Blood cell count-derived inflammation indices as predictors of the osteoporotic risk of postmenopausal women.

OBJECTIVE: We investigated the associations between osteoporosis (OP) and systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in postmenopausal women. PATIENTS AND METHODS: This retrospective study included 966 postmenopausal women. Logistic regression and receiver operating characteristic curve (ROC) analyses were applied to explore the relationships between SII, NLR, MLR, and PLR with the bone mineral density (BMD) and risk of OP. RESULTS: Logistic regression analyses showed that SII, PLR, NLR, and MLR had independent negative associations with the OP risk. The ROC curve analysis showed that SII, NLR, and MLR predicted a low BMD, with NLR having the highest predictive value (area under the curve = 0.624). SII > 504.09, PLR > 131.87, NLR > 2.02, and MLR > 0.12 correlated with a particularly high OP risk. CONCLUSIONS: High levels of SII, PLR, NLR, and MLR were associated with a high OP risk. In particular, NLR > 2.02 strongly predicted the risk of OP, thereby representing a valuable and convenient inflammatory marker of the OP risk.

[Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model].

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Source apportionment and ozone formation mechanism of VOCs considering photochemical loss in Guangzhou, China.

Understanding the sources and impact of volatile organic compounds (VOCs) on ozone formation is challenging when the traditional method does not account for their photochemical loss. In this study, online monitoring of 56 VOCs was carried out in summer and autumn during high ozone pollution episodes. The photochemical age method was used to evaluate the atmospheric chemical loss of VOCs and to analyze the effects on characteristics, sources, and ozone formation of VOC components. The initial concentrations during daytime were 5.12 ppbv and 4.49 ppbv higher than the observed concentrations in the summer and autumn, respectively. The positive matrix factorization (PMF) model identified 5 major emission sources. However, the omission of the chemical loss of VOCs led to underestimating the contributions of sources associated with highly reactive VOC components, such as those produced by biogenic emissions and solvent usage. Conversely it resulted in overestimating the contributions from VOC components with lower chemical activity such as liquefied petroleum gas (LPG) usage, vehicle emissions, and gasoline evaporation. Furthermore, the estimation of ozone formation may be underestimated when the atmospheric photochemical loss is not taken into account. The ozone formation potential (OFP) method and propylene-equivalent concentration method both underestimated ozone formation by 53.24 ppbv and 47.25 ppbc, respectively, in the summer, and by 40.34 ppbv and 26.37 ppbc, respectively, in the autumn. The determination of the ozone formation regime based on VOC chemical loss was more acceptable. In the summer, the ozone formation regime changed from the VOC-limited regime to the VOC-NOx transition regime, while in the autumn, the ozone formation regime changed from the strong VOC-limited regime to the weak VOC-limited regime. To obtain more thorough and precise conclusions, further monitoring and analysis studies will be conducted in the near future on a wider variety of VOC species such as oxygenated VOCs (OVOCs).

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Causal relationship between Type 1 diabetes and osteoporosis and fracture occurrence: a two-sample Mendelian randomization analysis.

We used two-sample Mendelian Randomization to reveal causal estimates of type 1 diabetes and bone. Type 1 diabetes was found to be a risk factor for bone metabolic health, although there was no clear evidence to support a genetic association between type 1 diabetes and osteoporosis and fracture risk. INTRODUCTION: Based on the random assignment of gametes at conception, Mendelian randomization (MR) analysis simulates randomized controlled trials in an observational setting. Therefore, we used MR to assess the association causality of type 1 diabetes (T1D) with fractures and osteoporosis. METHODS: From a genome-wide association meta-analysis, independent single nucleotide polymorphisms closely associated with T1D were selected as instrumental variables. Data on fracture and osteoporosis were obtained from the FinnGen Consortium. We performed a two-sample MR analysis, using inverse-variance weighted (IVW) as the primary analysis method, to assess possible causal associations between T1D and bone risk. The results were verified by MR-Egger regression and median weighted method (WME). MR-PRESSO and MR-Egger intercepts were used to evaluate the horizontal pleiotropy of instrumental variables, and the Q-test and "leave-one-out" methods were used to test the heterogeneity of MR results. RESULTS: IVW (OR=1.040, 95% CI=0.974-1.109, P=0.238), MR-Egger regression (OR=1.077, 95% CI=0.921-1.260, P=0.372) and WME (OR=1.021, 95% CI=0.935-1.114, P=0.643) all showed that there was no causal relationship between T1D and osteoporosis, but the direction was consistent. The indicative significance of IVW results in T1D and forearm fractures (OR=1.062, 95% CI=1.010-1.117, P=0.020), but the results are not robust enough. There was no causal effect in femur, lumbar and pelvis, or shoulder and upper arm fractures. CONCLUSIONS: After MR analysis, although T1D may be a risk factor for bone health, we do not have sufficient evidence to support a causal effect of T1D on osteoporosis and fractures at a genetically predicted level. More cases need to be included for analysis.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

[Clinicopathological festures and outcome of combined hepatocellular-cholangiocarcinoma].

Objective: To investigate the clinicopathological features and pathological types and outcome of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Methods: 30 cases of cHCC-CC were collected from Jan 2007 to Jun 2021 at General Hospital of Southern Theatre Command, People's Liberation Army of China, and analyzed the clinicopathological features, immunohistochemistry and outcome. The histological morphology was classified according to the Goodman standard and the fifth edition of World Health Organization (WHO) classification of digestive system tumors. Results: According to the Goodman classification, 9 cases belonged to type Ⅰ (i.e., collision tumor), with a coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma in the same specimen, and 21 cases were Type Ⅱ or "transitional tumors", in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. According to the WHO classification of digestive system tumors (5th Edition), 25 cases were classified in cHCC-CC, and 5 cases were cHCC-CC-Intermediate cell carcinoma. There were 28 males and 2 females, with an average age of 50.4 (31-72) years old. 21 cases accompanied liver cirrhosis, with liver flukes in 1 case and HBsAg positive in 23 cases. Immunohistochemical staining showed nestin was positive in 9 cases, 66.7% died (6/9) and 33.3% (3/9) survived only 6 months. The 1-year recurrence rate was 3.9% for liver resection and 50% for orthotopic liver transplantation, and liver resection has longer median survival time than liver transplantation after recurrence. Conclusions: cHCC-CC is a rare type of primary liver malignant tumor. Preoperative diagnosis is difficult. The definite diagnosis depends on histopathological morphology and immunohistochemical markers. Nestin may be as a prognosis factor, and surgical treatment is preferably liver resection.

[Cell heterogeneity of laryngeal carcinoma and evolution trajectory of epithelial cells].

Objective: To analyze the classification and functions of cell subsets in laryngeal carcinoma and metastatic lymph nodes, and to explore the evolution trajectory of epithelial cells to tumor cells. Methods: Single-cell RNA sequencing was performed on 5 cases of laryngeal cancer, matched metastatic lymph nodes and 3 normal tissues. Patients were admitted to Ningbo Medical Center Lihuili Hospital from October 22, 2019 to December 16, all patients were male, aged 53-70 years old. Cell subsets of the above-mentioned tissues were analyzed by the Seurat, and the biological functions of cell subpopulation were investigated by functional enrichment analysis. Malignant epithelial cells were identified using copy number variation (CNV). The evolutionary trajectory of epithelial cells to cancer cells was analyzed by cell trajectory analysis, and cancerous transitional cells were identified. The highly expressed genes in transitional cells were analyzed by the FindAllMarker of the Seurat and verified by immunohistochemistry. Results: A total of 66 969 high-quality cells were obtained in 9 major clusters: epithelial cells, T cells, B cells, fibroblasts, endothelial cells, myeloid cells, mast cells, plasmacytoid dendritic cells and nerve cells. The first 5 cell clusters were divided into 8, 6, 4, 3 and 2 subgroups, respectively. Four epithelial cell subsets (C0, C1, C2 and C5) were derived from tumor tissues and metastatic lymph nodes, and had high levels of CNV and tumor cell content. Cell trajectory analysis showed that the evolution trajectory of epithelial cells was from normal epithelial subpopulation C4 to early cancerous cell population C0, which differentiated into three major malignant cell subsets C1, C3, and C5. Epithelial cell C0 may represent the transitional cell population of carcinogenesis, and were enriched in biological processes such as epithelial-mesenchymal transformation and angiogenesis. C0 highly expressed sulforaphane (SFN) which may be related to the occurrence and development of cancer. Immunohistochemistry confirmed that SFN was highly expressed in tumor tissues and metastatic lymph nodes compared with paracancerous tissues. Conclusion: Single-cell sequencing may be used to elucidate the diversity of cells and functions in laryngeal carcinoma tissues and metastatic lymph nodes, and cell population C0 plays a key role in the evolution of cells.

[China guideline for the screening and early detection of prostate cancer (2022, Beijing)].

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

[Clinical features and prognostic value of TP53 mutation in Chinese prostate cancer patients].

Objective: To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods: A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95%CI associated with PFS. Results: In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ²=4.829, P=0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ²=8.434, P=0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone(HR=2.23, 95%CI: 1.26 to 3.94, P=0.006) and docetaxel(HR=1.92, 95%CI: 1.01 to 3.66, P=0.047) had significant differences in PFS. Conclusions: TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.

[A new classification of intrahepatic cholangiocarcinoma based on actual anatomy:a series of 135 cases].

Objective: To explore the feasibility and clinical value of a new classification for resectable intrahepatic cholangiocarcinoma (IHCC) according to the actual anatomy. Methods: The data of 135 patients with IHCC who were admitted to the Department of Hepatopancreatobiliary Surgery,Second Affiliated Hospital of Zhejiang University School of Medicine from November 2011 to November 2020 after discussion by a multidisciplinary team and planned to undergo radical resection were analyzed retrospectively. There were 77 males and 58 females,with a median age of 61 years (range:26 to 86 years),of which 38 cases had vascular invasion. This new classification was carried out independently by two hepatobiliary surgeons. First,a preliminary classification was made based on the location of the tumor,and then the final classification was based on vascular invasion. All patients were followed up by telephone,and the follow-up was as of November 2020. Survival time is defined as the time after surgery to follow-up or death. Log-rank test was used to compare patients' median recurrence-free survival and overall survival time. The Cox proportional hazard model was used to analyze the prognosis factors of the overall survival time of patients with IHCC. Results: Among the 135 patients,129 underwent R0 resection and 6 underwent R1 resection. According to the actual anatomy,28 cases (20.7%) belonged to segmental type, 43 cases (31.9%) belonged to branch type, 64 cases (47.4%). The median survival time of all patients was 35.2 months(95%CI:21.3 to 70.5 months),the 1-year cumulative survival rate was 75.1%,the 3-year cumulative survival rate was 45.8%,and the 5-year cumulative survival rate was 39.0%. After grouping according to the classification,the median survival time of segmental patients was 36.9 months (more than 50% of patients reached the median survival time),and the median survival time of branched patients was 33.8 months (95%CI:16.8 to 38.5);The median survival time of lobe patients was 25.0 months (95%CI:13.6 to 58.7). The result of Log-rank test between groups indicated that the median survival time of patients with segmental type was better than that of patients with branch and lobe type(HR=2.03,95%CI:1.24 to 3.64,P=0.006);There was no significant difference in survival time between patients with branch type and lobe type (P=0.685). The results of the multivariate analysis of the Cox risk ratio model suggested that the actual anatomical location classification (HR=2.32,95%CI:1.10 to 4.92,P=0.028) and the postoperative lymph node metastasis rate (HR=2.06,95%CI:1.24 to 3.45,P=0.005) were independent factors related to survival after radical resection of IHCC patients. Conclusion: It is simple and convenient to classify resectable IHCC by actual anatomy,which can be used to preliminarily judge the prognosis of patients and provide a feasible classification scheme for the clinic.

Uncertainty quantification patterns for multiscale models.

Uncertainty quantification (UQ) is a key component when using computational models that involve uncertainties, e.g. in decision-making scenarios. In this work, we present uncertainty quantification patterns (UQPs) that are designed to support the analysis of uncertainty in coupled multi-scale and multi-domain applications. UQPs provide the basic building blocks to create tailored UQ for multiscale models. The UQPs are implemented as generic templates, which can then be customized and aggregated to create a dedicated UQ procedure for multiscale applications. We present the implementation of the UQPs with multiscale coupling toolkit Multiscale Coupling Library and Environment 3. Potential speed-up for UQPs has been derived as well. As a proof of concept, two examples of multiscale applications using UQPs are presented. This article is part of the theme issue 'Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification in silico'.

[Survival status and influencing factors of HIV/AIDS cases in Liuzhou, 2008-2018].

Objective: To understand the duration of survival and related influencing factors of HIV/AIDS patients in Liuzhou city. Methods: Both life table method and Kaplan-Meier method were used to calculate the average survival time of HIV/AIDS patients aged ≥15 years reported in Liuzhou city from 2008 to 2018. Factors related to the duration of HIV/AIDS patients were analyzed by univariate and multivariate Cox regression models. Results: A total of 14 856 patients with HIV/AIDS were involved in this study and with the average duration of survival time as 98.74 (95%CI: 97.73-99.75) months. The cumulative survival rates of 1, 3, 5 and 10 years were 77.0%, 72.0%, 68.0%, 61.0% respectively. Results from the multivariate Cox proportional risk regression analysis showed that factors as sex, level of education, age when HIV infection was confirmed, occupation, route of transmission, source of samples, results of the first CD(4) test and antiviral treatment were all related to the duration of survival to the HIV/AIDS patients. Conclusions: Strategies involving early detection of HIV infection, improvement of the CD(4) initial detection rate and early antiviral treatment will help to significantly reduce the risk of death in HIV/AIDS population. Focus should be on male, middle-aged and elderly (over 41 years old), junior high school education or below farmers and migrant worker populations.

Management of Intrauterine Device Migrated into the Bladder: A Case Report and Literature Review.

Intrauterine device represents the most reversible method of contraceptive worldwide. Its insertion is a medical procedure not free from complication. We report a rare case of intravesical migration of a copper intrauterine device inserted 18 months earlier in a 28-year-old multiparous woman. The patient presented with irritative lower urinary tract symptoms, and she was managed endoscopically. This case underscores the role of cystoscopy in irritative lower urinary tract symptoms post IUD insertion.

SCH58261, the antagonist of adenosine A2A receptor, alleviates cadmium-induced preeclampsia via sirtiun-1/hypoxia-inducible factor-1α pathway in rats.

OBJECTIVE: To identify the role of adenosine A2A receptor (A2AR) in cadmium-induced preeclampsia (PE) rats and the potential molecular mechanism. PATIENTS AND METHODS: The expression of A2AR in placentae obtained from PE women and normal pregnant (NP) women were measured. The pregnant rats were randomly divided into four groups, including NP rats, PE rats, SCH+NP rats, and SCH+PE rats. The 0.125 mg/kg/d CdCl2 was used to establish a PE rat model in PE and SCH+PE rats. SCH58261 was used as the specific antagonist of A2AR with a concentration of 0.2 mg/kg in SCH+NP and SCH+PE rats. The conditions of mother, foetus, and placenta were tested. The placental expression of A2AR, sirtuin-1 (sirt1), and Hypoxia-Inducible Factor-1α (HIF-1α) was measured by Western blot (WB) and immunohistochemistry (IHC) staining. RESULTS: A2AR and HIF-1α increased, and sirt1 decreased in placenta in both PE women and cadmium-induced PE rats. After treatment with SCH58261, the sirt1 increased and HIF-1a decreased in cadmium-induced PE rats along with the amelioration of maternal outcomes, foetal and placental growth. CONCLUSIONS: This paper firstly revealed that placental A2AR mediated cadmium-induced PE, and A2AR suppression could attenuate placental impairment by acting on the expression of sirt1 and sirt1-mediated regulation of HIF-1α.

Genome-wide association study of bone mineral density trait among three pig breeds.

Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e-14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.

[Significance of expression of Myc-induced nuclear antigen 53 in hepatocellular carcinoma and its relationship with patient prognosis].

Objective: To detect the expression of Myc-induced nuclear antigen 53 (Mina53) and liver tissue >5 cm from the edge of the tumor (LTM5), and analyze its relationship with tumorigenesis, clinicopathological characteristics, and patient survival and prognosis in hepatocellular carcinoma (HCC). Methods: The expression levels of Mina53 mRNA and protein in 18 pairs of fresh HCC and LTM5 were assessed by qRT-PCR and Western blot, respectively. The expression of Mina53 in 284 pairs of HCC and LTM5 sample was determined by immunohistochemistry. Paired-sample t-test was used for the comparison of measurement data among groups, and heterogeneity of variance was tested using Wilcoxon rank-sum test. χ (2) test was used for the comparison of measurement data among groups. Kaplan-Meier method and log-rank test were used for survival analysis. Cox regression model was used for single factor and multi factor analysis. Results: The relative expression levels of Mina53 mRNA and protein in 18 fresh HCC tissues were significantly higher than those in LTM5 tissues (mRNA: -4.41 ± 1.48 and -5.93 ± 1.65, t = 3.100, P = 0.007; protein: 1.12 ± 0.29 and 0.46 ± 0.21, t = 10.616, P < 0.001). The relative expression level of Mina53 in 284 HCC tissues was higher than that of LTM5 (z = -18.739, P < 0.001). The expression level of Mina53 was associated with tumor size (χ (2) = 5.474, P = 0.019), vascular invasion (χ (2) = 8.965, P = 0.003), pathological grade (χ (2) = 12.006, P = 0.002), and TNM stage (χ (2) = 16.686, P < 0.001). The overall postoperative survival time and disease-free survival time of patients with high expression of Mina53 (28.5 months and 22.7 months, respectively) were shorter than those with low expression (33.0 months and 31.8 months, respectively) (P < 0.05) in HCC. Cox multivariate regression analysis showed that Mina53 and multiple tumors were independent prognostic factors affecting the overall postoperative survival time and disease-free survival time of HCC patients (P < 0.05). Conclusion: Mina53 may play an important role in the occurrence of HCC and participate in the process of tumor growth as well as invasion and metastasis. The high expression of Mina53 signifies that the patient has a poor prognosis and thus can be used as a potential marker for judging the prognosis of HCC patients.

Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene.

PURPOSE: T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxine-binding globulin deficiency. METHODS: A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. RESULTS: TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p < 0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p < 0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION: Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.

[Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report].

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.