The trend of AIDS in China: A prediction and comparative analysis with G20 countries based on the Global Burden of Disease Study 2019.

Background: In China, AIDS has become the most severe notifiable infectious disease. The study aimed to analyse and predict the trend of AIDS in China and compared with Group of Twenty (G20) countries. Methods: We utilised incidence, mortality or disability-adjusted life years (DALY), age-standardised rates (ASR), average annual percentage changes (AAPC) to estimate the trend via GBD 2019. The Joinpoint regression analysis was applied to identify the most significant years of change. We explored the relationship between AAPC and social development index (SDI) or health care access and quality (HAQ), and predicted trends for the next 20 years. Results: The DALY in G20 increase of 340.42%, and 794.50% in China. The age-standardised DALY rate (ASDR) in G20 was 309.49 (95% uncertainty interval (UI) = 284.69, 350.58) in 2019, with an AAPC of 4.30. Among G20, the United States had the highest DALY in 1990, but it experienced a significant decline. In China, the ASDR was 98.15 (95% UI = 78.78, 119.58) with the 5th AAPC ranking. In term of gender, the incidence, mortality, DALY, and ASR of them in China and G20 were all higher in males. Furthermore, the gender gap in China had been widening. The most significant periods of ASDR increase in China were 1990-1995 and 2013-2016, and 1990-1994 in G20. The prediction for DALY indicated that high SDI countries were expected to exhibit a stable or declining trend, while low SDI countries showed an upward trend. China demonstrated a 57.66% increase in 2040 compared to 2019. Conclusions: AIDS continues to be a significant burden. In China, the ASIR exhibited a decline trend in certain age groups, while the ASMR and ASDR continued to increase, with a widening gender disparity. In addition, according to our predict results, some countries could not achieve the 2030 Agenda for Sustainable Development set by the UNAIDS. Therefore, it is necessary to establish more effective and targeted measures, as well as actively explore new treatment approaches.

Primary synovial sarcoma of the thyroid gland: a CARE compliant case report and literature review.

Rationale: Synovial sarcoma is a subtype of soft tissue sarcoma. Synovial sarcoma in the head and neck region is relatively unusual. Primary synovial sarcoma of the thyroid gland (PSST) is first reported in 2003 by Inako Kikuchi. PSST is extremely rare with only 15 cases documented globally. PSST shows rapid disease progression and a relatively poor prognosis. However, diagnosis and therapy are challenging for clinical surgeons. In this article, we reported the 16th PSST case and reviewed the PSST cases globally for further clinical application. Patient concerns: The patient was referred to us because of gradually worsened dyspnea and dysphagia for 20 days. Physical examination showed a 5 × 4 cm mass with a clear boundary and good mobility. Contrast-enhanced ultrasonography (CEUS) and computed tomography (CT) showed a mass in the isthmus of the thyroid gland. The imageology diagnosis tends to be a benign thyroid nodule. Diagnosis: After surgery, histopathology, immunohistochemistry, and fluorescence, in situ hybridization indicated the mass to be primary synovial sarcoma of the thyroid gland with no local and distant metastasis. Interventions: The patient underwent total thyroidectomy and dissected the lymph nodes in the central compartment. This patient received postoperative chemotherapy (a combination of ifosfamide and epirubicin for five cycles). Patients tolerated chemotherapy well. No recurrence was found during the 9-month follow-up. Lessons: Although PSST is an extremely rare disease, we should raise our awareness when we encounter a rapidly growing, cystic-solid mixed thyroid mass with neck compression symptoms to avoid misdiagnosis. Intraoperatively, surgeons should refine surgical procedures to avoid capsular rupture and tumor local implantation metastasis. Intraoperative frozen section pathology is necessary sometimes, especially when the diagnosis could not be established before surgery.

The burden of liver cirrhosis in mortality: Results from the global burden of disease study.

Background: Liver cirrhosis-related death is a serious threat worldwide. The number of studies exploring the mortality trend of cirrhosis caused by specific etiologies was limited. This study aimed to demonstrate the pattern and trend based on the data of global burden of disease (GBD). Methods: The data of cirrhosis mortality were collected from the GBD 2017. The Age standardized mortality rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the temporal trend of liver cirrhosis mortality by etiologies, regions, sociodemographic index (SDI), and sexes. Results: Globally, mortality cases of cirrhosis increased by 47.15%. Although the global ASR of cirrhosis mortality remained stable during this period, the temporal trend varied in etiologies. The ASR of mortality caused by hepatitis C virus (HCV), alcohol consumption, and non-alcoholic steatohepatitis (NASH) increased with an EAPC of 0.17 (95% CI, 0.14-0.20), 0.20 (95% CI, 0.16-0.24), 1.00 (95% CI, 0.97-1.04), respectively. A decreasing trend of ASR was found among the causes of hepatitis B virus (BV) and other causes. The increased pattern was heterogeneous worldwide. The most pronounced increase trend was found in middle-high SDI regions and Eastern Europe. Contrarily, the most pronounced decrease trend was found in low SDI regions and Western Sub-Saharan Africa. Conclusion: Cirrhosis is still a public health problem. The growth trend of cirrhosis mortality caused by HCV was slowed by promoting direct-acting antiviral therapy. Unfortunately, we observed an unfavorable trend in etiologies for alcohol consumption and NASH, which indicated that more targeted and specific strategies should be established to limit alcohol consumption and promote healthy lifestyles in high-risk countries, especially in middle-high SDI regions and Eastern Europe.

A Risk Model Developed Based on Necroptosis Predicts Overall Survival for Hepatocellular Carcinoma and Identification of Possible Therapeutic Drugs.

Background: Necroptosis is a form of regulatory cell death (RCD) that attracts and activates immune cells, resulting in pro-tumor or anti-tumor effects. The purpose of this study was to investigate genes associated with necroptosis, to construct a risk score for predicting overall survival in patients with hepatocellular carcinoma, and to find potentially effective drugs. Methods: The three algorithms ssGSEA, EPIC, and ESTIMATE were used to quantify the immune cell infiltration of the samples, differentially expressed genes (DEGs) analysis, and weighted gene co-expression network analysis were used to screen necroptosis related genes. Variables were screened according to random survival forest analysis, and combinations with significant p-values and a low number of genes were defined as prognostic signatures by using log-rank test after gene combination. Based on the sensitivity data of PRISM and CTRP2.0 datasets, we predicted the potential therapeutic agents for high-NRS patients. Results: Seven genes such as TOP2A were used to define necroptosis-related risk score (NRS). The prognostic value of risk score was further validated, where high NRS was identified as a poor prognostic factor and tended to have higher grades of histologic grade, pathologic stage, T stage, BCLC, CLIP, and higher AFP. Higher NRS was also negatively correlated with the abundance of DCs, Neutrophils, Th17 cells, Macrophages, Endothelial, and positively correlated with Th2 cells. Necroptosis is often accompanied by the release of multiple cytokines, and we found that some cytokines were significantly correlated with both NRS and immune cells, suggesting that necroptosis may affect the infiltration of immune cells through cytokines. In addition, we found that TP53 mutations were more common in samples with high NRS, and these mutations may be associated with changes in NRS. Patients with high NRS may be more sensitive to gemcitabine, and gemcitabine may be an effective drug to improve the prognosis of patients with high NRS, which may play a role by inhibiting the expression of TOP2A. Conclusions: We constructed a necroptosis-related scoring model to predict OS in HCC patients, and NRS was associated with immune response, TP53 mutation, and poor clinical classification in HCC patients. In addition, gemcitabine may be an effective drug for high-NRS patients.

DALY trend and predictive analysis of COPD in China and its provinces: Findings from the global burden of disease study.

Background: Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease in the world, especially in China. Few studies have explored the trend of COPD in China and its provinces. This study aimed to demonstrate and predict the trend of COPD DALY in China and its provinces based on the global burden of disease (GBD) data. Methods: The data on COPD disability-adjusted life year (DALY) were collected from GBD 2017, GBD 2019, and the National Bureau of Statistics of China. The age-standardized rate (ASR) was used to evaluate the trend of COPD DALY by gender, age, and risk factors in China and its provinces. In addition, the trend of COPD considering the aging population in the next 10 years was also predicted. Results: In China, the COPD DALY was 20.4 million in 2017, which decreased to 24.16% from 1990 to 2017. Most provinces showed a downward trend, with the exception of Taiwan which increased by 127.78%. The ASR of DALY was 1445.53 per 100,000 people in 2017 and demonstrated a significant decrease. Among all provinces, only Taiwan (97.78%) and Hubei (2.21%) demonstrated an increased trend of ASR. In addition, Tibet ranked third with a decline of 56.95%, although its ASR was the highest in 1990. Smoking and air pollution were the main risk factors for COPD and varied with regions, gender, and age. The proportion of COPD DALY attributable to smoking was higher in the middle-aged and elderly male population and did not decrease in China. Moreover, the ASR attributable to air pollution of the elderly decreased significantly in China. Socio-demographic index (SDI) and educational level were also found to be related to ASR. By predicting the ASR trend in the next 10 years, we found that the ASR attributable to smoking might increase significantly among men. The ASR attributable to air pollution showed a significant decrease in women. Unfortunately, ASR attributable to second-hand smoke was found to increase in women. Conclusion: Chronic obstructive pulmonary disease is the leading contributor to the burden of global diseases. Although China and its provinces demonstrated a downward trend of COPD DALY, some provinces still faced challenges. Moreover, ASR attributable to risk factors was different in regions, gender, age, and years. The predicted trend of COPD was also different. Therefore, more targeted strategies should be formulated to reduce the burden of COPD in China and its provinces.

Case Report: A papillary thyroid microcarcinoma patient with skip lymph node metastasis and multiple distant metastasis.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Papillary thyroid microcarcinoma (PTMC) is defined as PTC with a diameter less than 1 centimeter. Most lymph nodes of PTC patients have metastasized to the central neck, and a few lymph nodes have metastasized to the lateral neck. Skip lymph node metastasis, that is, lateral cervical lymph node metastasis without central lymph node metastasis, is even less common. Additionally, distant metastasis of PTMC is also rare, mainly occurring in the lung and bone. Here, we reported a case of PTMC patient with skip lymph node metastasis and multiple distant metastasis. The patient presented with a huge shoulder mass and the primary tumor was found to originate from the thyroid. However, the patient only suffered with PTMC via postoperative pathological results, and interestingly, the patient only had skip lymph node metastasis. Thus, we should focus on PTMC patients with lateral cervical lymph nodes metastasis, especially those with skip metastasis. In addition, this case provides a new perspective for us to understand of skip lymph metastasis and distant metastasis of PTMC.

The global burden of thyroid cancer and its attributable risk factor in 195 countries and territories: A systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Thyroid cancer is a growing threat to human health. Few studies have explored trends of thyroid cancer and relationships with social development factors. In this study, we explored the trend and relationship based on GBD. METHODS: By using GBD study, we obtained detailed data of thyroid cancer. Incidence, mortality and DALY were used to assess epidemiological characteristics. ASR and EAPC were used to estimate the trend. RESULTS: Globally, the incidence significantly increased from 1990 to 2017, especially in high-income regions. Males and middle SDI region demonstrated a higher increase of age-standardized incidence rates. Unlike incidence trend, mortality trend showed a minor increase, and even showed a decreasing trend in some regions such as Eastern Sub-Saharan Africa. Additionally, the DALY trend also demonstrated a slightly increase with an EAPC of 0.77 (95% CI 0.73-0.81). More significant increase of DALY was found in males, middle SDI region and high-income Asia Pacific. The incidence of thyroid cancer peaked in middle-aged people, while the mortality and DALY peaked in elder-aged. Moreover, the proportion of thyroid cancer deaths contributable to high BMI was highest in developed countries and middle-aged people. CONCLUSIONS: Thyroid cancer is a public health problem worldwide. Over-diagnosis might be partly responsible for its rising trend. It remains us to revise the guidelines to avoid unnecessary burdens. Moreover, we should pay attention to the risk factors of thyroid cancer. More targeted measures should be formulated to improve potential environmental and lifestyle-related factors which might contribute to rising trend of thyroid cancer.

TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell.

Background: Oxaliplatin is the first-choice chemotherapy method for patients with advanced colon cancer. However, its resistance leads to treatment failure for many patients. In our experiments, we aim to elucidate the associations among TRIM29 protein, mutant P53, and the resistance of colon cancer cells to oxaliplatin. Methods: HCT116 and HT-29 cells were cultured and transfected with plasmids pIRES2-ZsGreen1-TRIM29-flag. Western blot and real-time qRT-PCR were utilized to examine the protein and mRNA expressions of TRIM29 and other related markers, respectively. MTT assay was utilized to determine the cell growth rate and generate the inhibition curve. Continuous culture in low-concentration oxaliplatin was conducted to construct oxaliplatin-resistant cell lines. The coimmunoprecipitation method and immunofluorescence detection were used to examine the interaction between TRIM29 and mutant P53 protein in HT29 cells. Results: We successfully transfected pIRES2-ZsGreen1-TRIM29-flag into HCT116 and HT29 cells, which were utilized in the whole experiments. TRIM29 significantly increased the sensitivity of P53 mutant colon cancer cell HT29 to oxaliplatin. The oxaliplatin-resistant model of P53 mutant colon cancer cell HT29 was successfully constructed. TRIM29 physically bound with mutant P53 and retained it in the cytoplasm from the nucleus, which inhibited its transcription function of downstream genes such as MDR1. In addition, TRIM29 successfully reversed the resistance of HT29-OX resistant cell model to oxaliplatin. Conclusion: In mutant P53 colon cancer cell HT29, TRIM29 greatly increased the sensitivity of HT29 to oxaliplatin and reverse oxaliplatin resistance. The underlying mechanism is TRIM29 may increase the sensitivity of HT29 to oxaliplatin by blocking the transcriptional function of mutant P53, which inhibits the transcription function of its downstream gene such as MDR1.

The incidence trends of liver cirrhosis caused by nonalcoholic steatohepatitis via the GBD study 2017.

Nonalcoholic steatohepatitis (NASH) has rapidly become the most common cause of chronic liver diseases. We aimed to explore the incidence and distribution characteristics of NASH by sex, region and sociodemographic index (SDI). We collected data, including sex and region, on NASH-related liver cirrhosis from the 2017 GBD study. The age-standardized incidence rates (ASRs) and estimated annual percentage changes (EAPCs) were used to estimate the incidence trend and distribution characteristics. Globally, the incidence of liver cirrhosis caused by NASH increased from 178,430 cases in 1990 to 367,780 cases in 2017, an increase of approximately 105.56%. The ASR of NASH increased by an average of 1.35% per year (95% CI 1.28-1.42). Meanwhile, large differences in the ASR and the EAPC were observed across regions. The middle-high SDI region had the highest increase among all five SDI regions, followed by middle SDI region. In addition, Eastern Europe, Andean Latin America and Central Asia showed a more significant growth trend of ASR. In contrast, the high SDI region demonstrated the slowest increasing trend of ASR, and the high-income Asia Pacific demonstrated a decreasing trend among the 21 regions. Liver cirrhosis has caused a huge and rising health burden in many countries and regions. In addition, with the growth of obesity, population and aging, NASH might replace viral hepatitis as the most important cause of liver cirrhosis in the near future. Therefore, appropriate interventions are needed in coming decades to realize early diagnosis and prevention of NASH-related liver cirrhosis.

Intra-platelet serotonin and YAP contributed to poor prognosis of hepatocellular carcinoma.

AIMS: Intra-platelet 5-HT (IP 5-HT) and YAP exhibit an important role in hepatocellular carcinoma (HCC). The aim of the study was to investigate whether IP 5-HT and YAP could affect the progression and prognosis of HCC. METHODS: 5-HT level and YAP expression were measured and were compared between HCC patients and control patients. By grouping HCC patients, we analyzed clinical indicators and survival. The predictive nomogram was established by R software according to the risk factors obtained from multivariate analysis. RESULTS: Higher IP 5-HT level and higher YAP expression were associated with poorer prognosis. In addition, they were also associated with BCLC stages. Higher IP 5-HT was found to be related with higher international normalized ratio (INR) (p = 0.040), more death (p = 0.015) and higher YAP expression (p < 0.001). Similarly, higher YAP expression was proved to be associated with lower platelet counts (PLT) (p = 0.032), smaller tumor size (p = 0.017), more death (p < 0.001) and higher IP 5-HT (p < 0.001). In addition, alkaline phosphatase (ALP), YAP and tumor size were proved to be independent risk factors. By using risk factors, we have established a prognostic prediction nomogram for HCC patients. In the prognostic prediction nomogram, patients with higher scores would have poorer prognosis. CONCLUSIONS: IP 5-HT and YAP might affect the progression and prognosis of HCC through synergistic effect. Moreover, IP 5-HT might affect HCC by regulating YAP expression. Thus, both of them might be potential therapeutic targets. By establishing the prognostic prediction nomogram, we could improve the prediction system.

The burden of liver cirrhosis and underlying etiologies: results from the global burden of disease study 2017.

BACKGROUND: To evaluate the pattern and prevalence trends of liver cirrhosis caused by specific etiologies. RESULTS: Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The ASR increased 0.75 per year. The most pronounced increases were found in middle-high and high socio-demographic index (SDI) regions, especially in the Caribbean and Latin America. Among the etiologies, non-alcoholic steatohepatitis (NASH) related liver cirrhosis accounted for 59.46% of the cases. The ASR increased 1.74 per year, and the increase was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol also increased in both sexes and all SDI regions. In contrast, the ASR of liver cirrhosis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) decreased, especially in middle and low-middle SDI regions. CONCLUSIONS: Though the number of people suffering from HBV and HCV decreases, liver cirrhosis is still a major threat to health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continues to grow. Thus, more targeted and specific strategies should be established based on etiology and prevalence trends of liver cirrhosis. METHODS: We collected data based on Global Burden of Disease (GBD) 2017 study. The age standardized prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trends in prevalence by population, etiologies and regions.

LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc.

The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.

Axis of serotonin -pERK-YAP in liver regeneration.

BACKGROUND AND AIM: Serotonin and YAP exhibit a vital role in regulating cell proliferation and wound-healing response. The aim of the study was to investigate whether 5-HT could promote liver regeneration by activating YAP. METHODS: PH models were established by WT and TPH1-/- mice. ELISA, RT-PCR, western blot, immunohistochemistry, flow cytometry and MTT assay were used to assess the level of 5-HT and YAP and proliferation after PH. RESULTS: We found that 5-HT level was lower in the serum and liver of TPH1-/- mice. After PH, TPH1-/- mice, lacking in 5-HT, demonstrated worse regenerative ability and suffered more severe liver injury. Additionally, YAP expression was also lower in TPH1-/- mice. Moreover, we found that YAP expression was prominent within the first three days following PH. Similarly, 5-HT could promote cell proliferation by upregulating YAP expression in L-O2 cells. As predicted, using YAP-siRNA sharply reduced the proliferative capacity mediated by 5-HT. Further study also indicated that ERK participated in the regulation of YAP induced by 5-HT. By using an ERK inhibitor, the YAP expression and cell proliferation induced by 5-HT were both suppressed. Although YAP-siRNA was used to block YAP expression, pERK and ERK expression were not affected. Taken together, these data showed that 5-HT contributed to liver regeneration by regulating YAP expression, which at least in part, was by activation of pERK. CONCLUSION: A role of the 5-HT-pERK-YAP axis in liver regeneration emerged from our study and might be a potential target to promote regeneration and injury repair.

Serotonin and YAP/VGLL4 Balance Correlated with Progression and Poor Prognosis of Hepatocellular Carcinoma.

YAP-TEAD complex plays an important role in tumorigenesis. 5-HT is proved to upregulate YAP expression by our previous study and VGLL4 is found to compete with YAP for binding to TEAD in several of cancers. Here, we investigated whether 5-HT could affect progression and prognosis of hepatocellular carcinoma (HCC) patients and regulate YAP/VGLL4 balance. We found that 5-HT and YAP/VGLL4 ratio were higher in HCC patients and closely related with progression and poor prognosis. Furthermore, 5-HT level, YAP/VGLL4 ratio and tumor size were proved as independent risk factors of HCC patients in our study. Based on the independent risk factors, nomogram was established to exactly predict prognosis of HCC patients. Additionally, the study revealed that a higher total point of the nomogram was closely correlated with poorer prognosis. As a result, 5-HT might contribute to the progression and poor prognosis of hepatocellular carcinoma via regulating YAP/VGLL4 balance. Therefore, the established nomogram based on the independent risk factors may become an important part of HCC prediction system and YAP/VGLL4 balance may be a potential therapeutic target in future.

Pharmacological inhibition of TRPV4 channel suppresses malignant biological behavior of hepatocellular carcinoma via modulation of ERK signaling pathway.

TRPV4 (transient receptor potential vanilloid 4), a member of the TRP superfamily, has been reported to correlate with several different forms of cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC) remains unclear. The present study demonstrated that elevated expression of TRPV4 was shown in HCC tumor tissues when compared with paired non-tumoral livers both in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was highly associated with histological grade (P = 0.036) and the number of tumors (P = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis and decreased the migration capability by attenuating the epithelial-mesenchymal transition (EMT) process in vitro. The p-ERK expression was apparently repressed after treatment with the TRPV4 antagonist, further blockade of the ERK pathway with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse xenograft models, intraperitoneal injection of HC-067047 could obviously suppress tumor growth and induce apoptosis in vivo. Together, our studies showed that the antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be attributed to the suppression of EMT process and inactivation of p-ERK which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 channel may be an option for HCC treatment.