Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

ObjectiveTo investigate the mortality and years of life lost of pancreatic cancer in Baoshan District of Shanghai，from 2009 to 2021， and to provide scientific evidence for the prevention and control of pancreatic cancer in the future. MethodsThe death surveillance data of Baoshan District from 2009 to 2021 were collected from the Shanghai chronic disease surveillance information management system. Crude mortality， standardized mortality，potential years of life lost （PYLL）， potential years of life lost rate （PYLLR） ， average years of potential life lost （AYLL） ， annual percentage change （APC） were calculated to analyze the trend of mortality and life loss of pancreatic cancer. ResultsFrom 2009 to 2021， a total of 2117 deaths of pancreatic cancer were reported in Baoshan District， accounting for 7.05% of all cancer deaths. The average age of the death cases was （71.18±10.97）years. The youngest was 3 years old and the oldest was 96 years old. The death component ratio of pancreatic cancer increased with time （P<0.05）， and the average death age of women was higher than that of men （P<0.05）. The crude mortality of pancreatic cancer was 17.38/10⁵ in Baoshan District from 2009 to 2021， showing a rising tendency （P<0.05） with APC of 3.74%. The standardized mortality of pancreatic cancer was 7.84/10⁵. The crude mortality of pancreatic cancer was 19.71/10⁵ in men and 14.89/10⁵ in women， both showed a tendency towards a rise （P<0.05 ） with APC of 4.44% and 2. 89%， respectively. The crude mortality of pancreatic cancer showed a tendency towards a decline in residents at ages of 45 to 60 years （ P<0.05 ）， with APC of 4.74%. The PYLL and PYLLR of pancreatic cancer were 8 115 person-years and 0.67‰ in Baoshan District from 2009 to 2021， while the AYLL of pancreatic cancer was 3.83 years per person. The PYLL was higher in men than in women. ConclusionThe mortality rate of pancreatic cancer in Baoshan District shows an increasing trend. The healthy life of elderly and men is affected largely by pancreatic cancer. It is necessary to strengthen the health education on the prevention/control of pancreatic cancer and healthy life style， thereby improving the tertiary prevention system of pancreatic cancer.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Objective:To analyze the relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer.Methods:The clinicopathological data of 665 patients with gastric cancer were retrospectively analyzed. According to the presence of perineural invasion, the patients were divided into perineural invasion positive group and perineural invasion negative group. The relationship between perineural invasion and other clinicopathological factors and its effect on the prognosis of gastric cancer were analyzed. After eliminating the potential confusion bias between the two groups by propensity score matching (PSM) , the differences of 5-year cumulative survival rate between the two groups of gastric cancer patients were compared.Results:The incidence of perineural invasion was 17.0% (113 cases) . The binary logistic regression analysis showed that the depth of tumor invasion and vascular tumor thrombus were independent factors influencing the occurrence of gastric cancer perineural invasion (all P<0.001) . Univariate analysis showed that age (>60 years) , tumor diameter (>4 cm) , borrmann classification, depth of invasion, lymph node metastasis, TNM stage, degree of differentiation, vascular tumor thrombus, perineural invasion, tumor nodule, tumor site, resection site, and surgical operation were the influencing factors for the prognosis of patients with gastric cancer ( P<0.05) , but multivariate analysis showed that age (>60 years) , tumor diameter (>4cm) , depth of invasion, lymph node metastasis, and positive vascular tumor thrombi were independent risk factors affecting the prognosis of gastric cancer patients ( P<0.05) .However, perineural invasion cannot be an independent factor influencing the poor prognosis of gastric cancer in a multivariate analysis. Survival analysis was performed after propensity matching scores, and it was found that there was no statistically significant difference in the five-year survival rate between the perineural invasion positive group and the perineural invasion negative group (34.6% vs 43.0%; χ2=1.713; P=0.191) ,and there was no significant difference in the survival curve analysis between the two. Conclusion:Most patients with gastric cancer of perineural invasion have poor prognosis, but perineural invasion cannot be an independent prognostic factor for the prognosis of gastric cancer.

Objective:To detect the expression of fibroblast-specific protein 1 (FSP1/S100A4) , ɑ-smooth-muscle actin (ɑ-SMA) and fibroblast-activated protein (FAP-ɑ) in tumor-associated fibroblasts (TAFs) in papillary thyroid carcinoma (PTC) , and to investigate its relationship with the origination and development of PTC.Methods:The expression of FSP1/S100A4, ɑ-SMA and FAP-ɑ in normal thyroid and PTC was determined by SP method of immunohistochemistry, and the relationship between these indicators and important clinicopathological parameters were analyzed.Results:The positive expression of FSP1/S100A4, ɑ-SMA and FAP-ɑ was observed in PTC, but not detected in the follicular epithelium or stromal cells of normal thyroid. In addition, the expression of FAP-ɑ was significantly related to tumor size, lymph node metastasis and TNM classification ( χ2=6.833, P<0.05; χ2=10.296, P<0.05; χ2=4.910, P<0.05) . The expression of ɑ-SMA was positively related to the invasion of capsule and lymph node metastasis ( χ2=6.008, P<0.05; χ2=11.766, P<0.05) . The expression of FSP1/S100A4 was negatively related to the clinicopathological parameters above ( P>0.05) in PTC. Conclusion:TAFs in PTC may indicate the infiltration and metastasis, which provideds new thinking for the treatment strategies of papillary thyroid carcinoma.

Objective To explore the clinical effect of inner heating dry needle therapy on nonspecific chronic neck pain (NCNP). Methods From October, 2017 to March, 2018, 60 patients with NCNP were randomly divided into needle group (n=30) and magner group (n=30). The needle group received inner heating dry needle therapy, and the magner group received hot magner therapy. They were measured the strain ratio (SR) of bilateral trapezius muscles, scalp clamp muscles, cephalospinal muscles, semispinalis muscles and multifidus muscles with ultrasound elastography before, and one week and one month after treatment, respectively, while they were assessed with Visual Analogue Scale (VAS) of pain and Neck Disability Index (NDI). Results The scores of VAS and NDI decreased in both groups one week and one month after treatment (t>2.693, P<0.05), and decreased more in the needle group than in the magner group (F>8.048, P<0.001). SR of all the muscles decreased in the needle group one week and one month after treatment (F>6.22, P<0.01), and only decreased in the right cephalospinal muscles in the magner group (F=4.35, P<0.05).Conclusion Inner heating dry needle therapy could recover the neck muscle elasticity to relieve pain and improve ceivical function in patients with NCNP.

Objective To evaluate the long-term efficacy of antiretroviral therapy and drug resistance among human immunodeficiency virus-1(HIV-1)-infected children in Yunnan.Methods In this retrospective study,CD4+T cell counts,HIV viral loads and genetic drug resistance results were obtained from HIV-1-infected children who were treated with antiretroviral treatment between January 2004 to July 2015.Results A total of 1 078 HIV/acquired immune deficiency syndrome(AIDS)children were treated with antiviral therapy.Before treatment,the average CD4+cell number was(466.8 ± 397.2)cells/μL. The percentages of children with CD4+cell count >750 cells/μL after 1-year,3-year,5-year and 8-year treatment were 54.31%,62.87%,68.46% and 74.19%,respectively.Virological failure occurred in 150 HIV/AIDS children(13.9%),and the virological failure rate was 4.3/100 child-years.Among those 150 patients with virological failure,104 cases(69.33%)exhibited genetic resistance to antiretroviral drugs.The prevalent mutations associated with drug resistance were M 184V/I(75.0% [78/104]), K103N(43.3%[45/104]),G190A(29.8%[31/104]),Y181C(22.1%[23/104]),T215Y/F(20.2%[21/104]).Conclusions After long-term antiretroviral treatment,most of the HIV-infected children have restored the immunity and suppressed HIV viral replication successfully.HIV resistance is the main cause of virological failure.Drug resistance mutations mainly occur in nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor,and the resistance rate of proteinase inhibitor is low.Early genetic resistance testing and switch to second-line therapy will improve the treatment outcome.

Objective To observe the effects of percutaneous endoscopic gastrostomy (PEG)on mortality and complications in patients with persistent dysphagia after stroke using a points scoring system for selecting PEG indication.Methods A total of 75 patients were divided into low score group without PEG,high score group without PEG and low score group with PEG (n=25 each).The follow-up period was 18 months,and the differences in complications,mortalities and survival periods among groups were compared.Results The number of times of aspiration pneumonia was (1.36± 1.44) in low score group,(1.96±2.28) in high score group,(0.36±0.64) in low score group with PEG,with statistically significant differences among three groups (H=7.148,P=0.028).No difference in the morbidity of aspiration pneumonia was found between low score group and high score group (P=0.189).The number of times of aspiration pneumonia was decreased in low score groups after PEG versus in low score group without PEG (P=0.030) and in high score group (P＜0.01).The numberof times of gastrointestinal hemorrhage was (0.48± 0.77)in low score group,(0.64± 0.91) in high score group,(0.12±0.33) in low score group with PEG,with statistically significant differences among three groups (H=5.532,P =0.063).No statistically significant difference in gastrointestinal hemorrhage was found between low score groups and low score group after PEG (P=0.430),as well as between low score group and low score group with PEG (P=0.079).The morbidity of gastrointestinal hemorrhage was lower in low score group than in high score group (P=0.012).The survival rate at the observation end was 88.0％ (22/25),52.0％ (13/25) and 92.0％ (23/25) in low score group,high score group and low score group with PEG,respectively,with statistically significant difference among the three groups (x2 =7.906,P =0.001).Kaplan-Meier survival curve showed that the survival period were longer in the low score group with or without PEG than in high score group (P＜0.01),but no statistically significant difference was found between low score groups with or without PEG (P=0.626).Conclusions The reasonable evaluation using a points-scoring system before PEG might predict the prognosis of such patients:the higher score would indicate higher mortality.PEG operation for low score group with better condition could decrease the aspiration pneumonia and decrease gastrointestinal hemorrhage significantly,but could not prolong general survival time and decrease general mortality.

PURPOSE: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. RESULTS: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. CONCLUSION: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.
Carcinogenesis ; Cell Cycle Checkpoints ; Cell Line ; Cell Proliferation* ; Chromatin ; Cyclin D1 ; Down-Regulation ; Polymerase Chain Reaction ; Protein Kinases ; Receptors, Thyrotropin* ; Reverse Transcription ; RNA, Long Noncoding* ; RNA, Untranslated ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyrotropin*