur thereafter. Prostatitis and nodular hyperplasia of the middle lobe of the prostate occurred in one case each at 21 weeks and 25 weeks postoperatively, respectively, and no treatment was administered. Conclusions:In the real world, the short-term overall effect of Rezūm Water Vapor Thermal Therapy system in the treatment of benign prostatic hyperplasia is satisfactory, which shows good efficacy and safety.

Comparison of complications and analysis of factors affecting renal function decline after laparoscopic radical cystectomy with different urinary diversion methods / 中华老年医学杂志

Objective:To compare the complications associated with various urinary flow diversion methods and identify the factors that contribute to the decline in renal function after radical total cystectomy for myoinfiltrating urothelial carcinoma.Methods:This study conducted a retrospective analysis on the clinical data of 46 patients with pathologically confirmed muscle-invasive bladder cancer.The patients underwent laparoscopic radical cystectomy with either ileal conduit diversion(n=21)or ureterocutaneous diversion(n=25)between January 2017 and December 2021.Perioperative data, postoperative pathology, postoperative complications, and follow-up results were compared between the two groups.Results:The study found significant differences between the two groups in terms of age[(67±6)years vs.(73±8)years, t=3.132, P=0.003], Charlson comorbidity index adjusted for age[(3.80±1.15) vs.(4.52±1.03), t=2.223, P=0.031], prognostic nutritional index[(48.81±5.74) vs.(43.64±4.74), t=3.347, P=0.002], operation time[(449±108)minutes vs.(326±130)minutes, P=0.001]], hospital stay[(20.1±11.1)days vs.(13.3±5.2)days, t=2.762, P=0.008], proportion of Clavien grade 3 or higher complications within 3 months after surgery(4/21 vs 0/25, χ2=2.105, P<0.05), and proportion of stoma-free patients(18/21 vs.5/25, χ2=6.373, P<0.01). According to Logistic multivariate analysis, perioperative blood transfusion and urinary tract infection were identified as independent risk factors for renal function decline 12 months after surgery.Escherichia coli was found to be the most common bacteria cultured from urinary tract infections in both groups after surgery. Conclusions:Laparoscopic radical cystectomy with ureterocutaneous diversion offers benefits such as shorter hospital stays and fewer perioperative complications for older and frail patients.However, a higher proportion of patients may require ureteral stenting.It is important to note that perioperative blood transfusion and urinary tract infection are major risk factors for renal function decline following radical cystectomy.

The preliminary experience of immediate radical prostatectomy after the diagnosis of prostate cancer by targeted prostate biopsy combined with intraoperative frozen section / 中华老年医学杂志

Objective:To investigate the practicality and safety of performing a radical prostatectomy(RP)shortly after the diagnosis of prostate cancer using a combination of prostate targeted biopsy and intraoperative frozen section.Methods:Prospective enrollment was conducted for patients suspected of having prostate cancer based on abnormal prostate specific antigen(PSA)levels.The inclusion criteria for the study were as follows: patients aged 80 years or younger with an ECOG score of 1 or lower.Prior to biopsy, patients underwent both prostate magnetic resonance imaging(MRI)and prostate specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)to determine the likelihood of prostate cancer with clinical stages within T 2-3aN 0M 0.In order to be included in the study, patients must agree to receive RP after their prostate cancer diagnosis has been confirmed by biopsy.All enrolled patients underwent a targeted prostate biopsy, consisting of 1-2 cores.These specimens were then examined through frozen section analysis.For patients diagnosed with prostate cancer through intraoperative frozen section pathology, RP was immediately performed.In this study, transperineal prostate targeted+ systematic biopsy was utilized for patients with undiagnosed prostate cancer.Additionally, routine pathological examination of specimens was conducted.The study analyzed the baseline data, surgical conditions, pathological results, and follow-up information of patients in a descriptive manner. Results:Seven patients, ranging in age from 54 to 77 years with a mean age of 66.7 years, were enrolled in the study.Their mean PSA level was 12.668 μg/L, ranging from 4.359 to 22.195 μg/L.Of these patients, 4 had a PI-RADS score of 4 and 3 had a score of 5.The maximum diameter of the index lesion was 1.3 cm, ranging from 0.5 to 2.2 cm.PSMA PET/CT scores were 4 in 1 case and 5 in 6 cases.The index lesions detected by PSMA PET/CT were consistent with those detected by MRI, and the maximum standardized uptake value(SUVmax)was 15.7, ranging from 5.3 to 39.4.Prostate cancer was diagnosed through targeted biopsy and intraoperative frozen section pathology.Four cases had a Gleason score of 3+ 3=6, while one case had a Gleason score of 3+ 4=7, another had a score of 4+ 3=7, and the last had a score of 4+ 4=8.All patients underwent RP treatment immediately after the prostate cancer diagnosis.Only one patient had slight adhesion at the apex of the prostate, while the other six patients were evaluated by surgeons as having no obvious adhesion at the apex.All surgeries were completed successfully, with a mean operation time of 149.7(ranging from 108 to 255)minutes.After RP, whole mount pathology results indicated that all cases were prostate adenocarcinoma, with a Gleason score of 3+ 4=7 in four cases and 4+ 3=7 in three cases.The pathological stages were pT2 in three cases and pT3a in four cases, with five cases having negative surgical margins and two cases with positive surgical margins.During the study, all patients were monitored for a period of 5.4 months(ranging from 3 to 7 months)and no complications of Clavien Dino≥Ⅰ were observed.PSA levels were measured at 6 weeks and 3 months after surgery, with readings of 0.020 μg/L(ranging from 0 to 0.079 μg/L)and 0.016 μg/L(ranging from 0 to 0.087 μg/L), respectively.No hormonal therapy or radiotherapy was administered during this time.Four patients were able to recover from urinary continence.Conclusions:Based on a combination of MRI and PSMA PET/CT, it is both safe and feasible to promptly perform RP following the diagnosis of prostate cancer through targeted biopsy for index lesions, along with intraoperative frozen section.