Social Network Characteristics Associated with More Frequent HIV and STI Prevention Conversations: The N2 Cohort Study in Chicago.

Black cisgender sexually minoritized men (SMM) and transgender women (TW) are subgroups at highest risk of HIV and sexually transmitted infections (STIs) in the US. We sought to identify factors facilitating continued conversations - social reinforcement - surrounding HIV/STI prevention among this subgroup. Participants were recruited in Chicago from 2018 to 2019 from community health spaces. Participants provided information about themselves (level 2) and ⩽5 confidants (level 1). We used multinomial multilevel modeling to identify associations with HIV/STI prevention conversation frequency. A total of 370 participants provided information on 987 confidants (mean = 2.6). We found significantly positive associations between having biweekly or more often HIV/STI prevention conversations and a confidant being a kin family member, older by 15 years or more, racially homophilous, and emotionally close. Future interventions should harness social networks by including components that consider racial homophily, respect for elders, and strong ties, in addition to applying kin family systems interventions approaches and decreasing stigma surrounding HIV/STIs.

[Advances in the application of the bony window technique in endodontic microsurgery].

The bony window technique refers to cutting the intact bone plate to form a bone window and a free bone block to get access to lesions under the bone. At the end of the surgery, the dislocated bony lid needs to be repositioned to its original position. In endodontic microsurgery, compared with conventional osteotomy, the bony window technique has the advantages of improving the view of surgery and operability, reducing postoperative bone defects, promoting bone healing, and maintaining the integrity of the jaw outline. Accurate positioning and preparation of the bony window are important prerequisites for subsequent operations during the surgery, but it's difficult in some situations, such as when the operative area is located posteriorly or the bone cortex on the lesion surface is thick and intact. What's more, whether the free bone block can be stabilized in situ after repositioning is closely related to the prognosis of the surgery. The complementary application of digital navigation technology and bone cavity filling materials may help to improve the bony window technique and provide more possibilities for the retention of affected teeth in difficult cases.

Network pharmacological and molecular docking verification of the mechanism of Osteoking in preventing deep vein thrombosis of lower limb.

OBJECTIVE: The aim of this study was to predict the mechanism of Osteoking in preventing deep vein thrombosis (DVT) of the lower limb by network pharmacology and molecular docking. MATERIALS AND METHODS: The relevant active components and targets of Osteoking were collected through the TCMSP database, and the relevant disease targets of DVT were collected through the GeneCards, OMIM, and DisGeNET databases. The intersecting gene targets of Osteoking and DVT were obtained using Venny 2.1.0 software. PPI network construction and core target selection using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of relevant targets. Finally, the molecular docking of the main active components and key targets was carried out. RESULTS: There are 361 potential targets and 71 core targets of Osteoking in preventing deep vein thrombosis of the lower limb. Signal pathways are involved in various diseases such as cancer, diabetic complications, atherosclerosis, and more. Some of the most common pathways include AGE-RAGE signaling pathway and Calcium signaling pathway. Molecular docking results showed that the main active components of Osteoking had relatively stable binding activities with the key targets. CONCLUSIONS: Osteoking can play a role through multiple targets and multiple signal pathways to prevent the formation of deep venous thrombosis of the lower limb after fracture.

Diagnostic efficacy of lung ultrasound in cardiogenic pulmonary edema: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the diagnostic efficacy of lung ultrasound (LUS) in cardiogenic pulmonary edema. MATERIALS AND METHODS: An electronic search of databases, including MEDLINE, Embase, PubMed, and Web of Science, was performed to collect clinical studies on ultrasound diagnosis of cardiogenic pulmonary edema from inception to 23 March 2023. The number of patients with true-positive, true-negative, false-positive, and false-negative cardiogenic pulmonary edema diagnosed by LUS was collected, and the R package was used to analyze the diagnostic efficacy of LUS. RESULTS: Nine pieces of literature were finally included with 2,097 participants, including 1,047 patients with cardiogenic heart failure. Across the nine included papers, the pooled sensitivity of LUS in the included studies was 0.92 (95% CI: 0.84, 0.97) with a maximum sensitivity of 0.99 (95% CI: 0.96 to 1.00) and a minimum of 0.59 (95% CI: 0.50, 0.68). The pooled specificity of the included studies was 0.87 (95% CI: 0. 82, 0.91) with a maximum specificity of 0.93 (95% CI: 0.90-0.95) and a minimum of 0.80 (95% CI: 0.67, 0.89). The pooled AUC was 0.93 (95% CI: 0.84 to 0.97), suggesting a high diagnostic value of LUS in cardiogenic pulmonary edema. CONCLUSIONS: Lung ultrasound offers a good diagnostic efficacy for cardiogenic pulmonary edema. Further standardization of the examination method is required to provide a reference for the clinical use of LUS.

[Regulating the immune response to carbon tetrachloride-induced liver fibrosis in mice by blocking inducible co-stimulatory molecules and interleukin-33].

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.

[Factors associated with readmission within three months of surgery for gastric cancer and their long-term effects on patients' nutritional status and quality of life].

Objective: To analyze the factors associated with readmission within three months of surgery for gastric cancer and the impact of readmission on patients' long-term nutritional status and quality of life. Methods: This was a prospective cohort study comprising patients who underwent radical gastrectomy in the Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from October 2018 to August 2019. Patients who failed to complete postoperative follow-up, whose body mass index (BMI) could not be accurately estimated, or who were unable to complete a quality-of-life questionnaire were excluded. The patients were followed up for 12 months. Time to, cause(s) of, and outcomes of readmission were followed up 1, 2 and 3 months postoperatively. BMI was followed up 1, 3, 6 and 12 months postoperatively. Results of blood tests were collected and patients' nutritional status and quality of life were assessed 12 months postoperatively. Nutritional status was evaluated by BMI, hemoglobin, albumin, and total lymphocyte count. Quality of life was evaluated using the European Organization for Research in the Treatment of Cancer (EORTC) Quality of Life scale. The higher the scores for global health and functional domains, the better the quality of life, whereas the higher the score in the symptom domain, the worse the quality of life. Results: The study cohort comprised 259 patients with gastric cancer, all of whom were followed up for 3 months and 236 of whom were followed up for 12 months. Forty-four (17.0%) patients were readmitted within 3 months. The commonest reasons for readmission were gastrointestinal dysfunction (16 cases, 36.3%), intestinal obstruction (8 cases, 18.2%), and anastomotic stenosis (8 cases, 18.2%). Logistic regression analysis showed that preoperative Patient-Generated Subjective Global Assessment score ≥ 4 points (OR=1.481, 95% CI: 1.028‒2.132), postoperative complications (OR=3.298, 95%CI:1.416‒7.684) and resection range (OR=1.582, 95% CI:1.057‒2.369) were risk factors for readmission within 3 months of surgery. Compared with patients who had not been readmitted 12 months after surgery, patients who were readmitted within 3 months of surgery tended to have greater decreases in their BMI [-2.36 (-5.13,-0.42) kg/m2 vs. -1.73 (-3.33,-0.33) kg/m2, Z=1.850, P=0.065), significantly lower hemoglobin and albumin concentrations [(122.1±16.6) g/L vs. (129.8±18.4) g/L, t=2.400, P=0.017]; [(40.9±5.0) g/L vs. (43.4±3.3) g/L, t=3.950, P<0.001], and significantly decreased global health scores in the quality of life assessment [83 (67, 100) vs. 100 (83, 100), Z=2.890,P=0.004]. Conclusion: Preoperative nutritional risk, total or proximal radical gastrectomy, and complications during hospitalization are risk factors for readmission within 3 months of surgery for gastric cancer. Perioperative management and postoperative follow-up should be more rigorous. Readmission within 3 months after surgery may be associated with a decline in long-term nutritional status and quality of life. Achieving improvement in long-term nutritional status and quality of life requires tracking of nutritional status, timely evaluation, and appropriate interventions in patients who need readmission.

[Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma].

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

[Effects of bariatric surgery on sex hormones in male patients with obesity].

Objective: To analyze and evaluate the differences in sex hormones after laparoscopic Roux-en-Y Gastric Bypass Surgery (LRYGB) and laparoscopic sleeve gastrectomy (LSG) in male patients with obesity. Methods: This study was a retrospective cohort study. The inclusion criteria were (1) male patients with obesity who met the surgical indications of the "Chinese Guidelines for Surgical Treatment of Obesity and Type 2 Diabetes" (2019 Edition); (2) patients with a body mass index (BMI) of ≥27.5 kg/m2 and obesity-related metabolic diseases, or patients with severe obesity and a BMI of ≥35 kg/m2; and (3) sex hormone levels checked 1 year after surgery. The exclusion criteria included (1) patients with endocrine diseases (thyrotoxicosis, hyperprolactinemia) and hypothalamic-pituitary lesions and (2) those with severe major organ dysfunction who could not tolerate anesthesia or surgery. According to the above criteria, the clinical data of male patients with obesity admitted to the Gastrointestinal Surgery/Bariatric Center of the First Affiliated Hospital of Jinan University from October 2017 to January 2020 were included. A total of 52 male patients with obesity were included in this study. The mean age, body weight, BMI, and total testosterone level were (29.3±10.2) years, (123.6±35.4) kg, (40.1±11.1) kg/m2, and 7.6 (5.5, 9.1) nmol/L, respectively. Forty-five patients (86.5%) exhibited testosterone deficiency. Among all the patients, 29 underwent LSG (LSG group) and 23 underwent LRYGB surgery (LRYGB group). The main outcome measure was the change in sex hormone levels before and after bariatric surgery in all the patients. The secondary outcome measures were the comparison of changes in sex hormone levels before and after LSG and LRYGB. Results: Pearson correlation analysis showed that preoperative estradiol was positively correlated with waist circumference (R=0.299, P<0.05), hip circumference (R=0.326, P<0.05), and chest circumference (R=0.388, P<0.05). Testosterone was negatively correlated with BMI (R=-0.563, P<0.01), waist circumference (R=-0.521, P<0.01), hip circumference (R=-0.456, P<0.01), chest circumference (R=-0.600, P<0.01), and neck circumference (R=-0.547, P<0.01). One year following bariatric surgery, the serum testosterone (7.6 [5.5, 9.1] nmol/L vs. 13.6 [10.5, 15.4] nmol/L, Z=-5.910, P<0.001), follicle-stimulating hormone (4.7 [2.7, 5.3] IU/L vs. 6.5 [3.6, 7.8] IU/L, Z=-4.658, P<0.001), and progesterone (1.2 [0.4, 1.5] nmol/L vs. 1.9 [0.8, 1.3] nmol/L, Z=-2.542, P=0.011) levels were significantly higher in all the patients. Both estradiol (172.8 [115.6, 217.5] pmol/L vs. 138.3 [88.4, 168.1] pmol/L, Z=-2.828, P=0.005) and prolactin (11.4 [6.4, 14.6] mIU/L vs. 8.6 [4.8, 7.3] mIU/L, Z=-2.887, P=0.004) levels were decreased. In addition to prolactin levels in the LRYGB group, there were statistically significant differences in the levels of estradiol (P=0.030), follicle-stimulating hormone (P < 0.001), luteinizing hormone (P=0.033), progesterone (P=0.034), and testosterone (P<0.001) compared with their preoperative levels. In the LSG group, there were statistically significant differences in the levels of follicle-stimulating hormone (P=0.011), prolactin (P=0.023), and testosterone (P<0.001) compared with their preoperative levels. Conclusion: The degree of obesity in men was negatively correlated with testosterone levels. Both LRYGB and LSG can significantly improve sex hormone levels in male patients with obesity, and testosterone levels show a significant increase after surgery.

[Chinesization of the quality of life scale and its reliability and validity tests for non-alcoholic fatty liver disease].

Objective: To translate the English version of the non-alcoholic fatty liver disease quality of life scale (CLDQ-NAFLD) into the Chinese version in order to test its reliability and validity. Methods: The English version of the CLDQ-NAFLD was translated according to the cross-cultural research tool debugging and validation guidelines to form the Chinese version of the CLDQ-NAFLD. A questionnaire survey was conducted on 515 NAFLD cases in a tertiary hospital in Hangzhou from September 2021 to April 2022 to evaluate the reliability and validity of the scale. Results: The Chinese version of the CLDQ-NAFLD contained six domains with a total of thirty-six items (X2/DF=3.105, RMSEA=0.064, TLI=0.905, CFI=0.912, and IFI=0.913). I-CVI, S-CVI/UA, and S-CVI/Ave was 0.83 to 1.00, 0.86 and 0.98, respectively. The 12-item Short-Form Health Survey (SF-12) was used as the calibration standard, and the correlation validity of the calibration standard was 0.704 (P<0.001). The Cronbach's alpha coefficient of the total scale and each dimension of the scale was 0.964 and 0.807-0.956, respectively. The test-retest reliability was 0.839. Conclusion: The Chinese version of the CLDQ-NAFLD has good reliability and validity. Thus, it can be used to evaluate the quality of life for NAFLD patients with a Chinese cultural background.

[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.

Laser-cooled 171Yb+ microwave frequency standard with a short-term frequency instability of 8.5 × 10-13/√τ.

We report on the development of a microwave frequency standard based on a laser-cooled 171 Y b + ion trap system. The electronics , lasers, and magnetic shields are integrated into a single physical package. With over 105 ions are stably trapped, the system offers a high signal-to-noise ratio Ramsey line-shape. In comparison with previous work, the frequency instability of a 171 Y b + microwave clock was further improved to 8.5×10-13/τ for averaging times between 10 and 1000 s. Essential systematic shifts and uncertainties are also estimated.

Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

Search for B

A search for the flavor-changing neutral-current decay B^{+}→K^{+}νν[over ¯] is performed at the Belle II experiment at the SuperKEKB asymmetric energy electron-positron collider. The data sample corresponds to an integrated luminosity of 63 fb^{-1} collected at the ϒ(4S) resonance and a sample of 9 fb^{-1} collected at an energy 60 MeV below the resonance. Because the measurable decay signature involves only a single charged kaon, a novel measurement approach is used that exploits not only the properties of the B^{+}→K^{+}νν[over ¯] decay, but also the inclusive properties of the other B meson in the ϒ(4S)→BB[over ¯] event, to suppress the background from other B meson decays and light-quark pair production. This inclusive tagging approach offers a higher signal efficiency compared to previous searches. No significant signal is observed. An upper limit on the branching fraction of B^{+}→K^{+}νν[over ¯] of 4.1×10^{-5} is set at the 90% confidence level.

Directed evolution of AAV accounting for long-term and enhanced transduction of cardiovascular endothelial cells in vivo.

Cardiac endothelial cells (ECs) are important targets for cardiovascular gene therapy. However, the approach of stably transducing ECs in vivo using different vectors, including adeno-associated virus (AAV), remains unexamined. Regarding this unmet need, two AAV libraries from DNA shuffling and random peptide display were simultaneously screened in a transgenic mouse model. Cardiac ECs were isolated by cell sorting for salvage of EC-targeting AAV. Two AAV variants, i.e., EC71 and EC73, enriched in cardiac EC, were further characterized for their tissue tropism. Both of them demonstrated remarkably enhanced transduction of cardiac ECs and reduced infection of liver ECs in comparison to natural AAVs after intravenous injection. Significantly, persistent transgene expression was maintained in mouse cardiac ECs in vivo for at least 4 months. The EC71 vector was selected for delivery of the endothelial nitric oxide synthase (eNOS) gene into cardiac ECs in a mouse model of myocardial infarction. Enhanced eNOS activity was observed in the mouse heart and lung, which was correlated with partially improved cardiac function. Taken together, two AAV capsids were evolved with more efficient transduction in cardiovascular endothelium in vivo, but their endothelial tropism might need to be further optimized for practical application to cardiac gene therapy.

Wagyu-Angus cross improves meat tenderness compared to Angus cattle but unaffected by mild protein restriction during late gestation.

For the spring-calving beef herds, late gestation coincides with winter and early spring, when cows are dependent on feed supplements with low quality hay, which is hard to meet their nutrient requirements. However, the effects of deficiencies of metabolizable protein intake during late gestation on offspring beef quality are unclear. Wagyu cattle have excellent marbling, and insemination with Wagyu vs Angus semen is a practical option for beef producers to improve beef quality. To test, Angus cows (621 ±â€¯73 kg) were selected and randomly separated into two groups. Each group was inseminated with either Angus or Wagyu semen. During the last 90 days of gestation, cows in each group were further separated and received either a low protein diet (85% of the NRC metabolizable protein requirement), which was a low quality hay-based diet common in northwestern region of the U.S., or an adequate protein diet (108% NRC requirement). All progeny was managed together and harvested at a final BW of 576.5 ±â€¯16.6 kg. Wagyu-sired offspring had higher marbling scores and quality grades than Angus (P < 0.01). Protein supplementation did not affect Slice Shear Force (SSF) in either breeds (P = 0.60). However, Wagyu-sired cattle had lower SSF than Angus-sired (P < 0.01). In addition, Wagyu-sired cattle had higher intramuscular fat (P < 0.05) and total collagen content (P < 0.05), but Angus-sired had greater mature collagen cross-links, as shown by higher contents of Pyridinoline (P < 0.01) and Ehrlich Chromogen (P < 0.01). Consistently, the mRNA expression of enzymes catalyzing collagen cross-linking was higher in Angus-sired offspring, including Plod 1 (P < 0.05), Plod 2 (P = 0.08), and P4Hα 2 (P < 0.01). In conclusion, Wagyu-sired cattle had greater tenderness and marbling score compared to Angus-sired, which was associated with lower collagen cross-links. Feeding mature grass hay-based diet with relatively low protein content during late gestation had no major effect on beef quality of subsequent cattle.

Myosteatosis evaluation using erector spinae and psoas muscles to predict adverse events during adjuvant chemotherapy for breast cancer.

BACKGROUND: Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). METHODS: Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. RESULTS: In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30 kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. CONCLUSION AND RELEVANCE: Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.

[Postoperative complications and their influence on the prognosis factors in gastric cancer patients receiving neoadjuvant treatment].

Objective: To investigate postoperative complications of patients undergoing neoadjuvant therapy followed by radical gastrectomy, and to analyze their influence on the prognosis. Methods: A retrospective case-control study was used. Case inclusion criteria: (1) gastric adenocarcinoma confirmed by histopathology; (2) preoperative imaging examination showed no distant metastasis or peritoneal dissemination; (3) undergoing radical gastrectomy and D2 lymph node dissection after neoadjuvant therapy; (4) complete clinicopathological and follow-up data. According to the above criteria, clinical data of 490 gastric cancer patients who underwent radical gastrectomy in the Cancer Hospital of Chinese Academy of Medical Sciences, Peking Union Medical College from January 2008 to December 2018 were retrospectively collected, including 358 males and 132 females with mean age of (55.0±10.6) years. Neoadjuvant chemotherapy regimens included SOX (S-1+ oxaliplatin, n=151), XELOX (capecitabine+oxaliplatin, n=155), FLOT (docetaxel+oxaliplatin+fluorouracil, n=66), and DOS (docetaxel+ oxaliplatin+S-1, n=68). Preoperative concurrent chemoradiotherapy was performed in 100 patients. SOX regimen was used for 2-4 cycles as induction chemotherapy plus concurrent chemoradiotherapy (3D IMRT+S-1). Postoperative complications were defined as surgery-related complications, mainly including hemorrhage, anastomotic leakage, obstruction, anastomotic stenosis, pulmonary infection, abdominal infection, etc. Postoperative complications were graded according to Clavien-Dindo classification. Log-rank test and Cox regression model were used for univanriate multivariate prognostic analysis, respectively. Results: A total of 101 complications ocaured after operation in 87 (17.8%) patients, including 29 cases of major complications (Clavien-Dindo III to V), and 58 cases of minor complications (Clavien-Dindo I to II). Multivariate analysis showed that age > 65 years (HR=3.077, 95% CI: 1.827-5.184, P<0.001) and total gastrectomy (HR=1.735, 95% CI: 1.069-2.814, P=0.026) were independent risk factors for postoperative complications in patients with gastric cancer undergoing neoadjuvant therapy and radical gastrectomy (both P<0.05). The follow-up period was 0.7 to 131.8 months (median 21.5 months), and the 5-year overall survival rate was 47.4%. The 5-year overall survival rates of the complication group (87 cases) and the non-complication group (403 cases) were 33.2% and 50.9%, respectively (P=0.001). Multivariate analysis showed that age (HR=1.906, 95% CI: 1.248-2.913, P=0.003), ypTNM II to III stage (II stage: HR=5.853, 95% CI: 1.778-19.260, P=0.004; III stage: HR=10.800, 95% CI: 3.411-34.189, P<0.001), surgery time>3.5 h (HR=1.492, 95% CI: 1.095-2.033, P=0.011), total gastrectomy (HR=1.657, 95% CI: 1.216-2.257, P=0.001) and postoperative complications (HR=1.614, 95% CI: 1.125-2.315, P=0.009) were independent risk factors for prognosis, and postoperative adjuvant therapy (HR=0.578, 95% CI: 0.421-0.794, P=0.001) was an independent protective factor for prognosis. Conclusions: The occurrence of postoperative complications in gastric cancer patients undergoing neoadjuvant therapy is closely related to the age of the patients and the range of surgical resection. It is beneficial to improve the prognosis for these patients by paying more attention to the prevention of postoperative complications and the reinforcement of postoperative adjuvant therapy.