A highly distorted ultraelastic chemically complex Elinvar alloy.

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.

Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

[Evaluation of brain age changes in patients with liver cirrhosis and hepatic encephalopathy with deep learning models based on structural magnetic resonance imaging].

Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

[Annual progress of immunotherapy for tuberculosis in 2023].

As a chronic infectious disease, tuberculosis (TB) is closely related to immune regulation and immune effect. Immunotherapy which can improve the curative effect of tuberculosis and control the spread of tuberculosis, is one of the important means for the comprehensive treatment of tuberculosis. From October 2022 to September 2023, research on the immunotherapy of tuberculosis at home and abroad continues to increase, providing new opportunities for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. Host-targeted therapy and therapeutic vaccines are new directions for research into TB adjuvant therapy.

Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography.

Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.

[Analysis of vaginal microecology in 23 181 cases of the gynecological female outpatients].

Objective: To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients. Methods: A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed. Results: (1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P<0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P>0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions: Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

[Mechanism of piRNA in bisphenol A-promoted invasion and migration of prostate cancer cells].

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC20) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 µmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.

[Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma].

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34ßE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34ßE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice.

Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gram-negative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/PFKFB3/NF-κB inflammatory pathway.

Does mental health mediate the effect of deviant peer affiliation on school adaptation in migrant children: evidence from a nationally representative survey in China.

OBJECTIVES: This study aimed to examine the impact of deviant peer affiliation on migrant children's school adaptation in China and explore the mediating role of mental health in the relationship between deviant peer affiliation and school adaptation among migrant children. STUDY DESIGN: This was a cross-sectional study based on secondary data. METHODS: This study was based on the nationally representative China Education Panel Survey. Multiple linear regression models were used to quantify the relationship between deviant peer affiliation and school adaptation among 1,012 migrant children aged 12-17 years. Bootstrap test was used to evaluate the mediating effect of children's mental health. RESULTS: Deviant peer affiliation showed a significant negative impact on the school adaptation of migrant children (ß = -0.41, 95% confidence interval = -0.56 to -0.26). The relationship between deviant peer affiliation and school adaptation was partially mediated by children's mental health, resulting in an indirect effect of deviant peer affiliation on their school adaptation through their mental health (ß = -0.05, 95% confidence interval = -0.09 to -0.03). The mediating role of mental health could explain 11.4% of the relationship between deviant peer affiliation and school adaptation. CONCLUSIONS: Among migrant children, deviant peer affiliation showed unique effects on their school adaptation. Taking care of their mental health might help improve their school adaptation.

[The regulatory function of tumor-infiltrating Th9 cells to anti-tumor activity of CD8(+) T cells in patients with gastric cancer].

Objective: To investigate the levels of Th9 cells and interleukin-9 (IL-9), and to assess the regulatory activity of Th9/IL-9 to anti-tumor immune response in patients with gastric cancer. Methods: Thirty-four patients with gastric cancer who received operation in the First Affiliated Hospital of Xinxiang Medical University between October 2018 and August 2019 were included. Twenty individuals who received physical examination in the same period were also enrolled. Peripheral blood was collected, and then plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Tumor-infiltrating lymphocytes (TILs) and autologous gastric cancer cells were isolated from resected gastric cancer tissues. CD4(+) T cells, CD8(+) T cells, and CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells were purified from PBMCs and TILs. Plasma IL-9 level was measured by enzyme linked immunosorbent assay (ELISA). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs and TILSs was assessed by flow cytometry. The mRNA levels of IL-9 and transcriptional factors purine-rich nucleic acid binding protein 1 (PU.1) were semi-quantified by real-time quantitative polymerase chain reaction (RT-qPCR). PBMCs and TILs from gastric cancer patients were stimulated with recombinant human IL-9. Cellular proliferation was measured by cell counting kit-8. The phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and STAT6 were investigated by western blot. Cytokine production was measured by ELISA. Purified CD8(+) T cells from TILs of gastric cancer patients were stimulated with recombinant human IL-9. CD8(+) T cells and autologous gastric cancer cells were cocultured in direct contact and indirect contact manner. The percentage of target cell death was calculated by measuring the lactate dehydrogenase (LDH) level. These cretion of γ-Interferon (γ-IFN) and tumor necrosis factor-α (TNF-α) was measured by ELISA. CD4(+) CCR4(-)CCR6(-)CXCR3(-)cells, CD8(+) T cells, and autologous gastric cancer cells were directly cocultured, and anti-IL-9 neutralizing antibody was added. The target cell death was measured. Results: The percentages of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs of control group and PBMCs of gastric cancer group were (1.21±0.25)% and (1.14±0.19)%, respectively. The difference was not statistically significant (P=0.280). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in TILs of gastric cancer group was (2.30±0.55)%, which was higher than those in PBMCs of control group and PBMCs of gastric cancer group (P<0.001). The plasma IL-9 level in control group and gastric cancer group were (5.04±1.51) and (4.93±1.25) ng/ml. The difference was not statistically significant (P=0.787). The relative levels of IL-9 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.33±0.39 and 1.36±0.27. The difference was not statistically significant (P=0.691). The relative level of IL-9 mRNA in TILs of gastric cancer group was 2.90±0.75, which was higher than those in PBMCs of control group (P<0.001) and PBMCs of gastric cancer group (P<0.001). The relative levels of PU.1 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.21±0.12 and 1.20±0.11. The difference was not statistically significant (t=0.21, P=0.833). PU.1 mRNA relative level in TILs of gastric cancer group was 2.81±0.65, which was higher than those in PBMCs of control group (P<0.001) and PBMCs of gastric cancer group (P<0.001). Recombinant human IL-9 stimulation did not affect the proliferation of PBMCs and TILs of gastric cancer patients (P>0.05), but elevated the phosphorylation level of STAT6 and induced the secretions of γ-IFN, IL-17, and IL-22 by TILs (P<0.05). In direct contact culture system, IL-9 stimulation promoted tumor-infiltrating CD8(+) T cells-induced autologous gastric cancer cell death [(20.62±2.27)% vs. (16.08±2.61)%, P<0.01)]. In indirect contact culture system, IL-9 stimulation did not increase CD8(+) T cell-induced autologous gastric cancer cell death [(5.21±0.70)% vs. (5.31±1.22)%, P=0.998)]. However, the secretion levels of γ-IFN were elevated in response to IL-9 stimulation in both culture systems [direct contact culture system: (100.40±12.05) pg/ml vs. (76.45±8.56) pg/ml; indirect contact culture system: (78.00±9.98) pg/ml vs. (42.09±10.71) pg/ml; P<0.01]. The TNF-α secretion level did not significantly changed (P>0.05). In direct contact culture system, the percentage of target cells was (22.01±3.05) % and γ-IFN secretion level was (104.5±12.84) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group, which was higher than (16.08±2.61)% and (76.45±8.56) pg/ml in CD8(+) T cells+ gastric cancer cells group (P<0.01). However, the percentage of target cells was (14.47±3.14)% and γ-IFN secretion level was (70.45±19.43) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells+ anti-IL-9 neutralizing antibody group, which were lower than those in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group (P<0.01). Conclusion: Tumor-infiltrating Th9 cells and the secreting IL-9 promote the activity of CD8(+) T cells in gastric cancer patients, and enhance anti-tumor immune response.

[Short-term effects and seasonal variation of ozone on daily hospital outpatient visits for childhood asthma in Lanzhou].

OBJECTIVE: To analyze the effects of ozone (O3) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients. METHODS: The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O3 concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O3 concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O3 concentrations within 1 day, this study adopted different measurement approaches to address the three types of O3 exposures, namely, the maximum 1 h daily concentration (O3max1h), the maximum 8 h daily concentration (O38h) and the mean 24 h daily concentration (O324h) as the short term exposure indicators to O3, followed by a model-based analysis. RESULTS: The increase in short-term exposure levels to O3 in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 µg/m3 increase in atmospheric concentration of O3max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95%CI: 1.231%-5.516%); for every 10 µg/m3 increase in O38h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95%CI: 0.197%-3.829%); for every 10 µg/m3increase in O324h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95%CI: 0.914%-12.607%); moreover, an increase in exposure to O3max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males. CONCLUSION: The increase in short-term exposure levels to O3 in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O3max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.

[Current status and prospects of anti-angiogenic small-molecule tyrosine kinase inhibitors in the therapy of soft tissue sarcoma].

Chemotherapy is the main systemic treatment for patients with advanced soft tissue sarcoma, and immunotherapy is only effective for some special subtypes. Anti-angiogenic small molecule tyrosine kinase inhibitors represented by pazopanib and anlotinib are the main drugs of targeted therapy. They have been clearly recommended as the second-line treatment of non-specific soft tissue sarcoma in guidelines. In recent years, in addition to second-line monotherapy in patients with advanced sarcoma, some studies have been carried out in second-line combination therapy, maintenance therapy, first-line therapy and neoadjuvant therapy. This article briefly reviews the application status and prospect of anti-angiogenic small molecule tyrosine kinase inhibitors in advanced soft tissue sarcoma.

[Retrospective study on the efficacy and safety of low dose apatinib in reversing chemotherapy resistance in sarcoma].

Objective: To explore whether apatinib can reverse the chemotherapy resistance of patients with advanced sarcoma. Methods: The clinical data of advanced sarcoma patients after chemotherapy who received the original chemotherapy regimen combined with low-dose apatinib in Cancer Center of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2018 to November 2021 were collected retrospectively to evaluate the efficacy and safety of this regimen. The primary end point was progression-free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AE). The patients were grouped according to the diagnosis: osteosarcoma, soft tissue sarcoma and undifferentiated small round cell sarcoma. And the benefits of combination treatment was investigated with the stratified analysis of best outcome of combined therapy, lines of chemotherapy received, best response and PFS of original chemotherapy. Results: A total of 30 patients were included in this study, including 20 males and 10 females. The mean age was (25.6±14.7) years. There were 9 cases of osteosarcoma, 11 cases of soft tissue sarcoma and 10 cases of undifferentiated small round cell sarcoma. No patient achieved complete response, 8 patients (26.7%) achieved partial response, 19 patients (63.3%) achieved disease stability, the ORR was 26.7%(8/30), and the DCR was 90.0%(27/30). The median PFS and OS were 4.1 and 13.1 months respectively. Among the three different subtypes of sarcoma, the ORR of osteosarcoma was 44.4% (4/9), the median PFS was 4.1 months, and the median OS was not yet achieved; the ORR of undifferentiated small round cell sarcoma was 40% (4/10), the median PFS was 6.4 months, and the median OS was 10.9 months; No response was observed in soft tissue sarcoma, and the median PFS and median OS was 3.5 and 7.3 months respectively. Patients who achieved objective response had better PFS than patients with stable disease (12.8 vs 3.8 months, P=0.015), and patients with PFS≥ 6 months of original chemotherapy had better PFS benefits (12.7 vs 2.7 months, P<0.001). However, the number of original chemotherapy lines and the best response of original chemotherapy had no significant effect on the PFS of this combination regimen. In terms of safety, the related toxicity of apatinib was no more than grade 2, and the grade 4 chemotherapy-related adverse reactions was mainly hematological toxicity, of which 2 patients interrupted treatment because of febrile neutropenia. Conclusion: Low dose apatinib is effective in reversing chemotherapy resistance of osteosarcoma and undifferentiated small round cell sarcoma with acceptable adverse reactions.

[Application of TELSA structured education program in adults with type 1 diabetes mellitus].

Objective: To evaluate the effect of TELSA structured education program in adults with type 1 diabetes mellitus (T1DM) in China. Methods: From January 2019 to January 2020, 64 adult T1DM patients who met the standard of entry and had the intention to participate in TELSA structured education program were selected from the outpatient of type 1 diabetes comprehensive management in the Second Xiangya Hospital as intervention group. A total of 64 patients matched by age and sex were enrolled as the control group. During the program, the intervention group lost 3 cases and the control group lost 4 cases. Finally, there were 61 effective samples in the intervention group and 60 effective samples in the control group. The patients in the control group were given face-to-face education by a T1DM educator for about 2 hours. The patients in the intervention group were intervened according to TELSA structured education program. The level of glycosylated hemoglobin, the frequency of hypoglycemia, self-management ability and quality of life were evaluated before intervention, 6 months after intervention and 12 months after intervention. Results: The ages of the intervention group and the control group were 30.0(22.0,43.5) and 29.5(22.3,42.5) (P>0.05), and the proportions of males were 47.54%(29 cases) and 45.00%(27 cases), respectively (P>0.05). There were interaction effects (P<0.05) on the level of glycosylated hemoglobin, self-management ability and quality of life in the two groups. At 6 and 12 months after intervention of TELSA structured education program, the level of glycosylated hemoglobin in the intervention group decreased from the baseline level (7.87±1.45)% to (7.23±1.06)% and (7.28±0.93)%, respectively, which was significantly lower than that in the control group at 6 months (7.72±1.20)% and at 12 months(7.76±1.24)% (all P<0.05). After TELSA structured education intervention, the scores of self-management scale for adult type 1 diabetes mellitus (SMOD-CA) in the intervention group showed an upward trend (P<0.001), and the scores of diabetes-specific quality of life scale (A-DQOL) showed a downward trend (P<0.001). In contrast, there was no statistically significant difference in the trend of scores in the control group (P=0.853 and 0.227). The comparison between groups at different time points showed that at 6 and 12 months after the intervention, the SMOD-CA scores of the patients in the intervention group were higher than those in the control group (P<0.001), and the A-DQOL scores were lower than those in the control group (P<0.001). Conclusions: The TELSA structured education program can effectively ameliorate glycemic control, with the improvement of self-management ability and quality of life in adult T1DM patients.

[Analysis of experience in diagnosis and treatment of fetal goiter in patients with Graves' disease complicated with pregnancy].

This article reported the clinical diagnosis and treatment experience of two cases of fetal goiter in Graves' disease (GD) complicated with pregnancy. Two GD patients took antithyroid drugs regularly during pregnancy and their thyroid functions were well controlled, but the levels of thyrotropin receptor antibody (TRAb) of the two cases were still above the upper limit in the second and third trimester. Two fetuses had fetal goiter in the middle and late stages of pregnancy. After continuously controlling maternal thyroid function and closely monitoring fetal ultrasound, there was no aggravation of the fetal goiter, and the delivery went smoothly. One case had neonatal hyperthyroidism. It is suggested that although the thyroid function was well controlled during pregnancy in patients with GD, the high level of serum TRAb still needs to be alert to the occurrence of fetal goiter, and fetal ultrasound is the most direct non-invasive monitoring method.

[Analysis of resistance and sensitivity of 1 200 strains of vulvovaginal candidiasis in China to five common antifungal drugs].

Objective: To test the antibiotic susceptibility of vulvovaginal candidiasis pathogenic strains to 5 antifungal drugs commonly used in clinic. Methods: A total of 1 200 vulvovaginal candida patients from 23 gynecological and family planning outpatient departments in China were enrolled. Their vaginal secretions were collected for candida strain isolation and species identification. According to Clinical and Laboratory Standards Institute (CLSI) M27-S3, the sensitivity of 1 200 strains to clotrimazole, fluconazole, miconazole, itraconazole and nystatin was tested. Results: (1) The sensitivity and resistance of 1 200 vulvovaginal candidiasis pathogens to 5 antifungal drugs were statistically different (χ2=3 513.201, P<0.01). (2) All strains had higher sensitivity to nystatin [99.92% (1 199/1 200)], followed by miconazole [92.25% (1 107/1 200)] and clotrimazole [87.17% (1 046/1 200)]. All strains had higher resistance to fluconazole [69.17% (830/1 200)], while itraconazole was 50.83% (610/1 200). (3) There was no significant difference between candida albicans and non-candida albicans in drug sensitivity to nystatin (P=0.315) and miconazole (P=0.425). (4) Candida albicans and non-candida albicans showed different sensitivity to clotrimazole, fluconazole and itraconazole, respectively. Compared with non-candida albicans, candida albicans showed higher sensitivity to clotrimazole [susceptibility rate: 73.01% (165/226) vs 90.45% (881/974); P<0.001] and higher resistance to fluconazole [resistance rate: 50.88% (115/226) vs 73.41% (715/974); P<0.001]. Although the drug sensitivity of itraconazole was not high, the susceptibility rate of candida albicans to itraconazole was slightly higher than that of non-candida albicans [37.68% (367/974) vs 23.89% (54/226)], and the drug resistance rate was lower [49.28% (480/974) vs 57.52% (130/226)]. Conclusions: The sensitivity of 1 200 strains of candida to 5 antifungal drugs is significantly different, the sensitivity rate of nystatin, miconazole and clotrimazole are higher, but the resistance rate of fluconazole and itraconazole are higher. The sensitivity of candida albicans and non-candida albicans to the same drug is also significantly different. It is suggested that in clinical diagnosis and treatment, we should pay attention to the identification of candida and drug sensitivity test, so as to select antifungal drugs rationally.

[Prediction and analysis of adverse pregnancy outcomes in pregnant women with cesarean scar diverticulum].

Objective: To investigate the pregnancy outcomes of pregnant women with cesarean scar diverticulum (CSD) and to find the relevant factors that predict the occurrence of adverse pregnancy outcomes. Methods: From January 2015 to March 2019, 501 singleton pregnant women with a history of cesarean section who underwent regular prenatal examination in early pregnancy and eventually delivered in Peking University First Hospital were prospectively collected. According to the presence or absence of CSD in the first trimester of pregnancy, the pregnant women were divided into the CSD group (n=127, 25.3%) and the non-CSD group (n=374, 74.7%). According to the mode of delivery and the classification of the lower uterine segment seen during cesarean section, the CSD group was further divided into the non-rupture group (including spontaneous delivery and lower uterine segment grade Ⅰ;n=108, 85.0%) and rupture group (including lower uterine segment grade Ⅱ-Ⅳ;n=19, 15.0%). The general clinical data, pregnancy outcomes, diverticulum-related indexes [including length, width, depth (D), average diameter, volume, and residual myometrial thickness (RMT)] were compared. The predictive values of D/adjacent myometrial thickness≥50%, RMT≤2.2 mm and D/RMT>1.3 for uterine rupture in CSD pregnant women were verified. Results: (1) Comparison between CSD group and non-CSD group: the lower uterine segment thickness in the third trimester of pregnancy in the CSD group was lower than that in the non-CSD group [(1.2±0.5) vs (1.4±0.6) mm, respectively], and the incidence of uterine rupture was higher than that in the non-CSD group [15.0% (19/127) vs 8.0% (30/374), respectively], and the differences were statistically significant (both P<0.05). There were no significant differences in other clinical data and pregnancy outcomes between the two groups (all P>0.05). (2) Comparison of rupture group and non-rupture group: the lower uterine segment thickness in the third trimester of pregnancy in rupture group [(0.6±0.5) mm] was lower than that in non-rupture group [(1.2±0.6) mm], and the difference was statistically significant (t=3.486, P=0.001). There were no significant differences in diverticulum-related indexes between the two groups (all P>0.05). (3) Relationship between high risk predictors of uterine rupture and actual uterine rupture: the sensitivity of D/adjacent muscle thickness ≥50%, RMT≤2.2 mm and D/RMT>1.3 in predicting the high risk of uterine rupture were 94.7%, 57.9% and 73.6%, the specificity were 12.0%, 40.7% and 24.1%, the positive predictive value were 15.9%, 14.7%, 14.6%, and the negative predictive value were 92.8%, 84.6%, 83.9%, respectively. Conclusions: The risk of uterine rupture in pregnant women with CSD is higher than that in those without CSD. There is no significant correlation between CSD related indexes and uterine rupture in the first trimester. Monitoring the lower uterine segment thickness in the third trimester might be helpful to predict the occurrence of adverse pregnancy outcomes.

[Lipid metabolism in idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology, which was characterized by irreversible lung function decrease and high mortality. Up till now, only two drugs, i.e. Pirfenidone and Nintedanib,have been approved by Food and Drug Administration (FDA) for therapy of IPF, and the treatment is less effective. Therefore, it is urgent to develop new therapeutic drugs. In recent years, studies had paid attention to lipid metabolism in IPF. In this review, we discussed recent major advances of lipid metabolism, biomarkers and clinical trials in IPF.