[Stratified endocrine therapy for advanced breast cancer: stratification guided, combination preferred].

The endocrine therapy of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer has stepped into an era of targeted combination therapy. Many targeted agents, led by cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), have provided abundant treatment options for patients with HR-positive HER2-negative advanced breast cancer. To meet the needs of clinical practice in China and standardize the administration of targeted agents, the stratified endocrine strategy for advanced breast cancer has been proposed by Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines based on medicine evidence and drug accessibility, offering scientific and organized decision-making guidance for clinical oncologists.

[Serum immunoglobulin concentration and the risk of type 2 diabetes mellitus in adults in Tianjin City: a prospective cohort study].

Objective: To evaluate the association between immunoglobulin concentration and the risk of type 2 diabetes mellitus (T2DM) in adults in Tianjin City. Methods: Based on the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort from January 2010 to December 2018, subjects who had completed the measurement of baseline immunoglobulin concentration and blood glucose concentration and not been diagnosed with any type of diabetes at baseline were selected in this study. The collected data included the concentration of serum immunoglobulin (IgG, IgM, IgA and IgE), fasting blood glucose and other potential confounders. The subjects were divided into four groups from Q1 to Q4 according to the quartiles of baseline immunoglobulin concentration. The multivariable Cox regression model was used to assess the association between the baseline immunoglobulin concentration and T2DM. Results: A total of 6 315 subjects aged (50.1±10.0) years were included. About 390 subjects were newly diagnosed with T2DM during the follow-up period. The incidence rate was 16.8/1 000 person-years. After adjusting for age, sex, waist circumference, smoking status, drinking status, eosinophil ratio, metabolic syndrome, first-or second-degree family history, and reciprocal adjusting for other immunoglobulin concentrations, compared to the lowest quartile concentration group Q1, subjects in group Q4 with the highest quartile of IgG concentration showed a lower risk of T2DM (HR=0.71, 95%CI: 0.52-0.97), and subjects in group Q4 with the highest quartile of IgM concentration also had a decreased risk of T2DM (HR=0.66, 95%CI: 0.47-0.91). Subjects in group Q4 with the highest quartile of IgA concentration had an increased risk of T2DM (HR=1.56, 95%CI: 1.18-2.07). The risk of T2DM decreased with the increase of serum IgG and IgM concentrations (Ptrend=0.018, Ptrend=0.010) and increased with the increase of serum IgA concentrations (Ptrend<0.001). No association was found between the concentration of IgE and T2DM risk (HR=0.99, 95%CI: 0.74-1.31, Ptrend=0.891). Conclusion: The concentration of IgG and IgM is negatively associated with the risk of T2DM, and the concentration of IgA is positively associated with the risk of T2DM in Tianjin City. The concentrations of IgG, IgM and IgA could be a predictor of hyperglycemia and T2DM.

[A deep learning segmentation model for detecting caries in molar teeth].

This study aimed to build a home use deep learning segmentation model to identify the scope of caries lesions. A total of 494 caries photographs of molars and premolars collected via endoscopy were selected. Subsequently, these photographs were labeled by physicians and underwent segmentation training by using DeepLabv3+, and then verification and evaluation were performed. The mean accuracy was 0.993, the sensitivity was 0.661, the specificity was 0.997, the Dice coefficient was 0.685, and the intersection over union (IoU) was 0.529. Therefore, the present deep learning segmentation model can identify and segment the scope of caries.

[Evaluation of the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province-based on interrupted time series].

Objective: To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province. Methods: Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design. Results: The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 (t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 (t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 (ß1+ß3=0.071). Conclusions: The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

Prolymphangiogenic Effects of 9-cis Retinoic Acid Are Enhanced at Sites of Lymphatic Injury and Dependent on Treatment Duration in Experimental Postsurgical Lymphedema.

Background: Patients undergoing surgical treatment for solid tumors are at risk for development of secondary lymphedema due to intraoperative lymphatic vessel injury. The damaged lymphatic vessels fail to adequately regenerate and lymphatic obstruction leads to fluid and protein accumulation in the interstitial space and chronic lymphedema develops as a result. There are currently no effective pharmacological agents that reduce the risk of developing lymphedema or treat pre-existing lymphedema, and management is largely palliative. The present study investigated the efficacy of various 9-cis retinoic acid (9-cis RA) dosing strategies in reducing postsurgical lymphedema by utilizing a well-established mouse tail lymphedema model. Methods and Results: Short-duration treatment with 9-cis RA did not demonstrate a significant reduction in postoperative tail volume, nor an improvement in lymphatic clearance. However, long-term treatment with 9-cis RA resulted in decreased overall tail volume, dermal thickness, and epidermal thickness, with an associated increase in functional lymphatic clearance and lymphatic vessel density, assessed by LYVE-1 immunostaining, compared with control. These effects were seen at the site of lymphatic injury, with no significant changes observed in uninjured sites such as ear skin and the diaphragm. Conclusions: Given the reported results indicating that 9-cis RA is a potent promoter of lymphangiogenesis and improved lymphatic clearance at sites of lymphatic injury, investigation of postoperative 9-cis RA administration to patients at high risk of developing lymphedema may demonstrate positive efficacy and reduced rates of postsurgical lymphedema.

[Orexin-A inhibits γ-aminobutyric acid current of neonatal rat spinal cord ventral horn neurons by activating OX1R, OX2R and Ca2+-independent PKC].

OBJECTIVE: To investigate the effect of orexin-A on the functionality of ionotropic γ-aminobutyric acid (GABA) receptors in spinal cord ventral horn neurons and its mechanisms. OBJECTIVE: The spinal cord containing the lumbosacral enlargement was isolated from neonatal SD rats (7-12 days old) and sliced. The slices were digested with papain (in 0.18 g/30 mL artificial cerebrospinal fluid) for 40-60 min, and the ventral horn neurons were separated acutely using fire-polished Pasteur pipettes. After the cells adhered to the bottom of Petri dishes, patch-clamp experiments combined with pharmacological methods were performed to test the effects of orexin-A on GABA currents of the neurons treated with SB334867 (a selective OX1R antagonist), TCSOX229 (a selective OX2R antagonist), Bis-Ⅳ (a PKC inhibitor), PMA (a PKC agonist), Rp-cAMP (a PKA inhibitor), or BAPTA (Ca2+ chelator). OBJECTIVE: The isolated neurons maintained good morphologies with diverse shapes of cell body and long protrusions. Treatment with orexin-A significantly inhibited the amplitude of GABA-induced current (P < 0.001, n=49) with an inhibition rate of (67.48±12.50)%. SB334867 and TCSOX229, when applied simultaneously, completely abolished the suppressive effect of orexin-A on the GABA currents (P=0.93, n=6), and their separate use partially relieved the suppressive effect of orexin-A (P=0.001, n=8; P=0.02, n=8). The application of Bis-Ⅳ also abolished the suppressive effect of orexin-A on GABA currents (P=0.31, n=5). PMA mimicked the effect of orexin-A in these neurons and significantly inhibited GABA currents with an inhibition rate of (60.79±10.94)%, and the application of orexin-A did not cause further suppression of GABA currents in PMA-treated neurons (P=0.15, n=6). Orexin-A was still capable of suppressing GABA currents in Rp-cAMP-treated neurons (P=0.001, n=5). The extracellular Ca2+-free solution (P=0.004, n=8) or the presence of BAPTA (P=0.04, n=7) did not significantly affect the inhibitory effect of orexin-A on GABA currents. OBJECTIVE: Orexin-A inhibits GABA currents in the ventral horn neurons of rat spinal cord probably by activating OX1R, OX2R and Ca2+-independent PKC.

Antitumor effects of apoptin expressed by the dual cancer-specific oncolytic adenovirus - a review.

Apoptin is a small molecular weight protein derived from chicken anemia virus, which can induce the apoptosis of transformed cells and tumor cells and leave primary and nontransformed cells unharmed. Apoptin's cell localization depends on its own phosphorylation state and cell type. In tumor cells, phosphorylated apoptin enters the nucleus and induces apoptosis. While, in normal cells apoptin mainly exists in the cytoplasm. Apoptin, as a disordered protein in cells, interacts with many proteins in cell signal pathways to induce apoptosis of tumor cells. The specific mechanism of apoptosis induced by apoptin has not been completely elucidated. Therefore, apoptin has become a potential anticancer agent. This review summarizes the research results of apoptin in our laboratory and reveals the specific antitumor mechanism of apoptin expressed by oncolytic virus vector on a variety of tumor cells and mouse models.

STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

Correction: Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity.

Following publication of this Article the Authors noted that a blot in Fig. 1c was misplaced and images were inadvertently duplicated in Supplementary Fig. S2 and Fig. S3. The corrected Fig.1 can be found below. The incorrect Supplementary files have been replaced online. The scientific conclusions of this paper were not affected.

[Investigation on social security of pneumoconiosis patients in Chongqing].

Objective: To investigate the living conditions, insurance coverage, and assistance of pneumoconiosis patients diagnosed in Chongqing from May 2006 to May 2018. Methods: A cross-sectional survey was conducted in July 2018, and 40 890 pneumoconiosis patients from occupational diseases report management agency were obtained. 34 625 cases meeting the inclusion criteria were investigated, and descriptive statistical analysis was performed on the data. Results: There were 34 625 cases of pneumoconiosis patients alive in Chongqing, and 22730 (65.6%) had participated in work-related injury insurance, 6 308 (18.2%) had participated in basic medical insurance for urban employees which were still effective. 27 056 (78.1%) had participated in cooperative insurance for urban and rural residents which were still effective. 4 393 (12.7%) received assistance for the residents in need in urban and rural areas. 5827 (16.8%) benefited the policy of "Xiangyu Railway". There were 7 961 cases (2.4%) whose work-related injury insurance had expired did not get one-off compensation, and did not receive any assistance. Conclusion: Most of the patients with pneumoconiosis in Chongqing obtained protection in terms of work-related injury insurance, medical insurance, civil assistance and poverty alleviation to a certain extent, but the strength of the guarantee is not enough. Patients with pneumoconiosis might suffer from poverty caused by illness. It is recommended to improve the system of work-related injury insurance benefits, establish special funds for pneumoconiosis patients, strengthen health education and health promotion for pneumoconiosis patients, and strengthen the management of pneumoconiosis patients.

[Epidemiological analysis of new pneumoconiosis among workers in coal industry in Chongqing].

Objective: To analyze the incidence of pneumoconiosis among workers in the coal industry in the past 13 years in Chongqing, understand the different epidemiological characteristics of new pneumoconiosis among workers in the coal industry in the city, provide basic evidence for the prevention and treatment of pneumoconiosis. Methods: Collecting new cases of pneumoconiosis diagnosed in the coal industry in Chongqing in January 2006-May 2018, and analyze its epidemiological characteristics. Results: In January 2006-May 2018, 25329 cases of pneumoconiosis were added to workers in the coal industry in Chongqing, and 23, 328 cases were present, all male. Among the existing cases: coal workers' pneumoconiosis accounted for 89.30%, silicosis accounted for 10.70%; age distribution was 50-59 years old. The main, accounting for 45.19%, the average age of onset was 52.21±7.45 years; the actual dusting age was mainly 10-19 years, the average actual working age was 17.52±8.47 years; the distribution of the work was mainly by the main coal mining (53.20%) ; There are more new cases in enterprises, accounting for 88.86%; distributed in 36 districts and counties. Conclusion: There was a large number of new pneumoconiosis diseases in the coal industry in Chongqing. Different measures should be taken according to the characteristics of different enterprises, and relevant enterprises should be urged to take the initiative to carry out occupational health surveillance, effectively protect the health of workers, improve the coordination mechanism, improve medical security, and gradually realize government assistance and Social care is combined.

[Study on clinical classification of Japanese encephalitis by Bayes discriminant analysis].

Objective: To construct Bayes discriminant function for clinical classification of common and severe Japanese encephalitis (JE) cases, and to identify cases accurately with quantitative indicators. Methods: Samples of confirmed common and severe JE cases reported by the epidemic surveillance system of Gansu Provincial Center for Disease Control and Prevention from 2005 to 2017 were collected. Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis were used to screen meaningful clinical indicators, so as to construct and evaluate Bayes discriminant function. Results: There were 256 common JE cases and 257 severe JE cases. There were no significant differences in sex, age and occupation distributions between the two groups (P>0.05) and there was significant difference in case fatality rate (P<0.05). Non-conditional logistic regression analysis and Bayes stepwise discriminant analysis, combined with using related literature, to screen 11 clinical indicators for the construction of Bayes discriminant function. Interactive validation showed that the sensitivity of discriminant function was 71.48% (95%CI: 65.53%-76.93%) and the specificity was 73.93% (95%CI: 68.11%-79.19%). The area under ROC curve was 0.761 (95%CI: 0.720-0.803) and the total accuracy rate was 72.71%. Conclusion: Bayes discriminant function can be used to identify common and severe JE cases more accurately, which is helpful for the reasonable treatment and good prognosis of JE patients.

The detection of porcine circovirus 3 in Guangxi, China.

Porcine circovirus type 3 (PCV3) is a novel circovirus that was firstly detected in the USA. PCV3 is associated with porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure and cardiac and multisystemic inflammation. Latterly, PCV3 was detected in Guangxi, China. Forty-one of 108 (37.96%) samples and nine of 47 (19.14%) samples were PCV3 positive in pig farms and pig slaughter houses, respectively. Three PCV3 strains were sequenced and designated PCV3-China/GX2016-1, PCV3-China/GX2016-2 and PCV3-China/GX2016-3. The complete genome of PCV3-China/GX2016-2 and PCV3-China/GX2016-3 is both 2,000 bp in length, while PCV3-China/GX2016-1 is of 1,999 bp and has a G deletion at position of 1,155 in its genome. The complete genome and capsid nucleotide of the three PCV3 strains identified in this study shared 97.5%-99.4% and 96.7%-99.1% identities with that of the other PCV3 strains available in NCBI, respectively. Phylogenetic analysis based on complete genome and capsid gene of 35 PCV3 strains showed that the three PCV3 sequences from Guangxi Province were divided into two clusters. The results of this study contribute to the understanding of PCV3 molecular epidemiology.

[Clinical characteristics of 128 hospitalized patients with syndrome of inappropriate antidiuretics of different etiologies].

Objective: To summarize and analyze the clinical features and etiologies in hospitalized patients with syndrome of inappropriate antidiuretics (SIAD) during the past 25 years. Methods: All data of 128 patients with SIAD admitted to Chinese PLA General Hospital since January 1991 to January 2016 were collected. SIAD was diagnosed based on the 1957 criterion. Results: (1) The most frequent causes of increased inappropriate secretion of vasopressin were malignant tumors, lung diseases (e. g. pneumonia), and central nervous system diseases, in which malignant tumors accounted for 38.28% of the SIAD. (2) During the past 25 years, the proportion of malignant diseases declined from 4/7 to 35.29%, while, the proportion of pulmonary infection increased from 1/7 to 35.29% (P<0.05). (3) The patients with malignant tumors had the lowest serum sodium and serum osmolality among all SIAD patients. (4) CT scan had a high diagnostic value for chest and brain detection. (5) Among three SIAD subjects with unknown reasons at onset, two were diagnosed with small cell lung cancer and one with gastric cancer during follow-up. Conclusion: The etiology of SIAD is complex and it could be attributed to multifarious etiological factors. Malignant tumors account for the largest proportion of all patients, and pulmonary infection was ranked in second place. Cautions on tumors have to be taken when serum sodium of a SIAD patient is below 118.1 mmol/L.

[An analysis of four cases of misdiagnosed primary lymphocytic hypophysitis].

To improve the differential diagnosis of sellar region mass, 4 cases with sellar mass and misdiagnosed as lymphocytic hypophysitis (LYH) were reviewed retrospectively.The 4 patients (2 male and 2 female) aged 20-60 years old were all presented with symptoms of headache, polydipsia and polyuria.Biochemical studies confirmed the diagnoses of central diabetes insipidus and hypopituitarism.Head MRI scans showed LYH like image for all the cases, and, thus, high dose methylprednisolone pulse therapy (HDMPT) was applied to the patients.Their symptoms deteriorated and the sellar mass enlarged after a short period of partial improvement.Operations were performed in all the patients.Histology study showed craniopharyngioma with abscess, primary abscess, secondary hypophysitis caused by Wegener's granulomatosis, and germinoma with secondary hypophysitis, respectively.In conclusion, surgery or biopsy is necessary for those who presented with sellar region mass and was suspected to be with LYH, but with poor response or even worse after HDMPT.

Serological investigation of Mycoplasma synoviae infection in China from 2010 to 2015.

Mycoplasma synoviae can cause worldwide respiratory diseases, synovitis, or subclinical symptoms in poultry. M. synoviae infection occurs throughout the yr and causes significant economic losses, including increased mortality, condemnations, medication, and live production cost. In the present study, the seroprevalence of M. synoviae among 44,395 non-vaccinated chickens from 21 provinces in China from 2010 to 2015 was estimated using ELISA. The overall seroprevalence was 41.19%. Seropositive rates in different yr ranged between 24.70 and 57.20%; the highest seropositive rate was observed in 2010, and the lowest was observed in 2013. The prevalence rates varied greatly in different provinces from 5.10 to 100%. Of the 463 commercial flocks tested, 375 (80.99%) were positive for M. synoviae by ELISA. The seasonal distribution ranged between 26.83% (in October) and 53.98% (in July). An investigation of chickens according to age further showed that M. synoviae can infect chickens at any age. Our findings indicate that M. synoviae infection is very common in China and should prompt further research into its prevalence to develop effective control and prevention strategies.

Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.

Apigenin is an important flavonoids due to its antidiabetic bioactivity. It was reported experimentally that the 7-substituent derivative of apigenin has higher biological activity than 4'- and 5-substituted derivatives while introducing sole carboxyalkyl group -(CH2)7COOH into the parent structure. Molecular docking studies indicated that the other two derivatives have lower binding affinities than the 7-substituent derivative (-7.52 kcal mol-1), which is considered to be a better inhibitor than the parent molecule. Almost all of the carbon atoms and oxygen atoms are coplaner for all three molecules in solution phase, however, all carboxyalkyl groups bend inside into the parent molecules in the active site, and the jagged geometries of the carbon chains are destroyed correspondingly. In addition, most of the electron densities of the chemical bonds for all molecules are decreased, especially the 7-substituent derivative. In contrast, most of the Laplacian values for three molecules are increased in the active site, which suggests that the charge densities at the bond critical point (bcp) are much more depleted than the solution phase. Dipole moments of derivatives are all increased in the active site, suggesting strong intermolecular interactions. After interacting with the S. cerevisiae α-glucosidase, only the 7-substituent derivative has the lowest energy gap ΔE HOMO-LUMO, which indicates the lowest stability and the highest inhibition activity. Graphical abstract Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.

Comparison of the molecular interactions of 7'-carboxyalkyl apigenin derivatives with S. cerevisiae α-glucosidase.

As one of the most investigated flavonoids, apigenin, is considered to be a strong α-glucosidase inhibitor. However, the clinical utility of apigenin is limited due to its low solubility. It was reported that the solubility and biological activity can be improved by introducing sole carboxyalkyl group into apigenin, especially the 7'-substitution. With the increase of length of the alkyl chain in carboxyalkyl group, B ring of the apigenin derivative is embedded much more deeply into the binding cavity while the carboxyalkyl stretches to the neighboring cavity. All of the terminal carboxyl groups form hydrogen bonding interactions easily with the surrounding polar amino acids, such as His239, Ser244, Arg312 and Asp349. Thus, the electron density values of the carbonyl in the carboxyl group become higher than the solution status due to the strong molecular interactions. In fact, electron densities of most of the chemical bonds are decreased after molecular docking procedure. On compared with the solution phase, however, dipole moments of most of these molecules are increased, and their vectors are reoriented distinctly in the active sites. It is noticed that all of the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are distributed throughout the whole parent apigenin ring in solution phase, whereas the disappeared situation happened on the B rings of some molecules (II-IV) in the active site, leading to higher energy gaps.