Prevalence of depression, anxiety in China during the COVID-19 pandemic: an updated systematic review and meta-analysis.

Background: Mental health risks associated with the aftermath of the COVID-19 pandemic are often overlooked by the public. The aim of this study was to investigate the effects of the COVID-19 pandemic on depression and anxiety disorders in China. Methods: Studies were analyzed and extracted in accordance with the PRISMA 2020 flowchart. The studies were screened and extracted using electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov according to the predefined eligibility criteria. The Cochrane Review Manager software 5.3.1 was used for data analysis and the risk of bias assessment. Results: As of 2023, a total of 9,212,751 Chinese have been diagnosed with COVID-19 infection. A total of 913,036 participants in 44 studies were selected following the eligibility criteria, the statistical information of which was collected for meta-analysis. The pooled prevalence of depression and anxiety were 0.31 (95% CI: 0.28, 0.35; I2 = 100.0%, p < 0.001) and 0.29 (95% CI: 0.23, 0.36; I2 = 100.0%, p < 0.001), respectively. After performing a subgroup analysis, the prevalence of depression among women, healthcare workers, students, and adolescents was 0.31 (95% CI: 0.22, 0.41), 0.33 (95% CI: 0.26, 0.44), 0.32 (95% CI: 0.26, 0.39), and 0.37 (95% CI: 0.31, 0.44), respectively. Conclusion: The prevalence of depression and anxiety among the Chinese was overall high. Monitoring and surveillance of the mental health status of the population during crises such as sudden global pandemics are imperative. Systematic review registration: https://clinicaltrials.gov/, identifier [CRD42023402190].

[Progress of researches on mechanisms of acupuncture therapy for insulin resistance].

Insulin resistance (IR) is a common pathophysiological basis of many chronic diseases, such as obesity, type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease, cerebral vascular disease, cardiovascular and neurodegenerative diseases, etc. Acupuncture therapy has been demonstrated to have a positive role in reducing IR level in clinical practice. In the present paper, we summarized development of researches on the mechanism of acupuncture therapy underlying improvement of IR in recent 10 years from 1) regulating expression of hypothalamic phosphatidylinositol-3-kinase (PI3K)-p85 and PI3K-P110 proteins in obesity rats; 2) regulating the levels of some related proteins of insulin target tissues (liver and skeletal muscle), such as insulin receptor substrate-1 (IRS)-1 and -2, glucose transporter mRNAs and proteins, sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthetase proteins; 3) suppressing inflammatory reaction of liver tissue and down-regulating serum adiponectin in T2DM rats; 4) raising the activity of superoxide dismutase (SOD) and reducing the levels of reactive oxygen species, and malondialdehyde (MDA) contents of quadriceps femoris in spontaneous IR rats; and 5) attenuating structural injury of pancreas islet and apoptosis of pancreatic ß cells in diabetes rats. Multi-levels and various systems of the neuro-endocrine-immune networks are involved in the actions of acupuncture in the improvement of IR. In the future, more attention should be paid to the study on the acupoint specificity, suitable acupoint combinations and stimulus parameters in clinical treatment of IR related various metabolic diseases, further optimizing clinical treatment protocols.

[Eletroacupuncture improves lipid metabolic disorder by regulating hepatic AMPK/p38 MAPK/RRARγ signaling in rats with high-fat diet-induced insulin resistance].

OBJECTIVE: To observe the effect of eletroacupuncture (EA) intervention on lipid metabolism and expression of AMP-activated kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK) and peroxisome proliferator-activated receptor γ (PPARγ) protein in the liver in rats with insulin resistance (IR), so as to reveal its mechanisms underlying improvement of IR. METHODS: Forty male SD rats were randomly divided into blank control, model, medication, and EA groups (n＝8 in each). The IR model was established by feeding the rats with high-fat diet for 12 weeks. After successful establishment of model, the rats in the blank control group and model group were fixed in the self-made rat bag without receiving any treatment. The rats in the medication group were treated by gavage of pioglitazone (10 mL/kg). EA (2 Hz /100 Hz, 1 mA) was applied to bilateral "Fenglong"(ST40) and "Sanyinjiao"(SP6) for 20 min, once a day, for continuous 14 days for rats in the EA group. The ultrastructure of the liver tissue was observed by transmission electron microscope (TEM). Blood samples were taken from the abdominal aorta for detecting serum C-peptide (C-P), adiponectin (ADP), leptin (LEP) and resistin (RES) contents using enzyme linked immunosorbent assay (ELISA). The expression levels of AMPK, p38 MAPK and PPARγ proteins in the liver tissue were detected by Western blot. RESULTS: After modeling, the contents of serum C-P, LEP and RES, and the expression of liver p38 MAPK protein were significantly up-regulated (P<0.01, P<0.05), and the content of ADP and expression of AMPK and PPARγ significantly down-regulated in the model group compared with the blank control group (P<0.01). The increased contents of C-P, LEP and RES, and p38 MAPK protein expression and the decreased serum ADP and hepatic AMPK and PPARγ expression levels were completely reversed in both the EA and medication groups relevant to the model group (P<0.01, P<0.05). No significant differences were found between the EA and medication groups in up-regulating the levels of ADP, AMPK and PPARγ and in down-regulating the levels of C-P, LEP, RES and p38 MAPK(P>0.05). Outcomes of TEM showed that morphological structure of liver mitochondria was damaged, including a large number of lipid droplets, being blur in appearance, rupture of partial membrane, dissapearance of partial mitochondrial crests with vacuolus-like appearance and decrease of rough endoplasmic reticulum in the model group, which was relatively milder in both EA and medication groups. CONCLUSION: EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in lowering the activity of fatty acid synthesis-related enzymes and regulating AMPK/p38 MAPK/PPARγ signaling to improve IR in the liver tissue.

Effect of Over-nutrition in Postnatal Life on Growth of Female SD Rats / 中山大学学报(医学科学版)

@#【Objective】 To guide the nutritional intervention of children in the clinical practice ，by exploring the effect of over-nutrition in postnatal life on growth of the female SD rats.【Methods】We established the rat model of intra? uterine growth retardation（IUGR）through diet restriction in pregnant rats and selected female newborn rats that met the criteria as the experimental group（group I）. Group I was randomly divided into control group（group IC）and small group（group IS）. Fifty-eight female newborn rats with normal diet in pregnant period（group C）were also divided into control group（group CC）and small group（group CS）. After 21-days-lactation，group IC and group CC were randomly subdivided into 4 rats per cage，and then fed with normal diet，while group IS and group CS were fed with high fat diet. We measured the body weight and the body length of each rat every week. Serum fasting insulin，fasting blood glucose，IGF-1，IGF- BP3 levels，and rat insulin sensitivity index（ISI）were measured at different growth and development stages.【Results】 The body weight and body length of group IS were higher than those of group IC（P<0.05）；the same was true for group CS and group CC. In the different growth and development stages，the FINS，FBG，IGF- 1 and IGF- BP3 of group IS were higher than those of group IC（P < 0.05），the ISI was lower than that of group IC（P < 0.05）. Besides，the FINS，FBG of group CS were higher than those of group CC and the ISI of group CS was lower than that of group CC in the 75 days after birth（P < 0.05）.【Conclusions】We found that those small for gestational age infants can be added nutrition appropriately for rapid catch-up，but it is necessary to evaluate the growth index closely and adjust the nutrition on time. Children with normal intrauterine development also need to prevent over-nutrition.

Effects of Early Life Nutritional Status on Weight Catch-up Growth，Puberty Initiation and Obesity in Female Rats with Intrauterine Growth Retardation / 中山大学学报(医学科学版)

@#【Objective】To investigate the effects of different nutritional status in early life on weight catch-up，puberty initiation and obesity in rats with intrauterine growth retardation（IUGR）.【Methods】IUGR model of newborn rats was established by limiting diet during pregnancy in SPF rats. Female newborn rats were used in the experiment. IUGR rats were divided into two groups：small litter IUGR group（SL-IUGR）and common feeding IUGR group（CF-IUGR）. Rats of normal birth weight served as normal control group（NC）. The SL-IUGR group was used to simulate overfeeding in lactation period. After weaning，the rats in the three groups were fed with basic diet. The weights were measured at postnatal 1，7，14，21，35，42 and 75 days. The time of vaginal orifice opening（VO）was recorded. The levels of estradiol（E2），luteinizing hormone（LH）and follicle estrogen（FSH）were examined on the 21 d and the 35 d.【Results】The birth weight of IUGR rats was（4.92±0.18）g，which was significantly lower than that in the control group（6.00±0.29 g，P < 0.001）. IUGR rats showed weight growth catch- up on the 14th day. The body weight of SL- IUGR group was higher than that of control group from 14 to 75 d. The body weight of CF-IUGR group lagged behind that of control group from 1 to 75 d，the difference was statistically significant（P < 0.05）. The vaginal opening time of female IUGR rats in SL- IUGR group was （29.88 ± 1.81）d，which was significantly earlier than that of CF- IUGR group（32.03 ± 2.11）days（P = 0.044）. There was a correlation between body weight of the 21 d and vaginal opening time in IUGR rats，Rs = -0.174，P = 0.039. The besity rates of puberty and adulthood of IUGR rats in SL-IUGR group were 28.33% and 21.67%，which were significantly higher than those in CF-IUGR group（7.5%，6.25%；P = 0.001，0.007）. The weight growth rate of adolescent obese IUGR rats at 7 and 21 d was higher than that of non-adolescent obese rats，and the weight growth rate of adult obese IUGR rats at 7 and 35 d was higher than that of non-adolescent obese rats. The difference was statistically significant（P < 0.05）. Binary Logistic regression analysis of vaginal opening time and adult obesity in IUGR rats′ group OR = 0.419，P = 0.24. The time of vaginal orifice opening was not an independent factor of adult obesity. 【Conclusions】The improvement of nutrition level in the early stage of life is beneficial to weight catch-up of IUGR，and the overweight catch-up during lactation can lead to puberty and adulthood obesity of IUGR rats，as well as the advance of vaginal opening time.

CBX1 Indicates Poor Outcomes and Exerts Oncogenic Activity in Hepatocellular Carcinoma.

Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion. Patients with elevated expression of CBX1 were frequently accompanied with unfavorable overall and disease-free survivals in two independent cohorts consisting of 648 HCC cases. The prognostic value of CBX1 was further confirmed by stratified survival analyses. Multivariate cox regression model suggested CBX1 as an independent factor for overall survival (hazard ratio = 1.735, 95% confident interval: 1.342-2.244, P < .001). In vitro data demonstrated that CBX1 overexpression promoted cell proliferation and migration, whereas the knockdown of CBX1 resulted in the opposite phenotypes. Mechanistically, CBX1 interacted with transcription factor HMGA2 to activate the Wnt/ß-Catenin signaling pathway. Suppression of ß-Catenin by siRNA or specific inhibitor XAV-939 markedly attenuated CBX1-mediated cell growth. Collectively, our findings indicate that CBX1 functions as an oncogene and may serve as a potential prognostic biomarker in HCC.

[Role of endoplasmic reticulum stress-induced apoptosis of trophoblasts in intrahepatic cholestasis during pregnancy].

OBJECTIVE: To investigate the role of endoplasmic reticulum stress (ERS)-induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP). METHODS: Twenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy. RESULTS: Compared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 µmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dose-dependently. Treatment with DCA at 50 µmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 µmol/L DCA for 12 h showed the presence of apoptotic bodies. CONCLUSION: The activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS-induced trophoblasts apoptosis may play a key role in the development of ICP.

UBE2S enhances the ubiquitination of p53 and exerts oncogenic activities in hepatocellular carcinoma.

Ubiquitin-conjugating enzyme E2S (UBE2S) plays pivotal roles in the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unknown. Here, we show that UBE2S is upregulated in HCC and exhibits oncogenic activities via enhancing the ubiquitination of p53. Increased expression of UBE2S was significantly correlated with higher serum AFP level, higher pathological grade, advanced TNM stage, larger tumor size, vascular invasion and unfavorable patient survivals in two independent cohorts containing a total of 845 patients with HCC. Multivariate analyses by cox regression model suggested UBE2S as an independent factor for overall survival. In vitro experiments demonstrated that UBE2S overexpression promoted, whereas UBE2S knockdown suppressed cell proliferation and migration via modulation of p53 signaling pathway. Ectopic expression of UBE2S upregulated the expression of p53 and its downstream effectors, such as p21 and Cyclin D1. Mechanistically, UBE2S enhanced the ubiquitination of p53 protein to facilitate its degradation in HCC cells. Re-expression of p53 partially attenuated the UBE2S-promoted malignant phenotypes. Collectively, our study provides compelling evidence that UBE2S is a potential prognostic factor and functions as an oncogene in HCC.

[Effect of Eletroacupuncture Intervention on Insulin Resistance, Lipid Metabolic Disorder and Expression of Hepatic SREBP-1 c and Fatty Acid Synthase Proteins in Rats with Hyperlipidemia].

OBJECTIVE: To observe the effect of electroacupuncture(EA) of "Fenglong" (ST 40) and "Sanyinjiao" (SP 6) on lipid metabolic disorder, insulin resistance (IR) and expression of sterol regulatory element blinding protein-1 (SREBP-1) c and fatty acid synthase (FAS) proteins in the liver tissue in hyperlipidemia rats with IR, so as to reveal its mechanisms underlying improvement of IR. METHODS: Forty male SD rats were randomly divided into blank control, model, medication and EA groups (n＝8 in each group). The IR model was established by feeding the rat with high-fat diet. Rats of the medication group were treated by intragastric administration of pioglitazone (10 mL/kg). For rats of the EA group, EA (2 Hz/100 Hz，1 mA) was applied to bilateral ST 40 and SP 6, once daily for 14 days. The insulin sensitivity index (ISI) was assessed by calculating 60－120 min glucose infusion rate (GIR 60－120) with euglycemic hyperinsulinemic clamp in reference to Kraegen's and colleagues' methods. Fasting blood samples (10 mL) were collected and analyzed for fasting blood glucose (FBG) using enzyme method, serum fasting insulin(FINS) using ELISA, free fatty acid(FFA) using spectrophotometry, and total triglyceride(TG) and total cholesterol(TC) employing glycerine phosphate oxidase peroxidase (GPO-PAP) assay, low density lipoprotein(LDL), high density lipoprotein(HDL) levels using combined filiter paper activity and lipase activity methods, respectively. The IR level was assessed by calculating homeostatic model assessment of insulin resistance (HOMA-IR) using the formula (FBG×FINS)/22.5. The expression levels of SREBP-1 c and FAS proteins in the liver tissue were detected by Western blot. RESULTS: Following modeling, the GIR 60－120 and serum HDL were significantly decreased(P<0.01), and the HOMA-IR, serum FBG, FINS, FFA, TG, TC and LDL, and the expression levels of hepatic SREBP-1 c and FAS proteins were significantly increased in comparison with the blank control group(P<0.01). After the intervention, the decreased GIR 60－120 and serum HDL levels were considerably up-regulated (P<0.01), and the increased FBG, FINS, FFA, TG, TC and LDL, and hepatic SREBP-1 c and FAS protein levels were notably down-regulated in both EA and medication groups relevant to the model group (P<0.05, P<0.01). No significant differences were found between the EA and medication groups in all the indexes mentioned above (P>0.05). CONCLUSION: EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in reducing the expression of SREBP-1 c and FAS proteins and in lowering the synthesis of fatty acid.

Memristive Synapses with Photoelectric Plasticity Realized in ZnO1-x/AlOy Heterojunction.

With the end of Moore's law in sight, new computing architectures are urgently needed to satisfy the increasing demands for big data processing. Neuromorphic architectures with photoelectric learning capability are good candidates for energy-efficient computing for recognition and classification tasks. In this work, artificial synapses based on the ZnO1-x/AlOy heterojunction were fabricated and the photoelectric plasticity was investigated. Versatile synaptic functions such as photoelectric short-term/long-term plasticity, paired-pulse facilitation, neuromorphic facilitation, and depression were emulated based on the inherent persistent photoconductivity and volatile resistive switching characteristics of the device. It is found that the naturally formed AlOy layer provides traps for photogenerated holes, resulting in a significant persistent photoconductivity effect. Moreover, the resistive switching can be attributed to the electron trapping/detrapping at the trapping sites in the AlOy layer.

Role of endoplasmic reticulum stress-induced apoptosis of trophoblasts in intrahepatic cholestasis during pregnancy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of endoplasmic reticulum stress (ERS)-induced trophoblast apoptosis in the development of intrahepatic cholestasis during pregnancy (ICP).</p><p><b>METHODS</b>Twenty pregnant women with ICP and 20 normal pregnant women undergoing cesarean section were enrolled in this study. The number of placenta syncytial knots in these women was determined using HE staining. The mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 were detected using RT-PCR in the placental tissues of the women and also in HTR-8/SVneo cells treated with different doses of deoxycholic acid (DCA). Caspase-3 and caspase-7 activities were also detected in DCA-treated HTR-8/SVneo cells using commercial assay kits, and the presence of apoptotic bodies in the cells were detected with electron microscopy.</p><p><b>RESULTS</b>Compared with normal placental tissues, the placenta from women with ICP showed significantly increased syncytial knots (P<0.01) and obviously enhanced mRNA expressions of GRP78, CHOP, caspase-3, and caspase-7 (P<0.05). In HTR-8/SVneo cells treated with different doses of DCA (0, 10, 50, and 100 µmol/L), the mRNA expressions of GRP78, CHOP, caspase-3 and caspase-7 were significantly increased in a dose-dependent manner (P<0.05) and the protein levels of GRP78 and CHOP were also increased dose-dependently. Treatment with DCA at 50 µmol/L for 24 h significantly upregulated caspase-3 and caspase-7 activity in the cells (P<0.05), and the cells treated with 50 µmol/L DCA for 12 h showed the presence of apoptotic bodies.</p><p><b>CONCLUSION</b>The activation of ERS and enhanced apoptosis of the trophoblasts occur in the placenta of women with ICP. DCA can significantly increase the expressions of ERS markers and thus lead to trophoblast apoptosis, suggesting that ERS-induced trophoblasts apoptosis may play a key role in the development of ICP.</p>

Research on the Diagnosis of Smith-Magenis Syndrome / 中山大学学报(医学科学版)

[Objective] We explore the diagnosis of Smith-Magenis syndrome and its clinical features of children,to raise the domestic awareness of this disease.[Methods] In this study,the child received peripheral blood chromosome microarray analysis,blood routine and urine routine,growth hormone provocation test,insulin-like growth factor Ⅰ and insulin-like growth factor binding protein Ⅲ test,cortisol (8a) test,prolactin test,adrenocorticotropic hormone test,thyroid function test,liver and kidney function test,blood biochemistry test,fasting insulin test,2-hour plasma glucose test,the antibodies and antigens test of hepatitis B.The bone age measurement and the pituitary gland MRI were also performed.We use the above figures to diagnose Smith-Magenis syndrome,assess and observe the condition of the child in Smith-Magenis syndrome.[Results] In this case,the chromosomal microarray analysis revealed a deletion of about 3.6Mb fragments in the chr17p11.2 region,including main functional gene RAI1,which was associated with Smith-Magenis syndrome.According to the clinical manifestations and the result of chromosome microarray analysis,the diagnosis of children with Smith-Magenis syndrome was made clear.[Conclusion] Genetic tests are the standard for diagnosing Smith-Magenis syndrome.When children have special facial features combined with multiple system disorders,early genetic examination is conducive to early diagnosis,and can reduce the time and economic cost.

CEP131 indicates poor prognosis and promotes cell proliferation and migration in hepatocellular carcinoma.

Centrosomal proteins have been implicated in the progression of human diseases. CEP131 plays important roles in centrosome duplication and genome stability, but its role in cancers remains largely unknown. Here, we showed that CEP131 expression was increased in hepatocellular carcinoma (HCC), compared to the paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression was closely associated with tumor size (P=0.020), tumor capsule (P=0.043), TNM stage (P=0.007) and tumor differentiation (P=0.019). Furthermore, patients with high expression of CEP131 were accompanied with worse overall and disease-free survivals in our and TCGA cohorts consisting of a total of 802 cases. The prognostic value of CEP131 was further confirmed by stratified survival analysis. Multivariate cox regression model indicated that CEP131 was an independent factor for overall survival (hazard ratio=1.762, 95% confident interval: 1.443-2.151, P<0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell lines enhanced cell proliferation and migration, whereas the knockdown of CEP131 led to the opposite phenotypes. Further studies demonstrated that CEP131 exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken together, our findings suggest CEP131 serves as a potential prognostic biomarker in HCC, and functions as an oncogene in this deadly disease.

[Expectant therapy versus curettage for retained products of conception after second trimester termination of pregnancy: analysis of outcomes and complications].

OBJECTIVE: To evaluate the prognosis and complications of expectant therapy and curettage for retained product of conception (RPOC) after second trimester termination of pregnancy (TOP). METHODS: A total of 270 patients with RPOC following second trimester TOP in Nanfang Hospital between January, 2014 and December, 2015 were included in this study. The duration of vaginal bleeding time and menstruation recovery interval were compared between patients receiving expectant therapy and curettage for RPOC, and binary logistic regression was used to assess the risk factors for complications in bivariate and multivariate analyses. RESULTS: The duration of vaginal bleeding time was significantly longer in expectant therapy group than in curettage group (P=0.005), while the menstruation recovery interval did not differ significantly between the two groups. The incidence of vaginal bleeding time for over 42 days was significantly higher in curettage group than in expectant therapy group (P=0.040), and the incidence of a menstruation recovery interval beyond 60 days was comparable between them. The incidence of complications was significantly higher in curettage group than in expectant therapy group either with adjustment of age, gravidity, parity, history of uterine surgery status, gestational age, type of indications, regimens for TOP and induction-abortion interval (OR=18.26 [95% CI: 3.57-93.42], P<0.001) or without adjustment (OR=10.60, [95% CI: 2.36-47.66], P=0.002). CONCLUSION: Expectant therapy and curettage for RPOC after second trimester TOP have comparable prognosis, but curettage is associated with a significantly higher rate of complications.

Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

Expectant therapy versus curettage for retained products of conception after second trimester termination of pregnancy: analysis of outcomes and complications / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the prognosis and complications of expectant therapy and curettage for retained product of conception (RPOC) after second trimester termination of pregnancy (TOP).</p><p><b>METHODS</b>A total of 270 patients with RPOC following second trimester TOP in Nanfang Hospital between January, 2014 and December, 2015 were included in this study. The duration of vaginal bleeding time and menstruation recovery interval were compared between patients receiving expectant therapy and curettage for RPOC, and binary logistic regression was used to assess the risk factors for complications in bivariate and multivariate analyses.</p><p><b>RESULTS</b>The duration of vaginal bleeding time was significantly longer in expectant therapy group than in curettage group (P=0.005), while the menstruation recovery interval did not differ significantly between the two groups. The incidence of vaginal bleeding time for over 42 days was significantly higher in curettage group than in expectant therapy group (P=0.040), and the incidence of a menstruation recovery interval beyond 60 days was comparable between them. The incidence of complications was significantly higher in curettage group than in expectant therapy group either with adjustment of age, gravidity, parity, history of uterine surgery status, gestational age, type of indications, regimens for TOP and induction-abortion interval (OR=18.26 [95% CI: 3.57-93.42], P<0.001) or without adjustment (OR=10.60, [95% CI: 2.36-47.66], P=0.002).</p><p><b>CONCLUSION</b>Expectant therapy and curettage for RPOC after second trimester TOP have comparable prognosis, but curettage is associated with a significantly higher rate of complications.</p>

HEY2, a target of miR-137, indicates poor outcomes and promotes cell proliferation and migration in hepatocellular carcinoma.

HEY2, a bHLH transcription factor, has been implicated in the progression of human cancers. Here, we showed that HEY2 expression was markedly increased in HCC, compared with the adjacent nontumorous tissues. High HEY2 expression was closely correlated with tumor multiplicity, tumor differentiation and TNM stage. Kaplan-Meier analyses revealed that HEY2 expression was significantly associated with poor overall and disease-free survival in a training cohort of 361 patients with HCC. The prognostic implication of HEY2 was validated in another cohort of 169 HCC patients. Multivariate Cox regression model indicated HEY2 as an independent factor for overall survival in HCC (Hazard ratio = 1.645, 95% confident interval: 1.309-2.067, P<0.001). We also demonstrated that HEY2 expression was inhibited by miR-137. In clinical samples, HEY2 expression was reversely associated to miR-137 expression. Furthermore, overexpression of HEY2 increased cell viabilities, colony formation and cell migration, whereas knockdown of HEY2 resulted in the opposite phenotypes. Collectively, our data suggest HEY2 as a promising biomarker for unfavorable outcomes and a novel therapeutic target for the clinical management of HCC.

[Acupoints Selection Exploring for Acupuncture Treatment of Insulin Resistance Based on Data Mining].

OBJECTIVE: To analyze the characteristics and rules of acupoint selection for acupuncture treatment of insulin resistance. METHODS: Data collections were conducted by searching references on acupuncture treatment of insulin resistance in PubMed, CNKI, VIP data base from 1991 to 2016, and acupuncture prescription data base for acupuncture treatment of insulin resistance was established. Data mining was applied to analyze the characteristics and rules of acupoint selection. RESULTS: A total of 64 papers were recruited, and 73 acupoints were selected in these papers. It was found that the acupoints as Zusanli (ST 36), Sanyinjiao (SP 6), Fenglong (ST 40) and Taichong (LR 3) were used with highest frequencies. All acupoints selected distributed in 13 meridians, especially Foot Yangming Stomach Meridian, Foot Taiyin Bladder Meridian, and Conception Vessel with a total frequency of 58.07%. The special acupoints including five-shu points, eight confluent points and back-shu points, accounted for 56.71%. CONCLUSIONS: This study excavated the regular acupoint selection and acupoints compatibility for acupuncture treatment in patients with insulin resistance, giving evidence based confirming and direction for acupuncture clinical treatment.

Increased Expression of CAP2 Indicates Poor Prognosis in Hepatocellular Carcinoma.

CAP2 has been suggested as a potential diagnostic biomarker for early hepatocellular carcinoma (HCC). However, its prognostic significance in HCC remains unclear. Here, we show that CAP2 expression is much higher in HCC tissues than that in paracarcinoma tissues, at both mRNA and protein levels. Data of immunohistochemistry (IHC) revealed that CAP2 was markedly up-regulated in 77.3% of HCC cases. High CAP2 expression, defined by the median score of IHC, was present in 53.3% of the patients. Kaplan-Meier analysis indicated that high CAP2 expression was associated with poor overall survival (P < .0001), disease-free survival (P = .013) and recurrence probability (P = .004) in a training cohort of 312 HCC patients. The prognostic implication of CAP2 in HCC was further confirmed in a validation cohort of 208 HCC patients and by stratified survival analysis. Multiple Cox regression analysis indicated CAP2 as an independent predictor for overall survival (hazard ratio (HR) = 1.615, 95% confidence interval: 1.345-1.938, P < .001). Collectively, we conclude that CAP2 is increased in HCC and is a novel unfavorable biomarker for prognostic prediction for patients with this deadly disease.

BLZF1 expression is of prognostic significance in hepatocellular carcinoma.

BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/ß-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan-Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697-0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC.