Effects of glutamate and aspartate on prostate cancer and breast cancer: a Mendelian randomization study.

BACKGROUND: Respectively, prostate cancer (PCa) and breast cancer (BC) are the second most and most commonly diagnosed cancer in men and women, and they account for a majority of cancer-related deaths world-wide. Cancer cells typically exhibit much-facilitated growth that necessitates upregulated glycolysis and augmented amino acid metabolism, that of glutamine and aspartate in particular, which is tightly coupled with an increased flux of the tricarboxylic acid (TCA) cycle. Epidemiological studies have exploited metabolomics to explore the etiology and found potentially effective biomarkers for early detection or progression of prostate and breast cancers. However, large randomized controlled trials (RCTs) to establish causal associations between amino acid metabolism and prostate and breast cancers have not been reported. OBJECTIVE: Utilizing two-sample Mendelian randomization (MR), we aimed to estimate how genetically predicted glutamate and aspartate levels could impact upon prostate and breast cancers development. METHODS: Single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), associated with the serum levels of glutamate and aspartate were extracted from the publicly available genome-wide association studies (GWASs), which were conducted to associate genetic variations with blood metabolite levels using comprehensive metabolite profiling in 1,960 adults; and the glutamate and aspartate we have chosen were two of 644 metabolites. The summary statistics for the largest and latest GWAS datasets for prostate cancer (61,106 controls and 79,148 cases) were from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium, and datasets for breast cancer (113,789 controls and 133,384 cases) were from Breast Cancer Association Consortium (BCAC). The study was performed through two-sample MR method. RESULTS: Causal estimates were expressed as odds ratios (OR) and 95% confidence interval (CI) per standard deviation increment in serum level of aspartate or glutamate. Aspartate was positively associated with prostate cancer (Effect = 1.043; 95% confidence interval, 1.003 to 1.084; P = 0.034) and breast cancer (Effect = 1.033; 95% confidence interval, 1.004 to 1.063; P = 0.028); however, glutamate was neither associated with prostate cancer nor with breast cancer. The potential causal associations were robust to the sensitivity analysis. CONCLUSIONS: Our study found that the level of serum aspartate could serve as a risk factor that contributed to the development of prostate and breast cancers. Efforts on a detailed description of the underlying biochemical mechanisms would be extremely valuable in early assessment and/or diagnosis, and strategizing clinical intervention, of both cancers.

Predictors for successful sperm retrieval of salvage microdissection testicular sperm extraction (TESE) following failed TESE in nonobstructive azoospermia patients.

The purpose of this study was to observe the clinical utility and the possible determinants in predicting sperm retrieval of salvage microdissection testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA) patients with failed conventional TESE at their first attempts. A total of 52 NOA males underwent salvage mTESE were recruited in this study. Related data, including age, BMI, the presence of Klinefelter's syndrome and varicocele, cryptorchidism, mean testicular volume, hormonal profile (total testosterone (TT), follicle-stimulating hormone (FSH), luteinising hormone (LH), inhibin B (INHB)), testicular histology and surgical duration, were collected and analysed. A multivariate logistic regression with likelihood ratio test revealed the following predictors of sperm retrieval: TT and testicular histology (chi-square of likelihood ratio = 26.42, df = 4, p < .005). A formula was also established using multivariate regression analysis in predicting sperm retrieval probability. A predicted probability of more than 71% was determined of the formula as the cut-off value in predicting sperm retrieval using receiver operating characteristics (ROC) analysis with a sensitivity and specificity 78.0% and 72.4% respectively. In conclusion, salvage mTESE is of clinical value in NOA males with failed TESE attempts, whereas the established formula could be useful in determining the proper salvage mTESE candidates.

Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy.

BACKGROUND: The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. METHODS: A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. RESULTS: Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. CONCLUSION: Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption.

Acute spontaneous neck haematoma in children: a rare entity.

BACKGROUND: Acute spontaneous neck haematoma is rare in children. This rare type of hematoma occurs abruptly without any preceding trauma or iatrogenic damage, making it very difficult to determine the cause precisely. We report here the first two cases of acute spontaneous neck haematoma presenting with neck swelling, and discuss in this article the diagnosis and treatment strategy in our patients. CASE PRESENTATION: We report a 19-month-old girl and a 30 month-old boy with neck swelling for 10 days. There was no history of trauma, cough, excessive muscular strain or iatrogenic injury, and both patients were not on any anticoagulants or antiplatelet drugs. On initial examination, the swelling was tender, firm and not mobile on palpation. A definite diagnosis was made by hematoma puncture. Both of the haematoma resolved spontaneously in two weeks without any complications or sequelae. CONCLUSIONS: Acute spontaneous neck hematoma in children is a rare disorder without any etiology or precipitating factors. The difficulty in making an early diagnosis is mainly due to the nonspecific presenting symptoms. Conservative management and follow-up is recommended as a choice of treatment.

A modified intranasal endoscopic excision for nasal vestibular cyst in China.

This study aimed to improve the surgical removal procedure for nasal vestibular cysts. Twenty-three patients with nasal vestibular cysts underwent surgical removal of the cyst via a transoral sublabial approach and another 30 patients via a modified intranasal endoscopic excision method. The 30 patients were treated with local anesthesia and the roof of the cyst, which was firmly attached to the mucous membrane of the anterior floor of the nasal cavity, was removed transnasally with microdebrider. Bleeding of the opening was stopped by electric coagulation without nasal packing. Among the 30 consecutive patients who underwent the modified surgical procedure, all patients were successfully treated. The mean duration of surgery was 5.7 ± 2.6 min. The mean estimated blood loss was 3.5 ± 2.1 ml. All patients were outpatients. The mean hospital stay was 1 h. The mean total cost was 140. The visual analog scale scores of postoperative pain, pressure and nasal obstruction were 1, 0 and 1, respectively. The incidence rate of postoperative lip swelling or numbness was 0 %. Postoperative endoscopic findings revealed that the cyst was replaced by an air-containing sinus with a persistent opening at the anterolateral nasal floor. There was no recurrence during a mean follow-up of 18 months. The modified intranasal endoscopic excision is a simple, less invasive, low-cost and effective surgical procedure for the treatment of nasal vestibular cysts. It might change the pattern of treatment for nasal vestibular cysts in China.

Investigation of the causal relationship between Interleukin-6 signaling and gastrointestinal tract cancers: A Mendelian randomization study.

BACKGROUND: Observational studies indicate that interleukin-6(IL-6) has been associated with gastrointestinal tract cancers. However, the causal association is still confusing. Thus, we aimed to putative the causality between IL-6 signaling and gastrointestinal tract cancers. METHODS: We conducted a two-sample Mendelian randomization analysis to assess the causal effects. Two groups of IL-6 signaling-related single nucleotide polymorphisms were chosen from two Genome-wide association studies. Summary-level data for gastrointestinal tract cancers including esophageal, gastric, and colorectal cancer, were obtained from the FinnGen consortium and UK Biobank study. We also performed survival analysis to explore the prognostic value of IL-6 in gastrointestinal tract cancers. RESULTS: Genetically predicted plasma sIL6R level, which inhibits IL-6 Signaling, was associated with a reduced risk of gastric cancer in FinnGen. In the combined analysis of the two sources, genetically predicted sIL6R was associated with a decreased risk of gastric cancer (OR = 0.943, 95%CI: 0.904,0.983, p = 0.006). Survival analysis results indicated the prognostic value of IL-6 in gastric cancer. CONCLUSIONS: These results present evidence indicating that genetically-determined reduced IL-6 signaling lowers the risk of gastric cancer, which may provide potential prevention and therapeutic strategies for gastric cancer. Additionally, IL-6 may be a prognostic biomarker for gastric cancer.

Person-centred interventions to improve patient-provider relationships for HIV services in low- and middle-income countries: a systematic review.

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries. METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient-Centeredness by Scholl. We included person-centred interventions aiming to enhance the patient-provider interactions. We included HIV care continuum outcomes and PROs. RESULTS: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient-provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient-led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient-centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. DISCUSSION: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long-term retention or viral suppression. CONCLUSIONS: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation.

MiR-12200-5p Targets Multiple Members of Wnt Signaling Pathway to Inhibit Osteoblast Differentiation and Bone Formation.

BACKGROUND: Osteoporosis is widespread and has become an emerging problem in the elderly. MicroRNAs could affect osteoblast differentiation and further regulate the occurrence of osteoporosis by targeting osteogenic differentiation signaling pathways. Our screening study found that miR-12200-5p simultaneously targeted six important factors within the Wnt signaling pathway (Apc, Tcf4, Tcf7, Wnt3a, Wnt5a, and Lrp6), indicating that miR-12200-5p might function as a strong regulator of this pathway. Since the Wnt pathway exists as one of the most essential pathways for osteogenic differentiation, miR-12200-5p may have an important role in the development of osteoporosis. OBJECTIVE: This study intended to explore the regulatory role and corresponding mechanism of miR-12200-5p in osteoblast differentiation. METHODS: We investigated the differentiation of osteoblast after the treatments of miR-12200-5p mimic and inhibitor. The interactions between miR-12200-5p and its target genes were also detected. Furthermore, the rescue effect of miR-12200-5p inhibitor on osteoporosis was evaluated using an ovariectomized osteoporosis mouse model. RESULTS: MiR-12200-5p significantly inhibited osteoblast differentiation, and bound with the 3'-UTR sequences of its target genes (Apc, Tcf4, Tcf7, Wnt3a, Wnt5a, and Lrp6) to reduce the expressions of these genes. The inhibition of miR-12200-5p would almost fully alleviate postmenopausal osteoporosis. CONCLUSION: MiR-12200-5p could strongly repress osteoblast differentiation and bone formation by targeting multiple members of the Wnt signaling pathway simultaneously. The study supplemented the theoretical and experimental basis for researching the mechanism of osteogenic differentiation and inspired the development of novel therapeutic strategies for osteoporosis.

DNAJB4 suppresses breast cancer progression and promotes tumor immunity by regulating the Hippo signaling pathway.

PURPOSE: Breast cancer is the most common cancer worldwide. Low DNAJB4 expression levels are strongly correlated with poor prognosis in breast cancer patients. However, the molecular mechanism by which DNAJB4 regulates breast cancer progression is unclear. METHODS: The expression of DNAJB4 was validated in human breast cancer tissues, normal human breast tissues, and breast cancer cell lines. CCK-8, colony-forming, and wound healing assays were used to assess the biological effect of DNAJB4 overexpression on cell proliferation and migration in MCF-7 cell lines. Bioinformatic analysis was used to identify the DNAJB4 related pathways in breast cancer. Epithelial-mesenchymal transition (EMT)-related biomarkers and Hippo pathway components were quantified by Western blots. Luciferase and Western blot assays were used to validate which miRNA regulates DNAJB4. In addition, the effects of DNAJB4 on in vivo tumor growth were assessed in xenograft models. RESULTS: DNAJB4 was expressed at low levels in human breast cancer tissues and breast cancer cell lines and correlated with poor prognosis. DNAJB4 overexpression significantly inhibited cell proliferation and migration in vitro by activating the Hippo pathway. The dual-luciferase assay showed that hsa-miR-183-5p targeted DNAJB4. Moreover, the effects of DNAJB4 could be reversed by miR-183-5p. In addition, the expression of DNAJB4 was strongly correlated with immune infiltration levels. Notably, DNAJB4 overexpression markedly enhanced CD4 + and CD8 + T cells and reduced PD-L1 levels in 4T1 tumors via the Hippo pathway, which retarded tumor growth in a subcutaneous xenograft tumor mouse model of 4T1 cells. CONCLUSIONS: The present study demonstrated that DNAJB4 overexpression inhibited the malignant biological behavior of breast cancer by regulating the Hippo pathway and tumor immunosuppressive environment.

A potential therapeutic drug for osteoporosis: prospect for osteogenic LncRNAs.

Long non-coding RNAs (LncRNAs) play essential roles in multiple physiological processes including bone formation. Investigators have revealed that LncRNAs regulated bone formation through various signaling pathways and micro RNAs (miRNAs). However, several problems exist in current research studies on osteogenic LncRNAs, including sophisticated techniques, high cost for in vivo experiment, as well as low homology of LncRNAs between animal model and human, which hindered translational medicine research. Moreover, compared with gene editing, LncRNAs would only lead to inhibition of target genes rather than completely knocking them out. As the studies on osteogenic LncRNA gradually proceed, some of these problems have turned osteogenic LncRNA research studies into slump. This review described some new techniques and innovative ideas to address these problems. Although investigations on osteogenic LncRNAs still have obtacles to overcome, LncRNA will work as a promising therapeutic drug for osteoporosis in the near future.

A GSTP1-mediated lactic acid signaling promotes tumorigenesis through the PPP oxidative branch.

Lactic acidosis is a feature of solid tumors and plays fundamental role(s) rendering cancer cells to adapt to diverse metabolic stresses, but the mechanism underlying its roles in redox homeostasis remains elusive. Here we show that G6PD is phosphorylated at tyrosine 249/322 by the SRC through the formation of a GSTP1-G6PD-SRC complex. Lactic acid attenuates this formation and the phosphorylation of G6PD by non-covalently binding with GSTP1. Furthermore, lactic acid increases the activity of G6PD and facilitates the PPP (NADPH production) through its sensor GSTP1, thereby exhibiting resistance to reactive oxygen species when glucose is scarce. Abrogating a GSTP1-mediated lactic acid signaling showed attenuated tumor growth and reduced resistance to ROS in breast cancer cells. Importantly, positive correlations between immuno-enriched SRC protein and G6PD Y249/322 phosphorylation specifically manifest in ER/PR positive or HER negative types of breast cancer. Taken together, these results suggest that GSTP1 plays a key role in tumor development by functioning as a novel lactate sensor.

Beyond RuBisCO: convergent molecular evolution of multiple chloroplast genes in C4 plants.

BACKGROUND: The recurrent evolution of the C4 photosynthetic pathway in angiosperms represents one of the most extraordinary examples of convergent evolution of a complex trait. Comparative genomic analyses have unveiled some of the molecular changes associated with the C4 pathway. For instance, several key enzymes involved in the transition from C3 to C4 photosynthesis have been found to share convergent amino acid replacements along C4 lineages. However, the extent of convergent replacements potentially associated with the emergence of C4 plants remains to be fully assessed. Here, we conducted an organelle-wide analysis to determine if convergent evolution occurred in multiple chloroplast proteins beside the well-known case of the large RuBisCO subunit encoded by the chloroplast gene rbcL. METHODS: Our study was based on the comparative analysis of 43 C4 and 21 C3 grass species belonging to the PACMAD clade, a focal taxonomic group in many investigations of C4 evolution. We first used protein sequences of 67 orthologous chloroplast genes to build an accurate phylogeny of these species. Then, we inferred amino acid replacements along 13 C4 lineages and 9 C3 lineages using reconstructed protein sequences of their reference branches, corresponding to the branches containing the most recent common ancestors of C4-only clades and C3-only clades. Pairwise comparisons between reference branches allowed us to identify both convergent and non-convergent amino acid replacements between C4:C4, C3:C3 and C3:C4 lineages. RESULTS: The reconstructed phylogenetic tree of 64 PACMAD grasses was characterized by strong supports in all nodes used for analyses of convergence. We identified 217 convergent replacements and 201 non-convergent replacements in 45/67 chloroplast proteins in both C4 and C3 reference branches. C4:C4 branches showed higher levels of convergent replacements than C3:C3 and C3:C4 branches. Furthermore, we found that more proteins shared unique convergent replacements in C4 lineages, with both RbcL and RpoC1 (the RNA polymerase beta' subunit 1) showing a significantly higher convergent/non-convergent replacements ratio in C4 branches. Notably, more C4:C4 reference branches showed higher numbers of convergent vs. non-convergent replacements than C3:C3 and C3:C4 branches. Our results suggest that, in the PACMAD clade, C4 grasses experienced higher levels of molecular convergence than C3 species across multiple chloroplast genes. These findings have important implications for our understanding of the evolution of the C4 photosynthesis pathway.

Circulating fatty acids and risk of primary open-angle glaucoma: A mendelian randomization study.

PURPOSE: The relationship between fatty acids (FAs) and glaucoma remains controversial despite several observational studies. We organized a mendelian randomization (MR) study to determine the genetic causal association between circulating FAs and primary open-angle glaucoma (POAG). METHODS: The two-sample MR method was used to acquire causal estimates. Fourteen distinct single nucleotide polymorphisms (SNPs) of ten FAs were chosen as instrumental variables (IVs) at a genome-wide significance level (p < 5 × 10-8). Summary statistics for POAG were available from a genome-wide association meta-analysis of 216,257 individuals of European ancestry (16,677 cases, 199,580 controls). The inverse-variance weighted (IVW) method was adopted to evaluate the causality of FAs and POAG. Multiple sensitivity analyses were applied to avoid pleiotropy. RESULTS: The IVW method suggested no evidence to support causal effects of ten FAs on POAG. The odds ratio (OR) per one SD increment of each FA was ORALA = 1.64 (95% CI, 0.441-6.098, p = 0.46), OREPA = 0.815 (95% CI, 0.604-1.101, p = 0.182), ORDPA = 0.896 (95% CI, 0.669-1.198, p = 0.458), ORDHA = 1.014 (95% CI, 0.801-1.283, p = 0.91), ORLA = 1.008 (95% CI, 0.971-1.045, p = 0.683), ORAA = 0.993 (95% CI, 0.973-1.013, p = 0.483), ORPOA = 0.731 (95% CI, 0.261-2.048, p = 0.551), OROA = 1.048 (95% CI, 0.934-1.175, p = 0.425), ORPA = 1.039 (95% CI, 0.903-1.196, p = 0.593), ORSA = 0.967 (95% CI, 0.879-1.062, p = 0.477). Moreover, Sensitivity analysis indicated no pleiotropy. CONCLUSION: This MR study does not support causal associations between ten FAs and POAG.

Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study.

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study. Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above. Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method. Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis. Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.

Therapeutic values of chick early amniotic fluid (ceAF) that facilitates wound healing via potentiating a SASP-mediated transient senescence.

Inflammatory, proliferative and remodeling phases constitute a cutaneous wound healing program. Therapeutic applications and medication are available; however, they commonly are comprised of fortified preservatives that might prolong the healing process. Chick early amniotic fluids (ceAF) contain native therapeutic factors with balanced chemokines, cytokines and growth-related factors; their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development. Instead, they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions. Employing both in vitro and in vivo models, we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence, known to be intimately intermingled with Senescence Associated Secretory Phenotypes (SASP) that function in addition to or in conjunction with ceAF to facilitate wound healing. In our cutaneous wound healing models, a low dose of ceAF exhibited the best efficacies; however, higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold. Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing, suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence, expediting cellular proliferation, migration, and describing a homeostatic and balanced dosage strategy in medical intervention.

Treatment of recurrent head and neck carcinoma involving the carotid artery: carotid reconstruction with ePTFE graft.

The aim of our study is to investigate the feasibility of reconstructing the carotid artery using expanded polytetraflouroethylene (ePTFE) in patients with recurrent head and neck carcinoma involving the carotid artery. Ten patients, who had recurrent head and neck carcinoma involving the carotid artery, received carotid artery resection and reconstruction with ePTFE, tissue defects were repaired by pectoralis major myocutaneous flap. Results show that eight patients did not present any vascular and neurologic complications. One patient presented slight hemiparesis, another patient developed wound infection and pharyngocutaneous fistula. The mean follow-up period was 33.1 ± 16.0 months. The 2-year survival rate was 50% (5/10), and there was one patient who survived for 60 months without locoreginal recurrence or distant metastasis. En bloc resection of tumor and involved carotid-associated ePTFE reconstruction provide effective improvement in the locoregional control of the recurrent head and neck carcinoma. The pedicle pectoralis major myocutaneous flap can provide not only wound bed with affluent blood supply for the vascular grafts, but also reparation of skin or the tissue defects of oropharynx and hypopharynx.

Lubricants for the promotion of sexual health and well-being: a systematic review.

AbstractPromoting sexual health is a World Health Organization (WHO) priority. Lubricants are widely available and used to improve sexual pleasure and reduce pain during intercourse. To inform WHO's self-care interventions guideline, we conducted a systematic review of the peer-reviewed literature to answer the question: does use of lubricants during or prior to sex result in improved sexual health and well-being. We searched PubMed, CINAHL, LILACS and EMBASE on 8 July 2020 for effectiveness, values and preferences, and cost data related to commercially available vaginal and anal lubricants. Data were systematically extracted and qualitatively synthesised. Effectiveness evidence was summarised in GRADE evidence profiles. Seven studies met the effectiveness review criteria. Two randomised trials found lubricant use led to improved female sexual well-being and had no impact on incidence of human papillomavirus (moderate certainty evidence). One observational study with gay and bisexual men showed lubricants were associated with increased reports of pain during receptive intercourse and no difference in pain during insertive intercourse, but a reduced degree of pain in both types of intercourse (low/very low certainty evidence). One observational study with female breast cancer survivors found better outcomes of vaginal dryness and dyspareunia with lubricant use (very low certainty evidence). Twenty-one values and preferences studies from diverse populations globally found that most individuals supported lubricant use for reasons of comfort/reduced pain and sexual pleasure. No cost studies were identified. Although evidence is limited, lubricants appear to offer an acceptable approach to improving sexual health and well-being.

Causal Associations between Serum Urea and Cancer: A Mendelian Randomization Study.

Urea is largely derived from the urea cycle reactions through hepatic detoxification of free ammonia and cleared by urination, and the serum urea level is a crucial medical indicator for measuring the kidney function in patients with nephropathy; however, investigative revelations pointing to the serum urea level as a risk factor for cancer are very scarce, and relevant studies are restricted by potential biases. We aimed to explore the causal relationships of the serum urea level with cancer development by focusing on renal cell carcinoma (RCC) using the Mendelian randomization (MR) analyses. Summary estimates were collected from the inverse-variance weighted (IVW) method based on six single nucleotide polymorphisms (SNPs). The selected SNPs related to the serum urea were obtained from a large genome-wide association study (GWAS) of 13,312 European participants. The summary statistics of RCC were also available from public databases (IARC, n = 5219 cases, n = 8011 controls). Sensitivity analyses included the weighted median and MR-Egger methods. Serum urea was inversely associated with RCC in females (effect = 1.93; 95% CI: 1.24 to 3.01; p = 0.004) but exhibited null association with RCC in males, breast cancer (BRCA) in both genders and prostate cancer (PCa) in males. Similar conclusions were also drawn from the weighted median and MR-Egger. These findings reveal an intriguing link between serum urea and cancer risks for the very first time. Without ambiguity, the serum urea is causatively related to RCC specifically in females, although the mechanism(s) by which urea is involved in RCC development remains to be experimentally/clinically investigated. Our studies may well provide novel insights for RCC diagnosis, intervention and/or therapy.

Using Genetic Variants to Evaluate the Causal Effect of Plasma Phospholipid Fatty Acids on Breast Cancer and Prostate Cancer: A Mendelian Randomization Study.

BACKGROUND: Observational studies indicate that phospholipid fatty acids (FAs) have an impact on the etiology in cancers, but the results are conflicting. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer. METHODS: Fourteen single nucleotide polymorphisms (SNPs) were selected as instrumental variables to predict the level of 10 phospholipid FAs from Genome-wide association studies (GWAS). We obtained the summary statistics for the latest and largest GWAS datasets for breast cancer (113,789 controls and 133,384 cases) and prostate cancer (61,106 controls and 79,148 cases) from the Breast Cancer Association Consortium (BCAC) and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Two-sample Mendelian randomization analysis was applied. RESULTS: The results demonstrate that the 10 individual plasma phospholipid FAs are not significantly associated with breast cancer risk and prostate cancer risk. CONCLUSION: The evidence is insufficient to support the causal association of the 10 individual plasma phospholipid FAs with breast cancer and prostate cancer.

Extensive Variation in Drought-Induced Gene Expression Changes Between Loblolly Pine Genotypes.

Drought response is coordinated through expression changes in a large suite of genes. Interspecific variation in this response is common and associated with drought-tolerant and -sensitive genotypes. The extent to which different genetic networks orchestrate the adjustments to water deficit in tolerant and sensitive genotypes has not been fully elucidated, particularly in non-model or woody plants. Differential expression analysis via RNA-seq was evaluated in root tissue exposed to simulated drought conditions in two loblolly pine (Pinus taeda L.) clones with contrasting tolerance to drought. Loblolly pine is the prevalent conifer in southeastern U.S. and a major commercial forestry species worldwide. Significant changes in gene expression levels were found in more than 4,000 transcripts [drought-related transcripts (DRTs)]. Genotype by environment (GxE) interactions were prevalent, suggesting that different cohorts of genes are influenced by drought conditions in the tolerant vs. sensitive genotypes. Functional annotation categories and metabolic pathways associated with DRTs showed higher levels of overlap between clones, with the notable exception of GO categories in upregulated DRTs. Conversely, both differentially expressed transcription factors (TFs) and TF families were largely different between clones. Our results indicate that the response of a drought-tolerant loblolly pine genotype vs. a sensitive genotype to water limitation is remarkably different on a gene-by-gene level, although it involves similar genetic networks. Upregulated transcripts under drought conditions represent the most diverging component between genotypes, which might depend on the activation and repression of substantially different groups of TFs.