Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis / 中华医学杂志(英文版)

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Analysis of ocular biometric parameters in Tibetan patients with age-related cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the differences of ocular biometric parameters of age-related cataract between Tibetan and Han ethnic groups, and to analyze the distribution characteristics of ocular biometric parameters in Tibetan cataract patients.METHODS:Retrospective cohort study. A total of 661 patients(1 030 eyes)with age-related cataract confirmed in the hospital between January 2019 and December 2020 were enrolled. The parameters of axial length, anterior chamber depth, keratometry, corneal astigmatism and astigmatic axis were measured by IOL Master 500 in 483 cases(739 eyes)of Tibetan age-related cataract patients and 178 cases(291 eyes)of Han patients.RESULTS:The axial length, anterior chamber depth and corneal astigmatism of the Tibetan patients with age-related cataract were 23.33(22.81, 23.86)mm, 3.04(2.79, 3.30)mm and 0.73(0.47, 1.07)D. The mean keratometry was 43.89±1.35 D. The results indicated that Tibetan cataract patients had shorter axial lengths and smaller keratometry compared to Han patients(all P<0.05). Age in Tibetan patients was negatively correlated with axial length and anterior chamber depth, and positively correlated with keratometry(all P<0.05). Tibetan male patients had longer axial lengths, deeper anterior chambers, and flatter corneas compared to female patients(all P<0.05).CONCLUSION:There were differences in ocular biometric parameters between age-related cataract patients of Tibetan and Han ethnicities. The distribution of ocular biometric parameters in Tibetan cataract patients varied across different age groups and gender groups.

Association of diabetic retinopathy with anxiety and depression / 国际眼科杂志(Guoji Yanke Zazhi)

As society advances and living standards improve, there is a growing emphasis on the impact of mental health on illness and the interaction between them. Diabetes mellitus is one of the most common underlying diseases, and it is often accompanied by depression and anxiety. There are also many complications of diabetes, such as diabetic retinopathy(DR). DR is the leading cause of vision loss in diabetes. Vision loss inevitably increases anxiety and/or depression, which in turn may directly or indirectly affect the treatment or progression of patients with DR. This article reviews how to determine the anxiety and depression status of patients with DR, related assessment tools and methods, and their interaction with the treatment of DR. The interaction of anxiety-depressive states with DR treatment was also discussed. This review aims to raise awareness of the mental health of patients with DR, enhance doctor-patient communication and build doctor-patient trust, thus enhancing treatment adherence and clinical efficacy for individuals with DR and helping them to improve the quality of life.

Effect of cognitively engaging physical activity on developing executive function of children and adolescents: a systematic review based on ICF / 中国康复理论与实践

ObjectiveTo systematically review the intervention effect of cognitively engaging physical activity (CEPA) on executive function of children and adolescents. MethodsLiteratures in Chinese and English were retrieved from databases of Web of Science, PubMed, Medline, EBSCO and CNKI, from the establishment to November 30th, 2023. According to the inclusion and exclusion criteria, the literatures that met the requirements were screened, and their quality was evaluated and systematically reviewed. ResultsA total of 15 literatures were included, published between 2014 and 2023, from eight countries, involving 1 806 subjects aged four to 16 years. The average score of PEDro scale was 6.6. The intensity of the CEPA intervention ranged from 64% to 93% HRmax, the duration of a single session ranged from ten to 60 minutes, and the frequency of the intervention was two to five sessions a week, for four to 24 weeks. Specific forms of CEPA included football, basketball and floorball combined with cognitive tasks; running, jumping, squatting, sitting, spinning and balancing combined with cognitive tasks; and exergaming combined with cognitive tasks. Eleven researches showed positive effects of CEPA intervention on at least one component of executive function. However, six of the seven researches involving working memory failed to verify the positive effects. Twelve researches compared the intervention effects of CEPA and rutine exercise or regular physical education classes, and nine researches found that CEPA was more effective on executive function. ConclusionThe CEPA is effective on the executive function of children and adolescents, specifically on cognitive flexibility; it shows inconsistent effects on inhibitory control, and its effect on working memory has not been verified. The intervention types of CEPA are divided into ball games combined with cognitive tasks, basic motor skills training combined with cognitive tasks, and exergaming combined with cognitive tasks.

Chronic hepatitis B virus infection and metabolic associated fatty liver disease： The known and unknown aspects / 临床肝胆病杂志

Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.

Thoughts on Ethical Collaborative Review and Management of Multi-center Clinical Research / 中国医学伦理学

For multi-center clinical research, how to ensure the quality of ethical review and improve the efficiency of ethical review through cooperation among centers is an important direction for clinical research management departments and research parties to explore. By combing and analyzing the existing pattern of multi-center ethical review at home and abroad, combining the current situation of the ethical review and management development in China, taking cancer clinical research as the breakthrough point, it was advocated to establish a cooperative review led by professional institute in domestic, on the basis of extensive and in-depth training exchanges and effective communication on the same platform, collaborative review, ensure quality and efficiency, so as to promote and implement the "mutual recognition" of ethical review. Then, this paper further put forward the concept of "whole-process linkage" in the ethical management process of multi-center clinical research, and pointed out that all research parties should clarify their responsibilities, enhance their awareness and ability, and jointly and comprehensively implement the protection of subjects among clinical researchers.

Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples / 中华医学遗传学杂志

OBJECTIVE@#To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies.@*METHODS@#A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups.@*RESULTS@#Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2 = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2 = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2 = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up.@*CONCLUSION@#The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

Formation of Hyperprogression of Immunotherapy from Perspective of "Yang Deficiency and Toxin Knot" and Role of "Five Views on Differentiation and Treatment" Intervention / 中国实验方剂学杂志

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

Exploring the Co-occurrence and Treatment of Tumors and Psycho-Cardiological Diseases Based on the Concept of “Diagnosing and Treating Diseases According to Syndromes” / 中医杂志

The co-occurrence of tumor and psycho-cardiological diseases， affecting both the physical and mental aspects of patients， is a common clinical condition that is closely related to tumor treatment and prognosis. Exploring its underlying mechanism and treatment methods can bring new ideas and strategies for clinical treatment. It is believed that heart-kidney yang deficiency is one of the common core mechanisms of psycho-cardiological diseases. Stagnation of heat and toxins is a core mechanism for tumor formation and metastasis. Additionally， cancer and drug toxicity contribute to the development of psycho-cardiological disease by impairing lung circulation. Cancerous toxins can damage the blood vessels， resulting in a diminished vitality in the heart of blood vessels. Simultaneously， lung qi failing in dispersing impairs the downward movement and causes stagnation in the heart of spirit . This process ultimately leads to the development or exacerbation of psycho-cardiological diseases. The author explores the diagnosis and treatment approach based on the “diagnosing and treating diseases according to syndroms” concept， focusing on related syndrom identification and treatment. The process begins with pattern identification， followed by comprehensive analysis of data gained by four diagnostic methods to clearly understand the core pathogenesis and basic treatment principles. After pattern identification， the focus shifts to recognizing the disease and providing additional evidence to support the diagnosis. Special attention is paid to adjusting the use of medication based on the disease's characteristics. This approach aims to achieve precise treatment for tumors and psycho-cardiological diseases， reducing the side effects of multiple medications， therefore to provide guidance for clinical application.

Research progress of application of transcatheter aortic valve replacement in the bicuspid aortic valve stenosis / 中国胸心血管外科临床杂志

@#Patients with bicuspid aortic valve (BAV) are characterized by asymmetric anatomy, severe calcification and combined aortic dilatation. Compared with tricuspid aortic valve stenosis patients, patients with BAV stenosis confront with greater surgical risks in transcatheter aortic valve replacement (TAVR), including paravalvular leak, aortic valve rupture, coronary artery obstruction, atrioventricular block and so on. However, with the advent of new generation of prosthetic valves and optimization of surgical strategies, several studies have shown that TAVR is safe and effective in the treatment of BAV stenosis. Therefore, we aim to provide an overview of the use of TAVR in patients with BAV stenosis.

Correlation between serum nesfatin-1, apelin and HO-1 levels and the severity of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To analyze the correlation between serum nesfatin-1, apelin and heme oxygenase-1(HO-1)levels and the severity of diabetic retinopathy(DR).METHODS:Totally 100 patients with type 2 diabetes mellitus(T2DM)who were admitted to the hospital from September 2020 to September 2022 were selected. They were divided into non-DR(NDR)group(35 cases), nonproliferative DR(NPDR)group(33 cases)and proliferative DR(PDR)group(32 cases)according to the condition of fundus lesions. Another 30 healthy individuals who received health check-ups in the hospital during the same period were selected as the control group. Serum nesfatin-1, apelin and HO-1 levels in each group were detected, and panretinal ischemia index(ISI)was evaluated.RESULTS:Serum nesfatin-1 and HO-1 levels in the T2DM patients were lower, and apelin level was higher as compared with the control group. The levels of nesfatin-1 and HO-1 in the PDR group were the lowest, while the apelin level was the highest. Panretinal ISI in the PDR group was higher than that in the NPDR group(4.56±0.57 vs. 2.05±0.29, P&#x0026;#x003C;0.05). Correlation analysis found that serum nesfatin-1 and HO-1 levels were negatively correlated with panretinal ISI in patients with DR, while apelin level was positively correlated with panretinal ISI. The receiver operator characteristic(ROC)curve analysis found that the areas under the curves of serum nesfatin-1, apelin and HO-1 for predicting PDR were 0.842, 0.833 and 0.807 respectively.CONCLUSION:Serum nesfatin-1, apelin and HO-1 levels are closely related to the severity of DR. Dynamic monitoring of serum nesfatin-1, apelin and HO-1 levels is important for the early detection of PDR.

Biological Basis of Five-phase Evolution of Malignant Tumors from Perspective of "Immune Editing" / 中国实验方剂学杂志

Immune escape is one of the ten hallmarks of tumors， which plays an important role in the occurrence and development of tumors. Immune escape refers to a process where tumor cells remodel and edit the immune system through the model of immune clearance， immune balance， and immune escape to "transform" the immune cells into immunosuppressive cells in the tumor microenvironment， so as to support immune escape. The five-stage evolution is the summary of tumor pathogenesis by professor LI Jie. He believes that the gradual development of tumors follows the core pathogenesis of "deficiency-cold-toxin-obstruction-collapse"， in which "depression" runs through the whole process， and cancer toxin is the key. Based on immune editing， this paper combined phenotypic characteristics of tumor cells with the core pathogenesis of the five-stage evolution of professor LI to reveal the biological basis of malignant tumor five-stage evolution. The results indicate that the prominent change from deficiency to cold is the reduction of immune surveillance and the prominent change from toxin to obstruction is immune escape. The final stage of collapse is the outcome of immune failure. Depression is the booster of tumor immune editing. Therefore， the method of reinforcing the healthy Qi and removing toxins was proposed to regulate the immune editing and cut off the five-stage evolution of tumors. Supplementing Qi and warming Yang can reinforce the healthy Qi and restore immune surveillance. Removing toxins and dredging can reverse toxins and immune escape. The harmonizing method can maintain the dynamic balance of immune cells/immunosuppressive cells. Resolving depression can truncate tumor immune editing. Those methods can provide a certain reference for the treatment based on microscopic syndrome differentiation in traditional Chinese medicine （TCM）. In future studies， it is necessary to further explore the specific mechanism of the regulation of immune editing with the methods of supplementing Qi and warming Yang， removing toxins and dredging， their combination， and resolving depression， so as to find out specific Chinese medicines and targets and provide more sufficient evidence for the regulation of tumor immune editing by TCM.

Discriminante analysis of risk factors Nomograms of myopia in children and adolescents in Yunnan Province / 中国学校卫生

Objective@#To explore the related factors of myopia among children and adolescents in Yunnan Province, and to predict and evaluate the influencing factors, so as to provide a scientific theoretical basis for the prevention and control of myopia.@*Methods@#From March 9 to 14, 2023, 848 students from 6 primary and secondary schools in Dali and Lijiang of Yunnan Province were selected by multi stage stratified random cluster sampling method for visual acuity detection and questionnaire survey on myopia related factors. Multivariate Logistic regression analysis was used to establish a Nomogram prediction model for the selected influencing factors.@*Results@#The overall myopia rate of the respondents was 68.3%, the myopia rate of boys (63.4%) was lower than that of girls (72.9%), and the myopia rate of primary school students (46.7%) was lower than that of junior high school students (81.1%), and the difference was statistically significant（ χ 2=8.71, 108.07, P <0.05). Daily eye exercises, activities outside the teaching building during recess, having daily sleep time of 7-9 and >9 h, having both parents without myopia were negatively correlated with the occurrence of myopia in children and adolescents in Yunnan Province ( OR=0.64, 0.63, 0.56, 0.28, 0.48, P < 0.05 ). The reading and writing time after school ≥3 h per day and parents unrestricted time to play video games were positively correlated with myopia ( OR=1.94, 1.78, P <0.05). Based on the influencing factors, a Nomogram prediction model was established to quantitatively evaluate the risk of myopia. The results showed that greater risk for myopia was associated with sleep duration, parental history of myopia, and the time spent reading and writing after school every day.@*Conclusion@#Both genetic factors and environmental factors are related to myopia in children and adolescents. The prediction model of nomogram is beneficial for screening high risk factors of myopia and taking corresponding prevention and treatment measures.

Feasibility of core cervical muscle group exercises and massage in the improvement of cervical spine curvature changes during radiotherapy for head and neck neoplasms / 肿瘤研究与临床

Objective:To investigate the role of cervical core muscle group exercise and massage in the change of cervical spine curvature during radiotherapy for head and neck tumors and the effect on set-up errors.Methods:A total of 40 patients with head and neck tumours receiving radiotherapy in the First Affiliated Hospital of Air Force Military Medical University from March 2020 to July 2021 were prospectively selected, and all of them underwent different degrees of changes in cervical spine curvature during radiotherapy. The cervical core muscle exercise and manual massage were used to do treatment intervention on the change in the cervical spine curvature. Changes in cervical spine curvature at the time of the curvature change of the cervical spine and at 1 d, 3 d and 5 d after the intervention were observed by using cone beam CT, and then data were recorded in 3 dimensions. The set-up error when cervical spine curvature changed was compared with that after the muscle group exercise and manipulation, and Pearson was used to analyze the linear correlation of set-up errors in each direction.Results:There were 23 males and 17 females, with a median age of 41 years (26-62 years). The significant improvement of cervical curvature at 1 d, 3 d and 5 d after the intervention could be found in 2 cases (5.0%), 20 cases (50.0%) and 39 cases (97.5%). Using the cervical 4 vertebrae as the matching standard, the set-up errors at the time of change in cervical spine curvature and at 1 d, 3 d and 5 d after treatment were (1.3±0.9) mm, (1.2±0.8) mm, (1.3±0.7) mm and (1.3±0.7) mm in the left-right direction respectively; (2.0±0.7) mm, (1.7±0.8) mm, (1.8±0.7) mm and (1.9±0.8) mm in the head-foot direction respectively; (4.9±0.7) mm, (4.6±0.7) mm, (3.4±0.7) mm, (1.7±0.6) mm in the anterior-posterior direction respectively. The set-up error in the anterior-posterior directions at 3 d and 5 d after treatment intervention was lower than that at the time of change in cervical spine curvature and at 1 d after treatment intervention (all P < 0.01), and that at 5 d after treatment intervention was lower than that at 3 d after treatment intervention ( P < 0.01). There were no statistically significant differences between the left-right direction and head-foot direction at each time point (all P > 0.05). There was no correlation between left-right direction and head-foot direction ( r = 0.049, P = 0.540), between left-right direction and anterior-posterior direction ( r = 0.041, P = 0.607), and between head-foot direction and anterior-posterior direction ( r = 0.003, P = 0.931) in terms of set-up errors. Conclusions:Core cervical muscle group training and massage could improve the change in cervical spine curvature, increase the repeatability of the set-up, which provides a favourable guarantee for accurate treatment.

Effects of different doses of dexmedetomidine on inflammatory factors and immune function during laparoscopic surgery in patients with gynecological malignant tumors / 肿瘤研究与临床

Objective:To explore the effects of different doses of dexmedetomidine (DEX) on inflammatory factors and immune function in patients with gynecological malignant tumors who underwent laparoscopic surgery.Methods:A total of 60 patients with gynecological malignant tumors who underwent laparoscopic surgery from January 2021 to December 2021 in the Second Hospital of Shanxi Medical University were selected as the research objects. All patients were divided into the control group, low-dose DEX group (group D1) and high-dose DEX group (group D2) by using random number table method, 20 cases in each group. Patients in D1 and D2 groups were intravenously pumped DEX 0.5 μg/kg and 1.0 μg/kg 10 minutes before induction of anesthesia, and then maintained with DEX 0.5 μg·kg -1·h -1 and 1.0 μg·kg -1·h -1 until 30 minutes before the end of operation; and patients in the control group were given the same amount of Nacl solution. The 10 ml peripheral venous blood were collected at 10 minutes before induction of anesthesia (T 1), 1 h after pneumoperitoneum relief (T 2) and 24 h after pneumoperitoneum relief (T 3). The changes of interleukin-6 (IL-6), interleukin-10 (IL-10), the proportion of CD4 +, the proportion of CD8 + and CD4 +/CD8 + ratio of the three groups were compared, and the cases of bradycardia and hypotension in perioperative period and the time of first exhaust after operation were recorded. Results:At T 1,T 2 and T 3, the expression level of IL-6 in the control group was (7.95±0.26) pg/ml, (8.30±0.24) pg/ml and (8.35±0.28) pg/ml, respectively, and the difference was statistically significant ( F = 14.14, P < 0.001); the expression level of IL-10 in the control group was (38.9±2.6) pg/ml, (44.5±6.6) pg/ml and (46.3±4.6) pg/ml, respectively, and the difference was statistically significant ( F = 12.45, P < 0.001); the proportion of CD4 + in the control group was (38.5±2.1)%, (29.5±4.6)% and (29.6±3.5)%, respectively, and the difference was statistically significant ( F = 40.82, P < 0.001); the ratio of CD8 + in the control group was (30.1±3.7)%, (35.1±6.3)% and (40.3±8.2)%, respectively, and the difference was statistically significant ( F = 13.02, P < 0.001); the CD4 +/CD8 + ratio in the control group was 1.29±0.14, 0.84±0.09 and 0.75±0.14, respectively, and the difference was statistically significant ( F = 99.94, P < 0.001). The expression level of IL-6 in group D1 and group D2 was (8.10±0.32) pg/ml and (8.01±0.30) pg/ml at T 2, and (8.12±0.35) pg/ml and (8.05±0.34) pg/ml at T 3,which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The expression level of IL-10 in group D2 was (40.6±3.5) pg/ml at T 2, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the expression level of IL-10 in group D1 and group D2 was (43.7±3.5) pg/ml and (42.4±3.9) pg/ml, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD4 + in group D2 was (34.5±4.3)%, which was higher than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD4 + in group D1 and group D2 was (32.1±4.2)% and (33.7±2.8)%, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD8 + in group D2 was (30.7±5.5)%, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD8 + in group D1 and group D2 was (35.4±5.8)% and (32.5±5.1)%, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The CD4 +/CD8 + ratio in group D1 and D2 was 0.99±0.17 and 1.14±0.16 at T 2, 0.93±0.19 and 1.05±0.16 at T 3, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). Meanwhile, 1 case of hypotension occurred in the the control group and group D1, respectively; 3 cases of bradycardia and 2 cases of hypotension occurred in the group D2. The time of exhaust in the control group was later than that in group D1 and D2, and the difference was statistically significant ( P < 0.05). Conclusions:DEX can inhibit the inflammatory reaction during laparoscopic surgery in patients with gynecological malignant tumors, reduce immune damage. The anti-inflammatory action and immune protection of high-dose of DEX is more significant compared with low-dose of DEX, while high dose of DEX is more likely to cause hemodynamic fluctuations in perioperative period.

Ethical review and management of serious adverse events in anti-tumor drug clinical trials / 中华医学科研管理杂志

Objective:To discuss ethical review and management of serious adverse events in anti-tumor drug clinical trials in a grade A tertiary cancer hospital for timely and effective protection of subjects.Methods:The main contents and ethical management of ethical review on serious adverse events were retrospectively analyzed including the number, distribution rules, and whether they were reported in time in clinical trials conducted in our hospital in 2021.Results:A total of 1 789 serious adverse events in 259 clinical trials were reported, with more male subjects than female, with an average age of 59.95 years, mainly concentrated in the 50~59 age and 60~69 age groups, accounting for 27.45% and 42.37% respectively. Digestive oncology department, thoracic oncology department and renal cancer melanoma department ranked in the top three for the number of clinical trials and reports of serious adverse events. The highest incidence of serious adverse events was hospitalization at 63.44% and the lowest incidence was disability at 0.39%. The highest proportion of serious adverse events possibly related to clinical trials was 35.72%. Expected serious adverse events accounted for 65.85% versus 34.15% unexpected ones, and the difference between different correlations of serious adverse events whether they were expected or not.was statistically significant. Among the measures taken by the investigator for the test drugs due to serious adverse events, drug discontinuation was the most, accounting for 42.54%, while 3.07% of the trial plans modified the study protocol/informed consent. Serious adverse events reported within 24 hours accounted for 87.20%, and those reported in 24 hours and beyond accounting for 12.80%. A statistically significant difference of the reporting time between the registered and investigator initiated clinical trials was observed.Conclusions:The ethics committee should attach importance to ethical review and management of serious adverse events, pay attention to whether they were reported timely and accurately, strengthen supervision, and effectively protect the safety and interests of the subjects.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Isolated ocular colobomas caused by a novel variant of the YAP1 gene / 中华眼底病杂志

Objective:To identify the causative gene and observe the phenotypic characteristics of a family with isolated microphthalmia-anophthalmia-coloboma (MAC).Methods:A retrospective clinical study. One patient (proband) and 3 family members of a family with MAC visited the Henan Eye Hospital from May 2019 to May 2022 were included in the study. The patient's medical history and family history were inquired in detail, and the best corrected visual acuity (BCVA), slit lamp microscope, fundus photography, optical coherence tomography (OCT), ophthalmological B mode ultrasound and axial length (AL) measurement were performed. The peripheral venous blood of the proband, his parents and brother was collected for Trio whole-exome sequencing and pathogenic gene screening. Fluorescence quantitative Polymerase chain reaction was used to verify the suspicious variations. The clinical features of the patient's ocular and systemic also were observed.Results:The proband, male, was 3 years old at the first visit. The horizontal pendular nystagmus was detected in both eyes. Vertical elliptical microcornea and keyhole-shaped iris colobomas were detected in both eyes. The objective refraction at first visit (3 years old) was -4.00 DS/-0.50 DC×105° (OD) and -3.50 DS/-1.25 DC×80° (OS). Refraction and BCVA at 6 years old: -6.50 DS/-2.00 DC×110°→0.05 (OD) and -6.00 DS/-1.50 DC×80°→0.2 (OS). The AL at 4 years and 10 months old was 24.62 mm (OD) and 23.92 mm (OS), respectively. The AL at 5 years and 7 months old was 25.24 mm (OD) and 24.36 mm (OS), respectively. Ultrasonography shows tissue defects in both eyes. Fundus photography showed the inferior choroidal coloboma involving optic disc. OCT showed the optic disc in both eyes was abnormal with colobomas around, and the retinal neurosensory layer in colobomas area was disordered and thin; the retinoschisis was visible in the left eye. The proband's parents and siblings have normal phenotypes. Whole exome sequencing reveals a denovo heterozygous deletion of YAP1 gene: YAP1, chr11: 10280247-102100671, NM_ 001130145, loss 1 (EXON: 6-9). The results of bioinformatics analysis were pathogenic variants. Parents and siblings were of the wild type. Conclusions:Loss of heterozygosity in exons 6-9 of YAP1 gene is the pathogenic variation in this family. It can cause abnormal development of anterior segment, chorioretinal colobomas, deepening of axial myopia, even severe macular colobomas and retinoschisis.