IGFBP7 promotes gastric cancer by facilitating epithelial-mesenchymal transition of gastric cells.

Gastric cancer (GC) with high morbidity and mortality is one major cause of tumor-related death. Mechanisms underlying GC invasion and metastasis remain unclear. IGFBP7 exerted variable effects in different cancers and its role in GC is controversial. Here, IGFBP7 was found to be upregulated and elevated IGFBP7 expression represented a poorer overall survival in GC using bioinformatics analysis. Moreover, IGFBP7 was up-regulated in human GC specimens and promoted tumor growth in xenograft tumor animals. For GC cell lines, we found that IGFBP7 was also upregulated and facilitated the cell malignant behavior and EMT of GC cells, which may involve NF-κB and ERK signaling pathways. This research may provide new avenues for GC therapy.

Prevalence and correlates of mental health problems among different occupations of medical workers during COVID-19 outbreak in China.

Background: Health workers involved in the fight to prevent the COVID-19 outbreak were exposed to hazards. Detailed information on mental health problems in different medical occupations is crucial. To examined the prevalence of mental health issues in three medical occupations as well as the relationships between mental health problems and correlates in each occupation. Methods: This study utilizing the Questionnaire Star program was conducted among medical workers working at medical institutions in China from February 17 to 24, 2020. The Self-Reporting Questionnaire (SRQ-20), the Zung Self-rating Anxiety Scale (SAS), and the Zung Self-rating Depression Scale (SDS) were used to assess mental health problems. Results: The prevalence of any mental health problems in the three occupations was 43.6, 34.6, and 32.9% for nurses, paramedical workers (PMWs), and doctors, respectively. Three occupations shared some correlates, such as being overworked, not having enough time to rest, support from colleagues, and previous mental health status. There were specific factors for each occupation. For doctors, age, educational level, living status, support from family, and previous physical status were related factors in mental health problems. Working in a designated hospital for treating COVID-19, having COVID-19 event exposures, and receiving support from family were associated with the mental health problems of the nurses. PMWs' mental health problems was linked to educational level and care from supervisors or heads of department. Conclusion: Different medical occupations have distinct impacts on mental health issues. Policy makers and mental health professionals working to prepare for potential disease outbreaks should be aware of multiple factors in different occupations.

Two chromosome-level genome assemblies of Rhodiola shed new light on genome evolution in rapid radiation and evolution of the biosynthetic pathway of salidroside.

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.

The Role of Smoking, Obesity, and Physical Inactivity in Cognitive Performance and Decline: A Multicohort Study.

BACKGROUND: Unhealthy lifestyles are recognized contributors to cognitive decline, yet limited evidence focuses on their roles in cognitive decline rate. This study examined the role of smoking, obesity, and physical inactivity in cognitive performance and rate of cognitive decline by birth cohort on a global scale. METHODS: Utilizing data from 4 prospective cohort studies (China Health and Retirement Longitudinal Study, English Longitudinal Study on Ageing, Health and Retirement Study, and Survey of Health, Ageing and Retirement in Europe) across 14 countries, a multicohort study was performed. Eligible participants were aged 50 years and older. Linear mixed models were employed to detect the role of smoking, obesity, and physical inactivity in cognitive function domains (epidemic memory, working memory, and time orientation). RESULTS: Higher scores of cognitive functions were found in participants who engaged in more vigorous physical activity, were noncurrent smokers, and maintained underweight (eg, for episodic memory scores in females at 60 years, vigorous physical activity: 0.47, 95% CI: 0.46, 0.49). In addition, a slower rate of cognitive decline was also found in individuals who engaged in moderate or vigorous physical activity, were noncurrent smokers, and maintained not being underweight (eg, for episodic memory scores changing from 50 to 70 years old in females, vigorous physical activity: from 0.54 (95% CI: 0.51, 0.57) to 0.40 (95% CI: 0.37, 0.44) and in males from 0.33 (95% CI: 0.30, 0.36) to 0.11 (95% CI: 0.08, 0.14). CONCLUSIONS: We confirmed the beneficial impact of healthy lifestyles in preventing cognitive decline and promoting healthy aging. Urgent measures are needed to identify and encourage healthy lifestyles, such as strengthening tobacco control, developing policy on physical activity promotion, and preventing underweight, to minimize worldwide levels of cognitive decline.

Associations of adverse childhood experiences with common psychiatric disorder in later life: results from the China mental health survey.

BACKGROUND: Associations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China. METHODS: The study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders. RESULTS: Prevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant. CONCLUSIONS: ACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults' mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Endothelial-Related Biomarkers in Evaluation of Vascular Function During Progression of Sepsis After Severe Trauma: New Potential Diagnostic Tools in Sepsis.

Purpose: This study aimed to investigate the changes in endothelial-related biomarkers and their relationship with the incidence and prognosis of patients with sepsis after severe trauma. Methods: A total of 37 severe trauma patients admitted to our hospital from Jan. to Dec. 2020 were enrolled in our research. All enrolled patients were divided into the sepsis and the non-sepsis groups. Endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were detected on admission time; 24-48 hours and 48-72 hours after admission respectively. Demographic data, Acute Physiology, Chronic Health Evaluation (APACHE) II, and Sequential Organ Failure Assessment (SOFA) score were calculated every 24 h of admission to assess the severity of organ dysfunction. Receiver operating characteristic (ROC) curves were drawn to compare the areas under the curve (AUC) of endothelial-related biomarkers for the diagnosis of sepsis. Results: The incidence rate of sepsis was 45.95% in all patients. The SOFA score in the sepsis group was significantly higher than that in the non-sepsis group (2 points vs 0 points, P<0.01). The number of EPCs, CECs, and EMPs all rose quickly in the early phase after trauma. The number of EPCs was similar in both groups, but the number of CECs and EMPs in the Sepsis Group was much higher than in the non-Sepsis Group (all P<0.01). Logistic regression analysis showed that the occurrence of sepsis was closely related to the expression of 0-24h CECs and 0-24h EMPs. The AUC ROC for CECs in different time periods were 0.815, 0.877, and 0.882, respectively (all P<0.001). The AUC ROC for EMPs in 0-24h was 0.868 (P=0.005). Conclusion: The expression of EMPs was higher in early severe trauma, and high levels of EMPs were significantly higher in patients with early sepsis and poor prognosis.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

Anti-CD47 Antibody Enhances the Efficacy of Chemotherapy in Patients with Gastric Cancer Liver Metastasis.

Patients with gastric cancer liver metastasis (GCLM) are often treated with palliative care, and they show a poor prognosis. In gastric cancer, high CD47 expression has been shown to indicate a poor prognosis. CD47, expressed on the cell surface, prevents the cells from being phagocytosed by macrophages. Anti-CD47 antibodies have been shown to be effective in the treatment of metastatic leiomyosarcoma. Nonetheless, the role of CD47 in GCLM has not yet been elucidated. Here, we showed that CD47 expression in GCLM tissues was higher than that in situ. Moreover, we demonstrated that high CD47 expression correlated with an adverse prognosis. Accordingly, we investigated the role of CD47 in the development of GCLM in mouse liver. Knockdown of CD47 inhibited GCLM development. Furthermore, in vitro engulfment assays showed that decreased CD47 expression led to an increased phagocytic activity of Kupffer cells (KCs). Using enzyme-linked immunosorbent assay, we determined that CD47 knockdown promoted cytokine secretion by macrophages. Furthermore, we found that tumor-derived exosomes decreased KC-mediated phagocytosis of gastric cancer cells. Finally, in a heterotopic xenograft model, the administration of anti-CD47 antibodies inhibited tumor growth. In addition, as 5-fluorouracil (5-Fu)-based chemotherapy is the cornerstone in GCLM treatment, we administered a combination of anti-CD47 antibodies and 5-Fu, which acted synergistically to suppress the tumor. Overall, we demonstrated that tumor-derived exosomes are involved in GCLM progression, targeting CD47 inhibits gastric cancer tumorigenesis, and a combination of anti-CD47 antibodies and 5-Fu shows potential for treating GCLM.

Group V Chitin Deacetylases Influence the Structure and Composition of the Midgut of Beet Armyworm, Spodoptera exigua.

Chitin deacetylase (CDA) can accelerate the conversion of chitin to chitosan, influencing the mechanical properties and permeability of the cuticle structures and the peritrophic membrane (PM) in insects. Putative Group V CDAs SeCDA6/7/8/9 (SeCDAs) were identified and characterized from beet armyworm Spodoptera exigua larvae. The cDNAs of SeCDAs contained open reading frames of 1164 bp, 1137 bp, 1158 bp and 1152 bp, respectively. The deduced protein sequences showed that SeCDAs are synthesized as preproteins of 387, 378, 385 and 383 amino acid residues, respectively. It was revealed via spatiotemporal expression analysis that SeCDAs were more abundant in the anterior region of the midgut. The SeCDAs were down-regulated after treatment with 20-hydroxyecdysone (20E). After treatment with a juvenile hormone analog (JHA), the expression of SeCDA6 and SeCDA8 was down-regulated; in contrast, the expression of SeCDA7 and SeCDA9 was up-regulated. After silencing SeCDAV (the conserved sequences of Group V CDAs) via RNA interference (RNAi), the layer of intestinal wall cells in the midgut became more compact and more evenly distributed. The vesicles in the midgut were small and more fragmented or disappeared after SeCDAs were silenced. Additionally, the PM structure was scarce, and the chitin microfilament structure was loose and chaotic. It was indicated in all of the above results that Group V CDAs are essential for the growth and structuring of the intestinal wall cell layer in the midgut of S. exigua. Additionally, the midgut tissue and the PM structure and composition were affected by Group V CDAs.

Improve the dupilumab therapy evaluation with dermoscopy and high-frequency ultrasound in moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease. Monoclonal antibody dupilumab was approved to treat moderate-to-severe AD in recent years. An objective assessment of treatment response by skin imaging modality is adjuvant for clinical evaluations. This study aimed to explore the value of dermoscopy and high-frequency ultrasound (HFUS) imaging characteristics in treatment evaluation for moderate-to-severe AD patients treated with dupilumab. METHODS: Moderate-to-severe AD patients refractory to conventional therapy were enrolled in the study. All patients went through at least a 16-week standardized treatment of dupilumab. Clinical scores (eczema area scoring index [EASI], SCOARD, numerical rating scale of pruritus, dermatology life quality index), dermoscopy, and HFUS examinations were conducted at 0, 2, 4, 8, 12, and 16 weeks of treatment. Erythema, scales, erosion, and pigmentation under dermoscopy were scored, and subepidermal low-echogenic band (SLEB) thickness under HFUS was measured as quantitative indexes. Descriptive analysis and mixed effect linear regression models were used for statistical analysis. RESULTS: Sixteen patients were enrolled in the study and their average age was 45.63 ± 18.18 years. All clinical scores decreased with significant difference after 16-week treatment compared with baseline. All patients achieved EASI 50 (EASI score decreased by 50% or more), and 9/16 patients reached EASI 75 after 16-week treatment. Dermoscopy evaluation of erythema, scales and erosion scores were decreased, and the sign of pigmentation score was increased after treatment. For HFUS, the mean SLEB value was 0.51 ± 0.29 mm and decreased to 0.27 ± 0.15 mm after 16-week treatment (p < 0.01). SLEB value decreased linearly with treatment time and correlated with clinical scores. However, SLEB values of two patients were 0.57 and 0.68 mm at week 16, respectively, which were higher than the average, and one of the patients showed EASI 75. CONCLUSION: Dermoscopy and HFUS were able to reveal deeper inflammation response than clinical scores in AD and can be an effective method to evaluate and monitor clinical improvement during dupilumab treatment for AD patients. The preliminary value of imaging methods for predicting the treatment endpoint of dupilumab remains to be verified.

Long-term anxiety and depression signatures of participants that received esophageal cancer screening: A multicenter population-based cohort study.

BACKGROUND: Current evidence on the psychological impact of screening and diagnosis of esophageal cancer (EC) is limited and unclear. METHODS: This multicenter, population-based, prospective study was conducted in five high-incidence regions in China from 2017 to 2020. The screened participants were diagnosed as healthy, esophagitis, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), or EC based on pathological biopsy. The psychological impact of the screening was assessed by comparing anxiety and depression symptoms at baseline and follow-up. RESULTS: A total of 1973 individuals were ultimately included, with an average follow-up of 22.2 months. The prevalence of anxiety and depression symptoms in screened population at baseline was 14.3% and 18.4%. The prevalence of anxiety and depression symptoms of screeners at follow-up declined (all p < 0.001). The anxiety (RR [95% CI]: 0.37 [0.30-0.46]) and depression (0.29 [0.24-0.36]) of screeners weakened over time, but the anxiety and depression symptoms was continuous for patients with HGIN and patients with EC. Compared with the participants classified as normal, the RRs(95% CI) of anxiety and depression symptoms were 2.20 (1.10-4.30) and 2.03 (1.07-3.86) for the patients with HGIN and 2.30 (0.82-6.20) and 3.79 (01.71-8.43) for the patients with EC. CONCLUSION: The anxiety and depression symptoms of screeners weakened over time, except in patients with HGIN and EC, for whom it remained lasting and high. Psychological assistance and interventions are urgently needed for individuals who are ready for screening and for those diagnosed as having HGIN or EC.

Influence of PCDH9 (rs9540720) and narcissistic personality traits on the incidence of major depressive disorder in Chinese first-year university students: findings from a 2-year cohort study.

Objective: The objective of this study was to explore the influence of the polymorphism of the protocadherin 9 (PCDH9) gene and the narcissistic personality trait (NPT) on the risk of major depressive disorder (MDD) in Chinese first-year university students. Methods: A 2-year cohort study was conducted among Chinese first-year university students who were enrolled in 2018 from two universities in Shandong Province, China. The snapshot technique was used to detect the genotypes of PCDH9 (rs9540720). The Chinese version of the Composite International Diagnostic Interview was used for the MDD assessment. The NPTs were measured by 11 items based on DSM-IV. Patient Health Questionnaire-9 and the Beck Anxiety Inventory were used to assess depressive and anxiety symptoms, respectively. Logistic regression modeling was carried out to examine the relationship between rs9540720, NPTs, and the incidence of MDD. Results: A total of 5,327 students participated in the baseline and follow-up studies and provided their blood samples. PCDH9 (rs9540720) (ORGG+GA = 2.33, 95% CI: 1.35-4.02) and NPTs (OR5-9 = 2.26, 95% CI: 1.40-3.64) increased the risk of MDD onset. There was no multiplicative interaction between NPTs and Rs9540720 (OR = 1.51, 95% CI: 0.30-7.63). Furthermore, there was no additive interaction between them (RERI = 2.40, 95% CI: -0.82-5.62; AP = 0.47, 95% CI: -0.04-0.97; and S = 2.37, 95% CI: 0.54-10.33). Conclusion: PCDH9 (rs9540720) and more NPTs are the risk factors for the incidence of MDD in Chinese first-year university students.

Identification and functional analysis of two potential RNAi targets for chitin degradation in Holotrichia parallela Motschulsky (Insecta Coleoptera).

Chitin metabolism enzymes are safe and desirable targets for pest management. ß-N-acetylglucosaminidase (NAG) and N-acetylglucosamine kinase (NAGK) are involved in chitin degradation. NAG is the main glycosidase that works synergistically with chitinases. NAGK is a key enzyme for the generation of UDP-Nacetylglucosamine (UDP-GlcNAc) and for the conversion of GlcNAc into GlcNAc 6-phosphate (GlcNAc-6-P). In this study, NAG and NAGK genes were identified from Holotrichia parallela, a polyphagous soil pest that causes serious damage to crops. The spatiotemporal expression investigated by RT-qPCR indicated that the two genes are expressed in all larval developmental stages. HpNAG is highly expressed in the integument and HpNAGK overexpressed in the midgut. After injection of dsHpNAG and dsHpNAGK, a significant RNAi effect was found after 72 h and larvae stopped growing. The survival rates of larvae were 13.3% and 16.7%, respectively. RNAi of HpNAG and HpNAGK regulated the expression levels of chitin metabolism-related genes, indicating that these two genes could be critical in the chitin metabolism. Furthermore, silencing HpNAG and HpNAGK reduced the thickness of the cuticle, and decreased its content of chitin. The study will lay a foundation for further clarifying the mechanism of chitin metabolism and provide potential targets for the biological control of H. parallela larvae.

Long-term disability in common mental disorders in Chinese community: evidence from a five-year follow-up study.

BACKGROUND: Common mental disorders are general term for mental disorders with high disability rates and significant social burden. The purpose of this study was to determine the degree of long-term disability associated with common mental disorders and to interpret the relationship between common mental disorders and long-term disability. METHODS: Participants in the 2013 China Mental Health Survey were followed up by telephone between April and June 2018. This study evaluated long-term disability over a five-year period using the World Health Organization's Disability Assessment Schedule 2.0. Poisson regression was used to analyze the relationship between common mental disorders and long-term disability. RESULTS: A total of 6269 patients were followed up by telephone. In patients with common mental disorders, the prevalence of disability ranged from 7.62% to 43.94%. The long-term disabilities were significantly associated with dysthymic disorder (DD, RR:2.40; 95% CI:1.87-3.03), major depressive disorder (MDD, RR:1.63; 95% CI:1.34-1.98), generalized anxiety disorder (GAD, RR:1.95; 95% CI:1.15-3.09), obsessive-compulsive disorder (OCD, RR:1.68; 95% CI:1.24-2.22) and alcohol use disorder (AUD, RR: 1.42; 95% CI:0.99-1.96). CONCLUSIONS: In China, common mental disorders raise the risk of long-term disability, and there is a critical need for monitoring patients with DD, MDD, GAD, OCD, and AUD. For improved quality of life and reduced disability levels, more resources need to be dedicated to mental health in the future.

The psychological impact of esophageal cancer screening on anxiety and depression in China.

Objective: The psychological impact of screening is unclear and has been ignored. This study aimed to evaluate the psychological impact of esophageal cancer (EC) screening on anxiety and depression in China. Materials and methods: A multicenter, population-based study in five high-risk regions of EC was conducted from 2019 to 2020. Residents were recruited and underwent endoscopic screening and then were diagnosed with normal, esophagitis, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and EC. Subjects who did not participate in the screening were referred to as the control group. We surveyed their anxiety and depression levels at baseline and after endoscopy and informed them of different pathological results to evaluate the psychological impact of the screening process. Results: A total of 2,337 subjects completed all surveys in the screening process (normal: 355, esophagitis: 1,713, LGIN: 213, HGIN: 43 and EC: 13), with 63 controls. The levels of anxiety and depression of screeners were significantly higher than those of controls (P < 0.001). The fluctuation of anxiety and depression showed a "V" pattern in the screening process. The prevalence of anxiety symptoms at baseline, after endoscopy and after knowing the pathological results was 5.6, 0.3, and 3.2%, respectively (P < 0.001), and the corresponding prevalence of depression was 3.6, 0.2, and 2.1%, respectively (P < 0.001). With the aggravation of pathological results, the levels of anxiety and depression increased significantly (P < 0.001), especially in patients informed of HGIN (16.3 and 9.3%) and EC (23.1 and 30.8%). Conclusion: Participation in endoscopic screening may bring short-term adverse psychological effects, especially at baseline and knowing the pathological results. More attention should be given to participants waiting for endoscopic screening. The method of informing the screening results of HGIN and EC should be improved. Further precise screening is needed to concentrate on high-risk groups to reduce the psychological impact of screening.

Value of high-frequency ultrasound in the treatment of moderate and severe acne vulgaris.

BACKGROUND: Acne treatment may fail or cause undesirable side effects due to inaccurate evaluation. High-frequency ultrasound (HFUS) can monitor systemic treatment in patients with moderate-to-severe acne vulgaris. MATERIALS AND METHODS: In this prospective study, consecutive patients with moderate-to-severe acne vulgaris were recruited. Patients were graded by a comprehensive clinical assessment before and after therapy. Simultaneous HFUS grading was independently evaluated according to the sonographic scoring system for acne (SSSA). Clinical and HFUS grades were compared through kappa analysis. RESULTS: A total of 70 patients were enrolled. At baseline, 36 (51.4%) and 34 (48.6%) patients were graded as moderate and severe, respectively, through clinical assessment. However, 27 patients (38.6%) scored SSSA-Grade II and 43 (61.4%) scored SSSA-Grade III in the HFUS grading. Sixty-one patients (87.1%) were in the consistent category as per clinical assessment and HFUS grades, with Kappa1  = 0.745, whereas higher HFUS grades were observed in nine patients. By the end of the observation, 65 of all patients (92.9%) showed significant improvement and 5 (7.1%) showed no apparent improvement after the treatment. According to the clinical assessment, 14, 52, and 4 patients were graded as mild, moderate, and severe, respectively. On the other hand, 11, 51, and 8 patients had SSSA-Grade I, II, and III, respectively. Of all patients, 63 (90.0%) had consistent evaluation results, with Kappa2  = 0.762, whereas the remaining seven patients had an HFUS grade higher than the clinical. CONCLUSION: HFUS is a useful tool for dermatologists to monitor the treatment of moderate and severe acne vulgaris.

Pentagalloylglucose disrupts the PALB2-BRCA2 interaction and potentiates tumor sensitivity to PARP inhibitor and radiotherapy.

DNA damage repair plays a vital role in maintaining the genomic integrity of cells and has been exploited therapeutically in the treatment of cancer. We have previously demonstrated that the upregulation of CXorf67 in posterior fossa type A ependymoma sensitizes tumor cells to PARP inhibitors by suppressing the PALB2-BRCA2 protein-protein interaction (PPI). Here, we performed structure-based virtual screening of ∼2 million small molecular entities followed by NanoBiT-based screening, and determined that pentagalloylglucose (PGG) disrupts the PALB2-BRCA2 PPI. Structure-based molecular docking and in vitro binding affinity assays revealed that PGG occupies a well-defined binding groove in the tips of the fourth and fifth blades of the PALB2 WD40 domain. PGG reduces BRCA2 recruitment to DNA damage sites and inhibits the formation of RAD51 foci, suppressing homologous recombination repair. PGG also inhibits proliferation and survival in several cancer cell lines, including breast cancer and medulloblastoma cells, and suppresses the in vivo growth of tumor xenografts. Thus, PGG is a specific inhibitor of the PALB2-BRCA2 PPI, which has potential value in cancer treatment to sensitize tumors to PARP inhibitors and radiotherapy.

Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer.

As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.

Disability and Comorbidity of Mood Disorders and Anxiety Disorders With Diabetes and Hypertension: Evidences From the China Mental Health Survey and Chronic Disease Surveillance in China.

Background: The China Mental Health Survey was carried out using the same sampling frame with the China Chronic Diseases and Risk Factors Surveillance. This paper explores the relationship between the disability and the comorbidity of mood disorders and anxiety disorders with diabetes and hypertension. Methods: A large-scale nationally representative sample with both mental disorders and chronic diseases was collected from 157 Disease Surveillance Points in 31 provinces across China. Face-to-face interviews were conducted by trained lay interviewers to make diagnoses of mood disorders and anxiety disorders using the Composite International Diagnostic Interview. Diabetes and hypertension were diagnosed from self-report and blood examination or body measurement. Sampling design weights, non-response adjustment weights, and post-stratification adjustment weights were applied during the analyses of comorbidity and disability. Results: Totally 15,000 respondents had information of mental disorders and physical diseases. In the patients with mood disorders or anxiety disorders, the weighted prevalence rates of diabetes or hypertension were not higher than those in persons without the above mental disorders, but the weighed disability rates increased when having the comorbidity of hypertension (P < 0.05). The severity of disability was higher among patients with comorbidity of diabetes and anxiety disorders, or hypertension and mood disorders, compared with that among patients without the physical comorbidity (P < 0.05). After adjusted by age, gender and education, patients with comorbidity of mental disorders and physical disorders had the highest disability, followed by the patients with mental disorders only, and physical diseases only. Conclusions: The disability of mood disorders and anxiety disorders comorbid with diabetes and hypertension are more serious than that of any single disease. The relationship of mental and physical diseases is worth exploring in depth for comprehensive and integrated intervention to decrease the disability.

Clinical significance of chromosomal integrity in gastric cancers.

BACKGROUND: A whole-exome or targeted cancer genes panel by next-generation sequencing has been used widely in assisting individualized treatment decisions. Currently, multiple algorithms are developed to estimate DNA copy numbers based on sequencing data, which makes a comprehensive global glance at chromosomal integrity possible. We aim to classify gastric cancers based on chromosomal integrity to guide personalized therapy. METHODS: We investigated copy number variations (CNV) across the entire genome of 124 gastric carcinomas via exome or targeted sequencing. Chromosomal integrity was classified as chromosomal stability (CS), chromosomal instability (CIN) and intermediate state (CIN/CS) based on CNV results. Chromosomal integrity was correlated to molecular features and clinical characteristics. RESULTS: According the states of chromosomal integrity, gastric carcinomas can be stratified into two cohorts: CS and CIN. Our results showed a significant relationship between CIN status and TP53 mutation, but not RB1, phosphatase and tensin homolog (PTEN), or other reported DNA damage repair genes. The mutation frequency of the TP53 gene had great relevance. Our study initially revealed clinical significance of chromosomal integrity that CIN patients were prone to HER2-positive and mucinous adenocarcinoma, while CS patients were a diffuse subtype and poorly differentiated but had longer overall survival. CONCLUSIONS: We classified gastric carcinomas into two states of chromosomal integrity with clinical implications. The dichotomy is applicable to clinical transformation. We proposed that classifying gastric cancers based on chromosomal integrity would enable us to achieve personalized therapy for patients and may be beneficial to patient stratification in future clinical trials.