[Research progress on differential diagnosis of thalassemia trait and iron deficiency anemia by blood erythrocyte parameters].

Thalassemia trait is an autosomal recessive genetic disease, which is a hemolytic anemia caused by disturbance of erythrocyte hemoglobin production caused by gene mutation or deletion. Iron deficiency anemia is caused by a lack of iron in the body due to an imbalance between the demand and supply of iron. The laboratory manifestations of both are microcytic hypochromic anemia, but the treatment schemes are completely different, and it is difficult to distinguish them from the results of blood count. Erythrocyte parameters can be used to establish a formula or model to differentiate them, which can achieve the purpose of early screening, early diagnosis and early treatment,preventing the occurrence of severe anemia and providing a scientific basis for the thalassemia and iron deficiency anemia prevention. This article will review the research progress of using erythrocyte parameters to distinguish thalassemia trait with iron deficiency anemia.

[Analysis of dynamic functional connectivity states and influencing factors of brain network in male patients with obstructive sleep apnea].

Objective: To analyze dynamic functional connectivity (dFNC) states and influencing factors of brain network in male patients with obstructive sleep apnea (OSA). Methods: A total of 111 male patients diagnosed with obstructive sleep apnea or presenting with simple snoring, who visited the Sleep Clinic at the Second Affiliated Hospital of Soochow University between August 2020 and December 2021, were prospectively selected for this study. General information was collected, and polysomnography (PSG) was performed. Based on the oxygen desaturation index (ODI), the participants were divided into three groups: primary snoring group (ODI<5 events/hour, n=34), mild to moderate OSA group (5 events/hour≤ODI<30 events/hour, n=43), and sever OSA group (ODI≥30 events/hour, n=34). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Resting-state functional magnetic resonance imaging (fMRI) data were collected and preprocessed. dFNC matrices were constructed using a sliding time window approach. The number of dFNC states was determined using k-means clustering analysis. Three parameters, namely, fractional time (FT), mean dwell time (MDT), and number of transitions (NT), were used to characterize the temporal properties of dFNC states. Differences in the temporal properties of dFNC states among the groups were compared. The correlations between temporal properties and PSG parameters, as well as MoCA and ESS scores, were further analyzed. Multiple stepwise linear regression analysis was performed to identify the influencing factors of the temporal properties of dFNC states. Results: The age of the patients was (40.2±8.6) years (range: 25-65 years). There were no significant differences in age, smoking history and alcohol history, and MoCA scores among the three groups (all P>0.05). Three dFNC states were extracted through k-means clustering analysis: state 1, characterized by strong connections within the visual and sensorimotor networks with a frequency of 31.7% (4 611/14 541); state 2, characterized by strong connections within the default mode network, attention network, and other cognitive networks, with the lowest frequency of 22.1% (3 213/14 541); state 3, characterized by weaker connections across the whole brain, with the highest frequency of 46.2% (6 717/14 541). The FT [0.28 (0.05, 0.35) vs 0.39 (0.26, 0.53)] and MDT [8.20 (4.35, 12.54) vs 11.68 (8.50, 16.69)] of state 2 in the sever OSA group were lower than those in the primary snoring group (both P<0.05), while there were no significant differences in the temporal properties of states 1 and 3 among the three groups (all P>0.05). The FT and MDT of state 2 were correlated with body mass index (BMI), apnea-hypopnea index (AHI), ODI, and minimum oxygen saturation (MinSaO2) (FT: r values were -0.218, -0.230, -0.249, 0.198, respectively; MDT: r values were 0.269, -0.253, -0.265, 0.209, respectively; all P<0.05). There were no significant correlations between the temporal properties and MoCA or ESS scores (all P>0.05). ODI was found to be an influencing factor for the temporal properties of state 2 (FT: ß=-0.225, 95%CI:-0.227 to -0.223; MDT: ß=-0.241, 95%CI:-0.289 to -0.195). Conclusions: Male patients with OSA exhibit alterations in specific temporal properties of brain network dynamic functional connectivity, which are associated with nocturnal oxygen parameters. This may be one of the mechanisms underlying brain functional damage in patients with OSA.

[Epidemiological trend of early-onset gastric cancer and late-onset gastric cancer in China from 2000 to 2019].

Objective: In order to understand the changing trends of gastric cancer incidence and mortality in early-onset and late-onset in China from 2000 to 2019. Methods: The Global Burden of Disease research data was collected, and Excel and R 4.2.1 softwares were used to examine the incidence rate, mortality rate, and disability-adjusted life years (DALY) of Chinese people from 2000 to 2019, with a focus on gender, age, and year. Results: In 2019, the crude incidence rates were 7.06/100 000 (95%UI: 6.63/100 000-7.59/100 000) and 114.52/100 000 (95%UI: 108.79/100 000-121.63/100 000) for early- and late-onset gastric cancer, respectively. The crude mortality rate for early-onset gastric cancer was 3.29/100 000 (95%UI: 3.11/100 000- 3.50/100 000), while the crude mortality rate for late-onset gastric cancer was 81.88/100 000 (95%UI: 78.15/100 000-86.04/100 000). Additionally, the crude DALY rates for these two types of gastric cancer were 156.48/100 000 (95%UI: 148.82/100 000-165.84/100 000) and 1 750.13/100 000 (95%UI: 1 661.21/100 000-1 852.99/100 000). The standardized incidence of early-onset gastric cancer decreased from 5.49/100 000 in 2000 to 4.76/100 000 in 2019, and that of late-onset gastric cancer decreased from 143.45/100 000 in 2000 to 123.02/100 000 in 2019.The standardized mortality rate of early-onset gastric cancer decreased from 4.16/100 000 in 2000 to 2.18/100 000 in 2019, and that of late-onset gastric cancer decreased from 140.82/100 000 in 2000 to 91.49/100 000 in 2019. The standardized DALY rate for early-onset gastric cancer in 2019 was 105.87/100 000 (95%UI: 87.98/100 000 -125.60/100 000), lower than 198.84/100 000 (95%UI: 179.47/100 000- 219.83/100 000) in 2000. The standardized DALY rate for late onset gastric cancer in 2019 was 1 821.11/100 000 (95%UI: 1 509.42/100 000-2 158.53/100 000), lower than 2 932.52/100 000 (95%UI: 2 665.92/100 000-3 252.60/100 000) in 2000. Conclusions: The standardized mortality rate of early-onset gastric cancer in China showed a decreasing trend from 2000 to 2019. The standardized mortality rate of late onset gastric cancer showed a trend of first increasing and then decreasing. Notably, the incidence, mortality, and DALY of late-onset gastric cancer were significantly higher than those of early-onset gastric cancer during this period. Additionally, male incidence, mortality, and crude DALY rates were higher than female.

[The effect of strengthening nutrition education in the second trimester on the basis of the first trimester on blood glucose].

Objective: To explore the effect of strengthening individualized nutrition education in the second trimester based on first trimester on blood glucose. Methods: A retrospective study was conducted on 398 pregnant women aged (31.79±3.48) (23-41) years old who underwent an oral glucose tolerance test (OGTT) from October 2021 to December 2022 at Beijing Tsinghua Changgung Hospital. They were divided into two groups according to whether the women were re-visited in second trimester or not. The routine group consisted of 205 pregnant women aged between 24 and 41 (31.49±3.36) years old who only received the first trimester nutrition education and the strengthening group consisted of 193 pregnant women aged (31.92±3.97) (23-41) years old who received both the first and second trimester nutrition education. Then according to pre pregnancy body mass index (BMI), they were divided into normal (18.5 kg/m2≤BMI<24 kg/m2) and overweight (24 kg/m2≤BMI<28 kg/m2). The OGTT blood glucose level, the positive rate of gestational diabetes (GDM) and the weight gain during pregnancy were compared between the two groups with different BMI, in order to analyze the effect of strengthening nutrition education in the second trimester of pregnancy on blood glucose. Results: The differences between the two groups were not statistically significant in terms of the pregnant women's age, proportion of pregnant women aged≥35, proportion of pre-pregnancy BMI and overweight, parity and early pregnancy blood glucose (all P>0.05). The blood glucose levels of OGTT at 0, 1, and 2 hour were (4.57±0.37), (8.41±1.70), and (7.28±1.51) mmol/L, respectively, lower than those in the routine group [(4.74±0.48), (9.44±1.55), and (8.27±1.58) mmol/L, respectively, all P<0.001]. The positive rate of GDM in the strengthening group was 35.23% (68/193), which was lower than that in the routine group (91.71%, 188/205) (P<0.001). After the BMI stratification, the OGTT blood glucose levels and the positive rate of GDM in the strengthening group were still lower than those in the routine group (all P<0.05). The weight gain with normal BMI in the early pregnancy in routine group was higher than that in the strengthening group (P=0.003), but there was no significant statistical difference in weight gain of overweight pregnant women at different gestational weeks (all P>0.05). Conclusion: Strengthening a nutrition education about second trimester for pregnant women in the early stages of pregnancy can effectively improve blood glucose levels and reduce the positive rate of GDM.

[The value of machine learning models based on biparametric MRI for diagnosis of prostate cancer and clinically significant prostate cancer].

Objective: To evaluate the value of machine learning (ML) models based on biparametric magnetic resonance imaging (bpMRI) for diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). Methods: A total of 1 368 patients, aged from 30 to 92 (69.4±8.2) years, from 3 tertiary medical centers in Jiangsu Province were retrospectively collected from May 2015 to December 2020, including 412 cases of csPCa, 242 cases of clinically insignificant prostate cancer (ciPCa) and 714 cases of benign prostate lesions. The data of center 1 and center 2 were randomly divided into training cohort and internal testing cohort at a ratio of 7∶3 by random number sampling without replacement using Python Random package, and the data of center 3 were used as the independent external testing cohort. The training cohort includs 243 cases of csPCa, 135 cases of ciPCa and 384 cases of benign lesions, the internal testing cohort includs 104 cases of csPCa, 58 cases of ciPCa and 165 cases of benign lesions, and the external testing cohort includs 65 cases of csPCa, 49 cases of ciPCa and 165 cases of benign lesions. The radiomics features were extracted on T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient map, and optimal radiomics features were selected by using Pearson correlation coefficient method and analysis of variance. The ML models were built using two ML algorithms, including support vector machine and random forest (RF) and were further tested in the internal testing cohort and external testing cohort. Finally, the PI-RADS scores evaluated by the radiologists were adjusted by the ML models which had superior diagnostic performance, namely adjusted PI-RADS. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the ML models and PI-RADS. DeLong test was used to compare the areas under curve (AUC) of models with those of PI-RADS. Results: For PCa diagnosis, in internal testing cohort, the AUC of ML model using RF algorithm and PI-RADS were 0.869 (95%CI: 0.830-0.908) and 0.874 (95%CI: 0.836-0.913), respectively, and the difference between the model and PI-RADS did not reach to the statistical significance (P=0.793). In the external testing cohort, the AUC of model and PI-RADS were 0.845 (95%CI: 0.794-0.897) and 0.915 (95%CI: 0.880-0.951), respectively, and the difference was statistically significant (P=0.01). For csPCa diagnosis, the AUC of ML model using RF algorithm and PI-RADS were 0.874 (95%CI: 0.834-0.914) and 0.892 (95%CI: 0.857-0.927), respectively, in internal testing cohort, and the difference between the model and PI-RADS was not statistically significant (P=0.341). In the external testing cohort, the AUC of model and PI-RADS were 0.876 (95%CI: 0.831-0.920) and 0.884 (95%CI: 0.841-0.926), respectively, and the difference between the model and PI-RADS was not statistically significant (P=0.704). When PI-RADS assessment was adjusted with the assistance of ML models, the specificities increased from 63.0% to 80.0% in the internal testing cohort and from 92.7% to 93.3% in the external test group in diagnosing PCa. In diagnosing csPCa, the specificities increased from 52.5% to 72.6% in the internal testing cohort and from 75.2% to 79.9% in the external testing cohort. Conclusions: The ML models based on bpMRI showed comparable diagnostic performance to PI-RADS assessed by senior radiologists and achieved good generalization ability in both diagnosing PCa and csPCa. The specificities of the PI-RADS were improved by ML models.

The role of lymphocyte count in the early diagnosis of surgical site infection following posterior lumbar fusion.

OBJECTIVE: This study aimed to explore the early diagnostic value of lymphocyte count in the early diagnosis of surgical site infection (SSI) following posterior lumbar fusion. PATIENTS AND METHODS: In this study, we retrospectively analyzed the data from a total of 37 patients with lumbar SSI from Guizhou  Province Orthopaedic Hospital and Nanyang Central Hospital, 2008.1-2018.11, and 104 patients without SSI. We analyzed the C-reactive protein (CRP) level, white blood cell count (WBC) and differential count before instrumented lumbar fusion at 3 and 7 days postoperatively. The significance of the differences was evaluated by one-way ANOVA, followed by Fisher's test. The parameters mentioned above were analyzed on postoperative days 3 and 7 using the receiver operating characteristic curve and the area under the curve (AUC). Furthermore, the analyses were conducted by SPSS 22.0 software. RESULTS: The lymphocyte count in the SSI group on postoperative day 3 was significantly lower than that in the no-SSI group after surgery (p=0.000). According to the ROC curve analysis of related parameters on postoperative day 3, the AUC value of lymphocytes (0.840) was significantly larger than the AUC value of C-reactive protein (0.749). CONCLUSIONS: The lymphocyte count and C-reactive protein level on postoperative day 3 are reliable predictors of infection.

[Advances in tumor regression patterns and safe distance of distal resection margin after neoadjuvant therapy for rectal cancer].

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.

[Correlation between first tarsometatarsal joint sagittal mobility and hallux valgus combined with transfer metatarsalgia].

Objective: To investigate the correlation between the first tarsometatarsal joint (TMT1) sagittal mobility and hallux valgus (HV) combined with transfer metatarsalgia (TM). Methods: The weight-bearing CT (WBCT) imaging data of 111 HV patients (167 feet) who were treated at the Foot and Ankle Surgery Center, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2018 to January 2020 were retrospectively analyzed. The patients underwent PedCAT WBCT scans of both feet, and the hallux valgus angle (HVA), intermetatarsal angle (IMA), plantar distance (PD), medial cuneiform-first metatarsal angle (CMA) and metatarsal protrusion distance (MPD) were measured using CubeVue software. PD and CMA were signs of TMT1 instability. Visual analogue scale (VAS) and foot and ankle ability measures (FAAM) scores were obtained. The patients were divided into TM group and non-TM group according to the presence of metatarsalgia. The TM group and the non-TM group were compared in terms of HVA, IMA, PD, CMA, MPD, VAS and FAAM. Correlations between PD, CMA and HVA, IMA, VAS, FAAM were analyzed using Spearman correlation. Results: Total of 111 cases were included in this study, there were 35 males and 76 females with a mean age of (57.7±14.1) years. The average values of HVA (37.9°±8.6°), IMA (17.9°±2.6°), CMA (2.1°±0.3°) and PD [(1.8±0.4) mm] in TM group were all significantly higher than those in the non-TM group [HVA (32.5°±9.1°), IMA (15.1°±3.4°), CMA (1.7°±0.3°) and PD (1.6±0.2) mm] (All P<0.001). There was no significant difference in MPD between the two groups (P=0.580). The TM group demonstrated a higher VAS score when compared with the non-TM group (P<0.001). The FAAM score of the TM group (54.1±11.8) was significantly lower than that in the non-TM group (66.2±11.4) (P<0.001). The results of Spearman correlation analysis showed that there was no correlation between PD and HVA, IMA and VAS score. There was a negative correlation between PD, CMA and FAAM score, and the difference was statistically significant (rs=-0.637, -0.254, both P<0.001); CMA was positively correlated with HVA, IMA, and VAS score (rs=0.603, 0.971, 0.269, all P<0.001). Conclusions: WBCT is helpful for the diagnosis of TMT1 sagittal instability. The severity of TMT1 sagittal instability is positively correlated with hallux valgus and TM. The TMT1 instability may play an important role in the pathogenesis of hallux valgus.

Molecular typing and epidemiology profiles of human adenovirus infection among children with severe acute respiratory infection in Huzhou, China.

Human adenoviruses (HAdVs) are prevalent worldwide and are a common cause of respiratory tract infection in people of all ages. However, little is known about HAdV infection among children with severe acute respiratory infection (SARI). The present study retrospectively analysed the molecular typing and epidemiological characteristics of HAdV-positive samples from children with SARI from January 2017 to December 2021 in Huzhou. The results showed that 89 (8·27%) of 1078 SARI paediatric patients were positive for HAdVs. Children <5 years of age accounted for 87·64% of the positive cases. The peak seasons for HAdV infection were the first quarter and the fourth quarter. In addition, HAdV-B and HAdV-C were circulating among paediatric patients with SARI, of which the B3 genotype (n = 30, 51·72%) was the most prevalent and was detected every year, indicating that B3 is the main epidemic strain in the Huzhou area, followed by C1 (n = 9, 15·52%), C2 (n = 7, 12·07%) and B7 (n = 5, 8·62%). These findings provide a benchmark for future epidemiology and prevention strategies for HAdVs.

[A prospective cohort study on the clinical value of pelvic peritoneal reconstruction in laparoscopic anterior resection for middle and low rectal cancer].

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

The role of Dock2 on macrophage migration and functions during Citrobacter rodentium infection.

Dedicator of cytokinesis 2 (Dock2), an atypical guanine exchange factor, is specifically expressed on immune cells and mediates cell adhesion and migration by activating Rac and regulates actin cytoskeleton remodeling. It plays a crucial role in the migration, formation of immune synapses, cell proliferation, activation of T and B lymphocytes and chemotaxis of pDCs and neutrophils. However, in-vivo physiological functions of Dock2 have been relatively seldom studied. Our previous studies showed that Dock2-/- mice were highly susceptible to colitis induced by Citrobacter rodentium infection, and in early infection, Dock2-/- mice had defects in macrophage migration. However, the specific roles of Dock2 in the migration and functions of macrophages are not clear. In this study, we found that the expression of chemokines such as chemokine (C-C motif) ligand (CCL)4 and CCL5 and chemokine receptors such as chemokine (C-C motif) receptor (CCR)4 and CCR5 in bone marrow-derived macrophages (BMDM) of Dock2-/- mice decreased after infection, which were supported by the in-vivo infection experimental results; the Transwell experiment results showed that Dock2-/- BMDM had a defect in chemotaxis. The bacterial phagocytic and bactericidal experiment results also showed that Dock2-/- BMDM had the defects of bacterial phagocytosis and killing. Furthermore, the adoptive transfer of wild-type BMDM alleviated the susceptibility of Dock2-/- mice to C. rodentium infection. Our results show that Dock2 affects migration and phagocytic and bactericidal ability of macrophages by regulating the expression of chemokines, chemokine receptors and their responses to chemokine stimulation, thus playing an essential role in the host defense against enteric bacterial infection.

[Discussion on the mechanism of anal sphincter insufficiency caused by radiotherapy in patients with rectal cancer].

At present, radiotherapy as an auxiliary treatment for rectal cancer is widely used in clinic. Although radiotherapy has significant effect on reducing tumor stage, improving anus preservation rate and less tumor recurrence, radiotherapy will damage the anal function and seriously affect the quality of life of patients. Anal sphincter plays an important role in anal function. There are three main damage effects of radiotherapy on anal sphincter: first, the increased deposition of collagen in internal anal sphincter (IAS); second, the destroyed ultrastructure of external anal sphincter (EAS); third, degenerative lesions of the perianal nerve. This article reviews these three points, in order to provide a certain theoretical basis for how to reduce the incidence of anal dysfunction caused by radiotherapy.

Curcumin exerts protective effect on PC12 cells against lidocaine-induced cytotoxicity by suppressing the formation of NLRP3 inflammasome.

OBJECTIVE: To explore the protective effect of curcumin on lidocaine-insulted PC12 cells. MATERIALS AND METHODS: We first treated PC12 cells with different doses of lidocaine, and then treated the cells with curcumin or Nod-like receptor pyrin domain3 (NLRP3) inhibitor (MCC950). Subsequently, the cell viability, apoptosis, reactive oxygen species (ROS) production and NLRP3 inflammasome were detected by cell counting kit-8 (CCK8), Annexin V/PI staining, FCM and Western blot analysis, respectively, and the level of IL-1ß in PC12 cells was determined by an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Lidocaine inhibited the viability of PC12 cells, and it induced cell apoptosis, promoted ROS release and activated NLRP3 inflammasome in PC12 cells, but its effects were reversed by the treatment of curcumin. Moreover, NLRP3 over-expression also induced cytotoxicity in PC12 cells, which was also rescued by the treatment of curcumin. CONCLUSIONS: Our study indicates that curcumin exerts protective effect against lidocaine-induced cytotoxicity on PC12 cells by suppressing the activity of NLRP3 inflammasome, which provides new ideas on screening natural product for neurological damage therapy.

Effect of GATA4 gene methylation on proliferation and apoptosis of SGC-7901 gastric cancer cells.

Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. GATA4 has been previously reported to exhibit functions in GC. In this study, we aimed to investigate the effect of GATA4 gene methylation on GC progression. Methylation-Sensitive High-Resolution Melting was used to detect the methylation of GATA4 promoter region in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cells. The relationship between GATA4 methylation level and clinical characteristics of GC patients was analyzed. GATA4 levels in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cell lines were detected, and gain-of-function was performed to investigate the role of GATA4 in GC. si-GATA4 was transfected into GES-1 cells to observe the changes of various indicators. RNA-seq detected the differentially expressed genes in SGC-7901 cells overexpressing GATA4, and western blot analysis verified their expression. GATA4 methylation rate was increased in GC tissues, and GATA4 promoter was abnormally methylated in GC cells. GATA4 methylation rate in GC tissues was related to lymph node metastasis, differentiation degree and clinical stage of GC patients. Lower expressed GATA4 was observed in GC tissues and cells. Cell proliferation rate decreased and cell apoptosis rate increased in SGC-7901 cells overexpressing GATA4. Transfecting si-GATA4 into GES-1 cells led to increased proliferation, inhibited apoptosis, and restoration of GATA4 led to decreased APC and GSK3ß levels. In conclusion, restoration of GATA4 caused by 5-Aza treatment can inhibit the proliferation and promote apoptosis of GC cells possibly via Wnt/ß-catenin signaling pathway. This study may offer new sight for GC treatment.

Relationship between inflammatory factors and arrhythmia and heart rate variability in OSAS patients.

OBJECTIVE: Obstructive Sleep Apnea Syndrome (OSAS) is a disorder characterized by recurrent upper airway obstruction, apnea, and hypopnea, associated with decreased oxygen saturation and disturbed sleep structure during sleep. It was found that OSAS was associated with a variety of arrhythmia and conduction disorders, but the relationship between multiple types of arrhythmia and the severity of OSAS, and its possible mechanism remain unclear. The purpose of this study was to observe the main types of arrhythmia and the condition of heart rate variability (HRV) in patients with OSAS, to detect the levels of multiple inflammatory factors in serum of OSAS patients, and to observe the correlation between polysomnographic parameters or inflammatory factors, and arrhythmia or HRV, as well as its possible mechanisms. PATIENTS AND METHODS: 141 patients with suspected OSAS were collected in the Second Affiliated Hospital of Soochow University and Xinghua People's Hospital from February 2016 to February 2018. According to the sleep apnea hypopnea index (AHI), they were divided into control group (AHI <5, n = 34), mild-moderate OSAS group (5≤ AHI <30, n = 48), and severe OSAS group (AHI ≥30, n = 59). Clinical data such as gender and age were collected. All patients completed polysomnography (PSG), 24-hour Holter monitoring and blood routine, biochemical indexes and serum hs-CRP, TNF-α, IL-6, and IL-1ß testing. The indicators in the three groups were compared, and the correlation between PSG parameters, HRV and inflammatory biomarkers was investigated. RESULTS: Compared with control group, there were significant differences in age, sex ratio, BMI, uric acid, TC, and TG in the mild-moderate OSAS group (p<0.05), and in age, sex ratio, BMI, red blood cell count, hemoglobin, hematocrit, uric acid, FBS, TC, TG, LDL, and HDL in severe OSAS group (p<0.05). There were significant differences in gender ratio, BMI, red blood cell count, hemoglobin, hematocrit, uric acid, FBS, TC, TG, LDL, and HDL between mild-moderate OSAS group and severe OSAS group (p<0.05). Heart rate variability (HRV) parameters include SDNN, SDNN index, RMSSD, PNN50, LF, HF, and LF/HF. SDNN, PNN50, and HF in severe OSAS group and mild-moderate OSAS group were significantly lower than those in control group (p<0.05). LF/HF was significantly higher than that of control group (p<0.05). There was a significant difference in PNN50, HF, and LF/HF between severe OSAS group and mild-moderate OSAS group (p<0.05). In terms of inflammation, serum hs-CRP was significantly higher in mild-moderate OSAS group and severe OSAS group than that in control group (p<0.05). Serum IL-1ß was significantly higher in mild-moderate OSAS group than that in severe OSAS group (p<0.05). There was no significant difference in other indicators (p>0.05). There was a significant positive correlation between hs-CRP and oxygen reduction index (ODI) (r=0.209, p=0.013) and a significant negative correlation with PNN50 (r=-0.188, p=0.025). There is no significant correlation between other indicators. CONCLUSIONS: Systemic inflammatory reactions existed in patients with OSAS. With the increase of OSAS, inflammation was aggravated, especially serum hs-CRP. Hs-CRP was significantly and negatively correlated with PNN50 and positively correlated with ODI. The results suggested that the inflammatory response was involved in the occurrence of heart rate variability in OSAS patients.

[Application of the superior thyroid artery peak systolic velocity in differentiating Graves' disease from autoimmune thyroiditis].

Objective: To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis. Methods: A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People's Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves' disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD. Results: STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95%CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT(4)) (ß=0.371, 95%CI 0.005-0.010, P<0.001) and TRAb (ß=0.138, 95%CI 0.001-0.014, P=0.035) were positively associated with STA-PSV. Conclusions: The STA-PSV is positively associated with FT(4) and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

[Current consensus and controversy in neoadjuvant therapy for pancreatic cancer].

Pancreatic cancer is malignant and has a poor prognosis.At present, the treatment mode has changed from "Surgery First" to systemic therapy under multi-disciplinary team, but surgical resection is still the only way to cure pancreatic cancer. In systemic treatment of pancreatic cancer, the effect of postoperative adjuvant therapy is significant, and preoperative neoadjuvant therapy has gradually attracted widespread attention. Neoadjuvant therapy can improve the rate of R0 resection in patients with pancreatic cancer.There is a consensus on neoadjuvant therapy for patients who with borderline resectable and locally advanced, but for the patients who with resectable remains controversial.

[Ultrasound screening and follow-up study of congenital anomalies of the kidney and urinary tract in neonates].

OBJECTIVE: To investigate the incidence of congenital anomalies of the kidney and urinary tract (CAKUT) in neonates, and to evaluate the value of urinary ultrasound screening in the early postnatal period. METHODS: The neonates born or treated in Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University between January 2016 and December 2018 accepted the urinary ultrasound screening, and the neonates with problem were followed up. In the meanwhile, the maternal pregnancy data were analyzed to screen out the risk factors associated with the onset of CAKUT. RESULTS: (1)A total of 2 655 neonates were screened by ultrasonography, of whom 82 neonates had been diagnosed with CAKUT (male: 60 cases, female: 22 cases), the positive rate was 3.1% (82/2 655). There were 66 cases of hydronephrosis, 6 cases of duplicate kidney, 2 cases of multiple renal cysts, 2 cases of renal cystic dysplasia, 1 case of medullary sponge kidney, 3 cases of small kidney, 1 case of isolated kidney, and 1 case of horseshoe kidney. (2)Of the 66 children with hydronephrosis, 4 cases were lost to the follow-up; 8 cases were followed for less than six months with no significant changes found, and still in the follow-up observation; 54 cases were followed up for 1 year, among which 32 cases were returned to normal within 1 year, 3 cases were alleviated, 7 cases were aggravated, and 12 cases were unchanged. One case underwent surgery for repeated urinary tract infections and decreased renal function. (3) Abnormal fetal urinary ultrasound in the late pregnancy was found to be the most common in the high risk factors of CAKUT. There were 44 high-risk newborns with abnormal fetal urinary ultrasound, and 35 cases of CAKUT were diagnosed after birth. The incidence rate was 79.5%(35/44). (4)Among the 2 655 newborns screened, 2 611 newborns had normal antenatal urinary ultrasonography. Among these neonates with normal urinary ultrasound during pregnancy,47 cases of CAKUT were diagnosed after birth, with an incidence of 1.8% (47/2 611). CONCLUSION: The most common CAKUT in neonates is hydronephrosis and most cases with hydronephrosis had a good prognosis, but they should be followed up regularly. Urinary ultrasound screening for neonates, especially those high-risk neonates with abnormal fetal urinary ultrasound, has important clinical implications for the early detection of CAKUT.

[The expression of VHL/HIF signaling pathway in the erythroid progenitor cells with chronic mountain sickness].

Objective: To investigate the expression and interaction of VHL/HIF-α pathways including HIF-1α, HIF-2α as well as VHL in erythroid progenitor cells of bone marrow from chronic mountain sickness (CMS) patients. Methods: A total of 25 patients with CMS and 21 healthy controls were recruited for this study. The CD71(+)CD235a(+) cells in bone marrow mononuclear cells, marked as erythroid progenitor cells, were isolated using MACS separation technology. The expression levels of HIF-1α, HIF-2α and VHL in erythroid progenitor cells were detected by Western blotting and real-time fluorescence quantitative PCR. Results: The mRNA levels of HIF-2α were higher in erythroid progenitor cells of CMS than in healthy controls [1.68 (0.81, 2.22) vs 0.98 (0.60, 1.19), P<0.05], while HIF-1α and VHL mRNA levels were similar between the two groups (P>0.05). Spearman analyses indicated that HIF-2α mRNA was positively associated with hemoglobin (Hb) levels in the erythroid progenitor cells of CMS (ρ=0.504, P<0.05). Furthermore, the mRNA level of HIF-2α was correlated with the mRNA level of VHL in the erythroid progenitor cells of CMS (ρ=0.647, P<0.05).The protein levels of HIF-2α in the erythroid progenitor cells of CMS were higher than that of healthy controls [0.94(0.68, 3.30) vs 0.59(0.30, 0.88), P<0.05], but the protein levels of HIF-1α and VHL were similar between the two groups (P>0.05). Conclusions: The abnormal increased expression of HIF-2α in the erythroid progenitor cells of CMS patients leads to the abnormal expression of hypoxia sensitive genes downstream, participating in the occurrence and development of CMS.

Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats.

OBJECTIVE: To investigate the expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer (DFU) and its effect on angiogenesis in DFU rats. METHODS: The serum levels of miR-217, HIF-1α and VEGF were detected in DFU and simple diabetes mellitus (DM) patients, and healthy controls. DFU rat models were established and treated with miR-217 inhibitors and/or HIF-1α siRNA. The ulcer healing of DFU rats was observed. Besides, ELISA method was performed to detect the serum level of HIF-1α, VEGF and inflammatory factors, immunohistochemical (IHC) method to test the micro-vessel density (MVD), as well as qRT-PCR and Western blot to determine expressions of miR-217, HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 in tissues. RESULTS: The serum levels of miR-217 were up-regulated while HIF-1α and VEGF were down-regulated in DFU patients and rats when compared with DM and healthy controls (all P < 0.05). Dual-luciferase reporter gene assay confirmed that HIF-1α was the direct target gene of miR-217. DFU rats treated with miR-217 inhibitors had decreased foot ulcer area and accelerated ulcer healing, with significantly reduced inflammatory factors (IL-1ß, TNF-α and IL-6), as well as elevated HIF-1α and VEGF (all P < 0.05); meanwhile, they remarkably increased the MVD in foot dorsum wound tissues and the protein expressions of HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 (all P < 0.05). CONCLUSION: Inhibiting miR-217 could up-regulate HIF-1α/VEGF pathway to promote angiogenesis and ameliorate inflammation of DFU rats, thereby effectively advancing the healing of ulcerated area.