[Introduction to the 9th edition of TNM classification for lung cancer].

Lung cancer is the second commonly diagnosed cancer and remained the leading cause of cancer-related death, with an estimated 1.8 million deaths in 2020. The identification of driver gene mutation and administration of corresponding tyrosine kinase inhibitor have improved overall survival and quality of life in advanced lung cancer patients. Check point inhibitor has revolutionized treatment strategy of driver gene negative advanced NSCLC patients. TNM staging system is the most widely used classification method, providing an international common language during academic communication and important tool for predicting prognosis and subsequent treatment decision making. Accumulating knowledge about prognostic factors in lung cancer promotes the update of TNM classification. In the World Conference on Lung Cancer (WCLC) held in Singapore, September, 2023, International Association for Study of Lung Cancer (IASLC) released the forthcoming 9th edition of TNM classification for lung cancer, which is supposed to be adopted at January, 2024. The manuscript discussed the history, data resource and limitation of the TNM staging system.

[Analysis of the therapeutic effect of aspiration thrombectomy for early carotid stent thrombosis].

Objective: To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS). Methods: This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected. Results: The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions: Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Dung treated by high-temperature composting is an optimal bedding material for suckling calves according to analyses of microbial composition, growth performance, health status, and behavior.

Bedding materials are important for suckling buffalo calves. Treated dung has been used as a bedding material for dairy cows but the lack of an appropriate safety assessment limits its application. In this study, we evaluated the feasibility of treated dung (TD) as a bedding material for suckling calves by comparing TD with rice husk (RH) and rice straw (RS) bedding materials. The TD was prepared through high-temperature composting by Bacillus subtilis. Thirty-three newborn suckling buffalo calves (Bubalus bubalis, 40.06 ± 5.79 kg) were randomly divided into 3 bedding material groups (TD, RH, and RS) and bedded with 1 of the 3 bedding materials for 60 d. We compared cost, moisture content, bacterial counts, and microbial composition of the 3 bedding materials, and investigated growth performance, health status, behavior, rumen fermentation, and blood parameters of bedded calves. The results showed that TD contained the fewest gram-negative bacteria and coliforms on d 1 and 30 and the lowest relative abundance of Staphylococcus throughout the experiment. The RH and TD bedding materials had the lowest cost. Calves in the TD and RS groups showed a higher dry matter intake, and final body weight and average daily gain in the TD and RS groups tended to be higher than in the RH group. Calves in the TD and RS groups had a lower disease incidence (diarrhea and fever), fewer antibiotic treatments, and lower fecal score than calves in the RH group. Higher contents of IgG, IgA, and IgM were observed in calves of the TD and RS groups than in calves of the RH group on d 10, indicating higher immune ability in TD and RS groups. Furthermore, TD bedding increased the butyric acid content in the calf's rumen, whereas RS bedding increased the acetate content, which might be attributed to the longer time and higher frequency of eating bedding material in the RS group. Considering all of the above indicators, we concluded that TD is the optimal bedding material for calves based on economics, bacterial count, microbial diversity, growth performance, and health status. Our findings provide a valuable reference for bedding material choice and calf farming.

miR-199-3p suppresses cellular migration and viability and promotes progesterone production in goose ovarian follicles before selection through regulating ITGB8 and other ECM-related genes.

1. The extracellular matrix (ECM) constitutes the basal lamina and the area between follicular cells. Remodelling the ECM is believed to be a key event in follicular development, especially during selection, and plays an important role in cell migration, survival, and steroidogenesis. miR-199-3p is differentially expressed in the goose granulosa layer during follicular selection and is reported to play a primary role in inhibiting cell migration and invasion. Nevertheless, the effect of miR-199-3p on ovarian follicles and its role in follicular cellular migration is not understood.2. In this study, qRT-PCR assays revealed that miR-199-3p was differentially expressed in the granulosa layer from goose ovarian follicles before and after follicular selection. Additionally, miR-199-3p overexpression in cultured granulosa cells (GCs) from goose pre-hierarchical follicles significantly suppressed cell viability and migration. It elevated the concentration of progesterone and the expression of key progesterone production genes. Furthermore, miR-199-3p overexpression in the GCs of goose pre-hierarchical follicles inhibited the expression of ECM-related genes (ITGB8, MMP9 and MMP15) yet promoted the expression of another two ECM-related genes (COL4A1 and LAMA1). Finally, dual-fluorescence reporter experiments on 293T cells established the direct targeting of ECM gene ITGB8 by miR-199-3p.3. In conclusion, miR-199-3p may participate in granulosa cell migration, viability, and steroidogenesis in goose ovarian follicles before selection by modulating ITGB8 and other ECM-related genes.

[Clinical diagnosis and treatment of multiple pulmonary nodules].

CT screening has markedly reduced the lung cancer mortality in high-risk population and increased the detection of early-stage pulmonary neoplasms, including multiple pulmonary nodules, especially those with a ground-glass appearance on CT. Multiple primary lung cancer (MPLC) constitutes a specific subtype of lung cancer with indolent biological behaviors, which is predominantly early-stage adenocarcinoma. Although MPLC progresses slowly with rare lymphatic metastasis, existence of synchronous lesions and distributed location of these nodules still pose difficulty for the management of such patients. One single operation is usually insufficient to eradicate all neoplastic lesions, whereas repeated surgical procedures bring about another dilemma: whether clinical benefits of surgical treatment outweigh loss of pulmonary function following multiple operations. Therefore, despite the anxiety for treatment among MPLC patients, whether and how to treat the patient should be assessed meticulously. Currently there is a heated discussion upon the timing of clinical intervention, operation mode and the application of local therapy in MPLC. Based on clinical experience of our multiple disciplinary team, we have summarized and commented on the evaluation, surgical treatment, non-surgical local treatment, targeted therapy and immunotherapy of MPLC in this article to provide further insight into this field.

[Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study].

Objective: To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer. Methods: This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery,Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher's exact test. Results: A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant (χ2 value were 156.24, 4.08, 36.56, P value were<0.01, 0.043,<0.01). Conclusion: Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

PERK signaling activation restores nucleus pulposus degeneration by activating autophagy under hypoxia environment.

OBJECTIVES: Intervertebral disc (IVD) degeneration is an important disease with no efficient biological therapy identified. Autophagy, a wildly known therapeutic target for human disease, has been demonstrated to be activated under hypoxia, with underlying mechanism remains elusive. Thus, this study aims to specify the role of autophagy in IVD degeneration, the regulating mechanism of hypoxia-inducing autophagy, and the therapeutic value of autophagy for IVD degeneration. METHODS: RNA-seq was used to screen the primary pathway affected in NP cells under hypoxia, the specific link between hypoxia and autophagy were investigated using ChIP-seq and dual luciferase reporter assay. Conditional ATG7 knockout mice (ATG7-/-) were constructed for assessing the effect of autophagy on IVD degeneration, and puncture induced mice model of IVD degeneration were used for intradiscal injection to evaluate the therapeutic value of autophagy. RESULTS: We demonstrated that hypoxia induces autophagy by transcriptional activation of autophagic gene LC3B and ATG7, which is controlled by PERK signaling. Then, we observed that inhibiting autophagy or PERK signaling leads to impaired NP cell viability and function, furthermore, using ATG7 knockout (ATG7-/-) mice, we identified the protective role of autophagy in IVD. Furthermore, we found that intradiscal injection of PERK signaling agonist, CCT020312, significantly restores the degeneration level of needle punctured mice IVD. CONCLUSION: We showed that the activation of PERK signaling upon hypoxia serves as a vital mechanism to induce autophagy and identified the therapeutic value of PERK signaling agonist for IVD degeneration treatment.

[MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance].

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.

[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

[Prenatal genetic diagnosis of the fetuses with isolated corpus callosum abnormality].

Objective: To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus. Methods: Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children's Medical Center and Qingyuan People's Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal. Results: Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses. Conclusions: Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

[Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort].

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

[Research progress of the role of iris characteristics in angle closure].

Glaucoma is a kind of optic nerve degenerative disease characterized by both depressed atrophy of optic nerve and visual field defect. In Asia, the number of patients with primary Angle closure glaucoma (PACG) is increasing year by year, posing serious impact on the life quality of patients. Angle closure is the pathogenic basis of PACG. Early identification of the risk factors for Angle closure and control on its progression are crucial to the prognosis of PACG. With the continuous in-depth study of the iris in recent years, it has been found that the changes in iris volume are also important dynamic risk factor for PACG. This paper summarizes the latest research results of both domestic and overseas, describes and summarizes the histology, biological characteristics, surface features, vascular configuration and genomics of the iris, and further analyzes the role of iris characteristics in angle closure in details, in order to provide a reference for the clinical diagnosis and research work.

Deposition of resistant bacteria and resistome through FMT in germ-free piglets.

Faecal microbiota transplantation (FMT) has received considerable attention in recent years due to its remarkable efficacy in restoring a normal gut microbiome. Here, we established the groups of post-FMT recipient piglets using germ-free piglets during early life to characterize the colonization of gut microbiota composition and the enrichment of resistance gene acquisition. By metagenomic analysis, we identified 115 bacterial phyla and 2111 bacterial genera that were acquired by the FMT recipients. We found that early-life microbial colonization and the spread of resistomes in recipient piglets were age dependent. A total of 425, 425 and 358 AR genes primarily belonging to 114, 114 and 102 different types were detected in the donors, post-FMT recipients in the FMT-3D group and post-FMT recipients in the FMT-15D group respectively. Genes that encoded tetracycline, macrolide and chloramphenicol resistance proteins were the most dominant AR genes, and the results corresponded with the exposure of antibiotic consumption at farm. Bacteroides, Escherichia, Clostridium, Parabacteroides, Treponema, Lactobacillus and Enterococcus were significantly correlated with the distribution of AR genes. More importantly, the relative abundance of AR genes was positively correlated with the levels of mobile genetic elements. Our results indicate that early-life microbial colonization can persistently shape the gut microbiota and antibiotic resistome.

[Effect of chemokines CXCL9 and CXCL10 on bone erosion in patients with rheumatoid arthritis].

OBJECTIVE: To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA. METHODS: In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People's Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman's rank correlation and Logistic regression were used for statistical analysis. RESULTS: The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P < 0.01). Spearman's correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, < 0.001, < 0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P < 0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P < 0.05). CONCLUSION: Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

[Epidemiology and the risk factors of myopia among children and youths in Yunnan province].

Objective: The purpose of the study was to describe the prevalence of myopia and to explore the associated factors of myopia among Han and Yi students aged 5-16 years in Yunnan province, China. Methods: A total of 5 971 Han and Yi students were included in the data analysis from the Yunnan eye study which was conducted from March to August, 2014. Information regarding demographic factors, socioeconomic status and lifestyle-related exposures were collected by per-designed questionnaires. The ophthalmic examinations including distance visual acuity, anterior segment examination, cycloplegic auto-refraction, and ocular motility examination were conducted. Logistic regression models were fitted to estimate the risk factors for myopia. Results: The age of 5 971 subjects was (10.68±2.24)years old, and the total prevalence of myopia and high myopia was 48.05% and 0.59%. Myopia prevalence was found to be higher in Han students compared with Yi ethnicity (50.20% vs. 47.10%,P=0.029). In multivariate analysis, the occurrence of myopia was associated with age (OR=1.28, 95%CI: 1.25-1.31), girls (OR=1.32, 95%CI: 1.18-1.48), increasing reading and writing time per day (OR=1.13, 95%CI: 1.07-1.20), having self-reported myopia among friend(s) (OR=1.15, 95%CI: 1.02-1.29), having myopic father (OR=1.38, 95%CI: 1.06-1.79), having myopic mother (OR=1.43, 95%CI: 1.12-1.83) and higher educated mother (OR=1.24, 95%CI: 1.03-1.51). Conclusions: We observed a high prevalence of myopia among Mangshi students. The presence of myopia was associated with increasing age, girls, increasing reading and writing time per day, having self-reported myopia among friend(s), having myopic father, having myopic and high educated mother.

[Long-term therapeutic effects and liver fibrosis changes with direct-antiviral therapy in HIV/HCV co-infected patients].

Objective: To investigate the long-term characteristic changes of virus, immune status, and liver fibrosis markers in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients after receiving direct-antiviral agents (DAAs). Methods: HIV/HCV co-infected patients who visited the Guangzhou Eighth People's Hospital, Guangzhou Medical University from May 2014 to December 2019 were selected as the research subjects. The changes of virological response rate, peripheral blood CD4(+)T lymphocyte level and serological markers of liver fibrosis (APRI score and FIB-4 index) were observed during 144 weeks of follow-up course after the end of DAAs treatment. Kruskal-Wallis test was used for statistical approach. Results: A total of 103 cases were included in the study. There were 87 males (87.5%), with a median age of 44 years. Sustained virological response rate at 12 weeks (SVR12) after DAAs treatment was 97.6%, and the SVR during the entire follow-up period was at least 95.9%. Compared with baseline, CD4(+)T lymphocyte count were significantly increased equally at 12 weeks (Z = -2.283, P = 0.022), 24 weeks (Z = -3.538, P < 0.001), 48 weeks (Z = -3.297, P = 0.001), 96 weeks (Z = -3.562, P < 0.001), and 144 weeks (Z = -2.842, P = 0.004). APRI score (Z = -6.394, P < 0.001) and FIB-4 index (Z = -2.528, P = 0.011) were significantly lower than baseline at week 4 of DAAs treatment, and thereafter remained at a low level, without further declination. Conclusion: HIV/HCV co-infected patients can maintain high SVR for a long time, acquire good immune reconstitution, and significantly improve liver fibrosis after DAAs treatment.

The direct effects of gonadotropin-releasing hormone on proliferation of granulosa cells and development of follicles in goose.

1. The study objectives were to determine the direct effects of gonadotropin-releasing hormone (GnRH) on the proliferation of ovarian granulosa cells (GCs) and the development of follicles in geese (Anser cygnoides) by colorimetry and ethynyl-2'-deoxyuridine (EdU) cell proliferation assays, in which primary GCs were treated with different concentrations of GnRH agonist (alarelin acetate) and an antagonist (cetrorelix acetate). Differently expressed genes (DEGs) were identified by RNA-sequencing and validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting. 2. The EdU assays showed that the proliferation of GCs was affected by the GnRH agonist and antagonist in a dose-dependent manner. The effect of treatment on cell proliferation was statistically significant at the concentrations of 10-5 mol/l alarelin and 1 mg/l cetrorelix acetate. A total of 134 DEGs (76 downregulated and 58 upregulated for alarelin treatment) and 226 DEGs (90 downregulated and 136 upregulated for cetrorelix) were identified by RNA-sequencing analysis, respectively. Enrichment analysis indicated that DEGs were enriched in the GO terms of cell-cell signalling and cell junctions. The pathways that regulate the development of follicles were identified, including the biological progress of cAMP accumulation, ovulation cycle and vasculature that are essential to follicular selection. 3. The results suggested that GnRH might directly regulate GC proliferation via autocrine or paracrine pathways related to cell junctions. In particular, it was confirmed that the mRNA and protein expression levels of the oestrogen receptor 2 (ESR2) gene, a negative transcription factor involved in follicular maturation and ovulation, were affected by GnRH agonist or antagonist in GCs. 4. In conclusion, GnRH might play an important role in follicular development by changing the expression of genes that participate in cAMP accumulation, ovulation cycle and cell junctions in ovarian GCs.

Molecular cloning of the goose GnRH gene and identification of GnRH polymorphisms associated with laying traits.

1. Egg-laying traits are important economic characteristics in goose production (Anser cygnoides). The gene GnRH, which encodes gonadotropin-releasing hormone, is a strong candidate gene for egg-laying traits in avian species. 2. In this study, a 3520 bp genomic sequence and a 279 bp mRNA sequence for GnRH, which encoded 92 amino acids, were determined. The GnRH DNA sequence contains four exons and three introns, and the DNA and deduced amino acid sequences were highly conserved across mammals (human, macaque, cow, and sheep) and avians (chicken, fulmar and quail). 3. Using a direct sequencing method, 46 single nucleotide polymorphisms (SNPs) were identified in the GnRH genomic sequence that were shared between two Sichuan White goose populations (217 and 208 individuals). Furthermore, 44 haplotypes were constructed using a sliding window approach. Association analysis between the SNPs and haplotypes and egg-laying traits showed that 10 SNPs affected the first egg weight, average egg weight, egg number at 48 weeks and egg number at 64 weeks. 4. These results lay the foundation for further studies of the function of GnRH in geese and provide a theoretical basis for marker-assisted selection of egg-laying traits in the Sichuan white goose population.

On-Demand Semiconductor Source of Entangled Photons Which Simultaneously Has High Fidelity, Efficiency, and Indistinguishability.

An outstanding goal in quantum optics and scalable photonic quantum technology is to develop a source that each time emits one and only one entangled photon pair with simultaneously high entanglement fidelity, extraction efficiency, and photon indistinguishability. By coherent two-photon excitation of a single InGaAs quantum dot coupled to a circular Bragg grating bull's-eye cavity with a broadband high Purcell factor of up to 11.3, we generate entangled photon pairs with a state fidelity of 0.90(1), pair generation rate of 0.59(1), pair extraction efficiency of 0.62(6), and photon indistinguishability of 0.90(1) simultaneously. Our work will open up many applications in high-efficiency multiphoton experiments and solid-state quantum repeaters.

Dissection of a circulating CD3+ CD20+ T cell subpopulation in patients with psoriasis.

CD3+ CD20+ T cells are a population of CD3+ T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. In this study, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3+ CD20+ T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3+ T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors. Circulating CD3+ CD20+ T cells in patients with psoriasis were enriched in CD4+ cells and displayed an activated effector phenotype, as these cells contained fewer CD45RA+ -naive and CCR7+ cells with increased activity than those of CD3+ T cells lacking CD20. In addition, compared with healthy donors, circulating CD3+ CD20+ T cells in patients with psoriasis produced more cytokines, interleukin (IL)-17A, tumour necrosis factor (TNF)-α and IL-21, but not IL-4 and IFN-γ. Furthermore, a significantly positive correlation was found between the levels of IL-17A, TNF-α and IL-21-production CD3+ CD20+ T cells with Psoriasis Area and Severity Index scores. Our findings suggest that CD3+ CD20+ T cells may play a role in the pathogenesis of psoriasis.