Iodine nutritional status is not a direct factor in the prevalence of the BRAFV600E mutation in papillary thyroid cancer

ABSTRACT Objectives: Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. Of the iodine-metabolizing genes, BRAFV600E is a highly specific target for PTC and may have a reciprocal causative relationship with iodide-metabolizing genes. Materials and methods: In this study, we performed a data analysis of selected quantitative studies to determine the relationship between iodine nutritional status and the prevalence of the BRAF600E mutation in patients with PTC. Five studies were selected for meta-analysis based on the selection criteria. Results: A total of 2,068 patients were divided into three groups: low (urinary iodine concentration [UIC] < 100 μg/L), adequate (UIC 100-200 μg/L), and high (UIC ≥ 200 μg/L). The results were obtained using RevMan software, and the pooled odds ratios (ORs) were calculated using Mantel-Haenszel statistics with a 95% confidence interval (CI). The OR for the prevalence of the BRAFV600E mutation between the high and adequate groups was 1.25 (95% CI 0.64-2.43, p = 0.51), and the OR between the low and adequate groups was 0.98 (95% CI 0.42-2.31, p = 0.96). The BRAFV600E mutation risk did not change significantly at different levels of iodine nutrition (p = 0.33) in statistical analyses. Conclusion: We conducted preliminary research on dietary iodine intake and the BRAFV600E mutation in PTC. The results suggested that abnormal iodine intake might not directly influence the prevalence of the BRAFV600E mutation in these patients. Further research into the associations between dietary iodine intake and the BRAFV600E mutation in PTC, including the underlying mechanisms, is required.

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.

Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway / 中国结合医学杂志

OBJECTIVE@#To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms.@*METHODS@#MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%, 20% and 40%) groups, GZFLC (10%, 20%, and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved caspase-3, -9, cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC (840, 420, or 210 mg/kg per day, respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry.@*RESULTS@#GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential (P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3, -9, Cytc and Apaf-1 were increased (all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (P<0.05).@*CONCLUSION@#GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.

Clinicopathological characteristics and prognosis of non-Hodgkin lymphoma in oral and maxillofacial regions: An analysis of 369 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions.@*METHODS@#Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively.@*RESULTS@#There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients.@*CONCLUSION@#Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.

Recent progress in the treatment of intractable sialolithiasis / 北京大学学报(医学版)

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.

The role of the national oral health program in the development of oral health service and related thinkings / 中华口腔医学杂志

Conception of public health was firstly put forward by American professor Winslow. Ensuring and promoting the health of general population is the key connotation for the definition of public health. Oral disease has become a public health problem. Caries which preventable and curable is the most common oral disease and the etiology is also clear. Oral health comprehensive intervention program for children in central and western regions was set up in 2008 by Chinese government. The program included sealing on the first permanent molar and oral health education towards primary school children covering mid-west area. This was the first oral health program invested by government and managed by Chinese Stomatological Association. Six years later, the program was popularized to the whole nation, and renamed as national oral health comprehensive intervention program for children in China. The program had made deep impact on development of oral health service in China. The study tries to analyze the challenges of oral health service through reviewing the background, content, organization and effectiveness of the program, aiming to provide suggestions on policy, financing, system, ability and technology for the future development.

Research progress on cirrhosis reversal and recompensation / 中华肝脏病杂志

Previously, liver lesions in cirrhosis were considered irreversible, especially because the condition aggravated gradually after entering the decompensated phase, thus making it difficult to return to the compensated phase. At present, more and more evidence shows that some patients with decompensated liver cirrhosis can be recompensated after the cause is controlled and complications are managed. This article explores the research progress related to LC reversal and recompensation from three aspects: liver histopathology, liver function, and clinical complications.

Three cases of occupational acute trimethyltin chloride poisoning / 中华劳动卫生职业病杂志

Trimethyltin chloride is a highly toxic substance, which is absorbed through respiratory tract, skin and digestive tract, with central nervous system injury as the main clinical manifestations, and can be accompanied by damage to various organs. In this paper, the treatment process of 3 patients with acute trimethyltin chloride poisoning was reviewed, and their clinical manifestations, auxiliary examination, diagnosis and treatment were analyzed. Three patients were misdiagnosed as mental abnormality, encephalitis, and hepatic encephalopathy in different hospitals in the early stage of medical treatment, suggesting that clinicians should pay attention to the occupational contact history of poisoned patients and conduct toxicant detection in time to avoid misdiagnosis and mistreatment.

Rapid determination of acetaminophen in plasma by LC-MS/MS / 中华劳动卫生职业病杂志

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML).@*METHODS@#A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m2·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety.@*RESULTS@#There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05).@*CONCLUSIONS@#Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.

Platelet-to-lymphocyte ratio as a biomarker for predicting coronary artery lesions in Chinese children with Kawasaki disease: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD).@*METHODS@#A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1.@*RESULTS@#A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001).@*CONCLUSIONS@#PLR demonstrates certain predictive value for CAL in Chinese children with KD.

Research progress in pharmacological effects and chemical components of processed Angelicae Sinensis Radix products / 中国中药杂志

Angelicae Sinensis Radix is one of the main Chinese medicinal materials with both medicinal and edible values. It has the functions of tonifying and activating blood, regulating menstruation and relieving pain, and moistening intestines to relieve constipation. It is mainly produced in the southeastern Gansu province, and that produced in Minxian, Gansu is praised for the best quality. The chemical components of Angelicae Sinensis Radix mainly include volatile oils, organic acids, and polysaccharides, which have anti-inflammatory, pain-relieving, anti-tumor, anti-oxidation, immunomodulatory and other pharmacological effects. Therefore, this medicinal material is widely used in clinical practice. By reviewing the relevant literature, this study systematically introduced the research status about the chemical constituents and pharmacological effects of processed Angelicae Sinensis Radix products, aiming to provide a theoretical reference and support for the future research, development, and clinical application of related drugs.

Newly developed gas-assisted sonodynamic therapy in cancer treatment

Sonodynamic therapy (SDT) is an emerging noninvasive treatment modality that utilizes low-frequency and low-intensity ultrasound (US) to trigger sensitizers to kill tumor cells with reactive oxygen species (ROS). Although SDT has attracted much attention for its properties including high tumor specificity and deep tissue penetration, its anticancer efficacy is still far from satisfactory. As a result, new strategies such as gas-assisted therapy have been proposed to further promote the effectiveness of SDT. In this review, the mechanisms of SDT and gas-assisted SDT are first summarized. Then, the applications of gas-assisted SDT for cancer therapy are introduced and categorized by gas types. Next, therapeutic systems for SDT that can realize real-time imaging are further presented. Finally, the challenges and perspectives of gas-assisted SDT for future clinical applications are discussed.

Frailty evaluation and risk factors for older patients with comorbidities: a cross-sectional study / 中华老年医学杂志

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Establishment of prediction nomogram model of type 2 diabetes mellitus complications based on laboratory indexes such as glycosylated hemoglobin / 中国医师进修杂志

Objective:To study the effect of related laboratory indexes such as glycosylated hemoglobin on the occurrence of complications in patients with type 2 diabetes mellitus, and to construct a nomogram model.Methods:The clinical data of 203 patients with 2 diabetes mellitus from May 2020 to April 2022 in Quzhou Hospital, Zhejiang Medical and Health Group were retrospectively analyzed. Among them, 64 patients had no diabetic complications (control group), and 139 patients had diabetic complications (complication group). The clinical data of the two groups were recorded, and the related influencing factors of complications in patients with type 2 diabetes were analyzed; receiver operating characteristic (ROC) curve was used to analyze the predicting value of significant indexes for the complications in patients with type 2 diabetes; multivariate Logistic regression analysis was used to analyze the independent risk factors of complications in patients with type 2 diabetes; R language software 4.0 "rms" package was used to construct the nomogram model for predicting the complications in patients with type 2 diabetes, the calibration curve was internally validated, and the decision curve was used to evaluate the predictive efficacy of the nomogram model.Results:The hypertension rate, hyperlipemia rate, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin in complication group were significantly higher in those in control group: 44.60% (62/139) vs. 20.31% (13/64), 48.92% (68/139) vs. 25.00% (16/64), (5.42 ± 0.68) years vs. (4.84 ± 0.51) years, (12.60 ± 2.80) mmol/L vs. (10.20 ± 1.90) mmol/L, (16.50 ± 3.10) mmol/L vs. (12.50 ± 2.90) mmol/L and (9.62 ± 1.33)% vs. (7.96 ± 0.85)%, and there were statistical differences ( P<0.01); there were no statistical differences in gender composition, age, body mass index, smoking rate, drinking rate, albumin and creatinine between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of the course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin for predicting the complications in patients with type 2 diabetes were 0.725, 0.752, 0.830 and 0.861, respectively; the optimal cut-off values were 5 year, 11.8 mmol/L, 15.1 mmol/L and 9.23%. Multivariate Logistic regression analysis result showed that hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin were independent risk factors of complications in patients with type 2 diabetes ( OR = 1.563, 1.692, 1.451, 1.703, 1.506 and 1.805; 95% CI 1.268 to 1.689, 1.483 to 1.824, 1.215 to 1.620, 1.402 to 1.903, 1.303 to 1.801 and 1.697 to 1.926; P<0.05). The hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin were used as predictors to construct a nomogram model for predicting the complications in patients with type 2 diabetes. Internal validation result showed that the nomogram model predicted the complications with good concordance in patients with type 2 diabetes (C-index = 0.815, 95% CI 0.796 to 0.843); the nomogram model predicted the complications in patients with type 2 diabetes at a threshold >0.18, provided a net clinical benefit, and all had higher clinical net benefits than hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin. Conclusions:The nomogram model constructed based on hypertension, hyperlipemia, course of disease, fasting blood glucose, postprandial 2 h blood glucose and glycosylated hemoglobin has better clinical value in predicting the complications in patients with type 2 diabetes.

Molecular mechanism of microRNAs regulating sorafenib resistance in hepatocellular carcinoma / 中国药理学通报

Hepatocellular carcinoma (HCC) is one of the most deadly malignancies in the world, with strong invasiveness, low cure rate, high metastasis rate and poor prognosis. Sorafenib is the most important and effective first-line drug for the treatment of advanced hepatocellular carcinoma, but its clinical efficacy is severely limited by primary and acquired drug resistance. Mi-crornas ( micrornas) are small non-coding Rnas that play a key regulatory role in the occurrence and development of hepatocellular carcinoma and the progression of sorafenib resistance. This paper summarizes the role of micrornas in the initiation and development of sorafenib resistance in hepatocellular carcinoma, in order to further understand the mechanism of sorafenib anti-hep-atocellular carcinoma, and to provide valuable theoretical basis for clinical targeted therapy and prognosis improvement in hepatocellular carcinoma.

Role and possible mechanism of estrogen receptor α down-regulation leading to damage of TM4 Sertoli cell connectivity in mice / 中国药理学通报

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress / 中国药理学通报

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.