[Research advances on the role and mechanism of microRNA in hypertrophic scar].

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Endovascular abdominal aortic aneurysm repair with a new stent graft:early results from a multicenter study].

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.

The Burden of Colorectal Cancer Attributable to Diet Low in Fiber from 1990 to 2019: A Global, Regional and National Analysis.

OBJECTIVES: The colorectal cancer (CRC) burden is increasingly high. The aim of this study was to investigate temporal and geographical trends in CRC deaths and disability-adjusted life-years (DALYs) attributable to diet low in fiber globally from 1990 to 2019. DESIGN: Cross-sectional study. SETTING: The study based on the Global Burden of Disease Study (GBD) 2019. PARTICIPANTS: The population comprised individuals from 204 countries and territories who were diagnosed with CRC attributable to diet low in fiber from 1990 to 2019. MEASUREMENTS: Deaths, DALYs, age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) for CRC attributable to diet low in fiber were described, and estimated annual percentage change (EAPC) was further calculated to assess the burden in different regions, countries, sexes, and age groups. Additionally, we explored the association between EAPC and ASMR/ASDR (in 1990) and Human Development Index (HDI, in 2019). RESULTS: From 1990 to 2019, global ASMR and ASDR for CRC attributable to diet low in fiber decreased slightly, but the corresponding deaths and DALYs increased by 63.37% and 51.36%, respectively. Those burden varied considerably between regions and countries. The burden was higher in high, high-middle and middle SDI regions, especially in Asia and Western Europe, but when HDI > 0.7, an increasingly rapid decline in ASMR and ASDR was revealed. Unexpectedly, many less well-developed countries within the traditionally low deaths and DALYs regions of Africa, Central Latin America, and Middle East showed gradual increases in ASMR and ASDR. CONCLUSION: The global burden of CRC attributable to diet low in fiber has decreased over the last 30 years, but remains at a high level. It is essential for decision-makers to take targeted measures for improving population awareness and intake of dietary fiber.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

The SARS-CoV-2 rS1-E-PLGA nanovaccine and evaluation of its immune effect in BALB/c mice.

OBJECTIVE: Vaccination is an important method for preventing COVID-19 infection. However, certain vaccines do not meet the current needs. To improve the vaccine effect, discard ineffective antigens, and focus on high-quality antigenic clusters, S1-E bivalent antigens were designed. MATERIALS AND METHODS: Vaccine delivery is performed using poly (lactic-co-glycolic acid) (PLGA). Here, the recombinant S1-E (rS1-E) was covered on PLGA and injected intramuscularly into mice. In total, 48 BALB/c mice were randomly divided into six groups with 8 mice in each group. The mice received intramuscular injections. Prior to vaccination, the hydrophobicity of the rS1-E and the antigenic site of the E protein were both analysed. The morphology, zeta potential, and particle size distribution of rS1-E-PLGA were examined. Anti-S1 and anti-E antibodies were detected in mouse serum by ELISA. Neutralising an-tibodies were detected by co-incubating the pseudovirus with the obtained serum. IL-2 and TNF-α levels were also measured. RESULTS: The designed recombinant S1-E protein was successfully coated on PLGA nanoparticles. rS1-E-PLGA nanovaccine has suitable size, shape, good stability, sustained release and other characteristics. Importantly, mice were stimulated with rS1-E-PLGA nanovaccines to produce high-titre antibodies and a good cellular immune response. CONCLUSIONS: Our results indicate that rS1-E-PLGA nanovaccine may provide a good protective effect, and the vaccine should be further investigated in human clinical trials for use in vaccination or as a booster.

[The incidence and mortality of endometrial cancer in China, 2015].

Objective: To estimate endometrial cancer (EC) incidence and mortality in China in 2015. Methods: Qualified cancer registry data collected in 2011-2015 were pooled for analysis, from which EC cases and deaths were extracted. EC cases were classified into endometrioid, nonendometrioid and other & unspecified according to their histologic types. Incidence and mortality rates stratified by region and age group were calculated. Population data of 2015 was used to estimate cancer cases and deaths in China. Segi's population was used for the calculation of age-standardized rates by world standard population (ASW). Results: Data from 158, 176, 239, 235, 231 qualified cancer registries of 2011 to 2015 were pooled together. These registries covered about 488 million population, including about 255 million population in urban area and 233 million population in rural area. In 2015, a total of 53 600 EC cases were estimated, with a crude incidence rate of 7.74/100 000 and an ASW of 5.13/100 000. Incidence rates were higher in urban areas (9.15/100 000) than in rural areas (6.20/100 000). A total of 10 700 deaths were estimated, with a crude mortality rate of 1.60/100 000 and an ASW of 0.98/100 000. Mortality rate was higher in urban areas (1.78/100 000) than in rural areas (1.40/100 000). Among reported EC cases during 2011-2015, 70.92% (23 641 cases) were endometrioid, 5.13% (1 709 cases) were nonendometrioid and 23.95% (7 982 cases) were other & unspecified. The mean age at onset of all EC cases was 55.9±10.6. The mean age at onset of endometrioid cases (55.7±10.0) was younger than that of nonendometrioid cases (57.7±10.8) (P<0.001). The mean age at onset of all histologic types in urban areas was higher than that in rural areas (P<0.001). The mean age at death for EC deaths was 63.9±12.5. The mean age at death in urban areas (65.3±12.5) was higher than that in rural areas (61.4±12.2) (P<0.001). Conclusion: EC disease burden differs between urban and rural areas. Targeted cancer prevention and control strategies should be made for each region.

[Clinical characteristics of 114 patients with iridocorneal endothelial syndrome].

Objective: To investigate the clinical features in patients with iridocorneal endothelial (ICE) syndrome. Methods: A retrospective case series study. Data of clinical manifestations of patients with ICE syndrome including clinical subtypes, presenting visual acuity, clinical features and secondary glaucoma were collected from January 2014 to May 2020 in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University. The Wald's Chi-square test of generalized estimating equations was performed to analyze the differences in three clinical subtypes. Results: A total of 127 eyes of 114 subjects (64 females and 50 males) were included. Mean±SD age at presentation was (49±13) years. There were 53 patients (46.5%) with Chandler's syndrome (CS), 36 patients (31.6%) with progressive iris atrophy (PIA), 24 patients (21.0%) with Cogan-Reese syndrome (CRS) and one patient (0.9%) with an undetermined subtype. And 101 patients (88.6%) had uniocular ICE syndrome. Approximately 81.7% (49/60), 56.1% (23/41) and 41.7% (10/24) of eyes presented visual acuity <0.3 in patients with CS, PIA and CRS, respectively. Corneal edema was most common in CS (52.5%, 32/61), followed by PIA (29.3%, 12/41) and CRS (20.8%, 5/24). Corectopia was found in 95.8% (23/24) of eyes with CRS, 95.1% (39/41) of eyes with PIA and 78.7% (48/61) of eyes with CS. Polycoria was observed in 29.3% (12/41) of eyes with PIA, 3.3% (2/61) of eyes with CS and 8.3% (2/24) of eyes with CRS. Ectropion uvea was most common in CRS (54.2%, 13/24), followed by 16.4% (10/61) in CS and 12.2% (5/41) in PIA. Glaucoma was found in 94 eyes (74.0%, 94/127). Among them, 60.7% (37/61) of CS, 80.5% (33/41) of PIA and 95.8% (23/24) of CRS had secondary glaucoma. The difference of presenting visual acuity, corneal edema, corectopia, polycoria, ectropion uveae and secondary glaucoma in three clinical subtypes all had statistical significance (Wald χ2=13.87, 10.77, 965.78, 11.45, 15.00, 222.04; all P<0.05). And 86.2% of eyes (81/94) had glaucoma surgeries and 41 eyes (43.6%, 41/94) had the intraocular pressure well controlled with various interventions. Conclusions: ICE syndrome is mostly uniocular and more common in middle-aged patients. CS is the most common clinical subtype with poor presenting visual acuity. About 3/4 of eyes have secondary glaucoma, and the majority of them require surgical interventions, but prognoses are discouraging.

[Identification of serum peptide biomarker for ovarian cancer diagnosis by Clin-TOF-II-MS combined with magnetic beads technology].

Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (CLL) is associated with immunosuppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination. We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 286 patients underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine (n = 267) compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine (n = 55), compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine. This work supports the need for optimisation of vaccination strategy in patients with CLL including the potential utility of booster vaccines.

[Analysis of PARP inhibitors induced anemia in advanced and relapsed epithelial ovarian cancer].

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

The split-off terahertz radiating dipoles on thermally reduced α-V2O5 (001) surface.

The trapped electron states on a pliable lattice have different localization and physical chemistry characteristics. Here, terahertz time-domain measurements suggest that the formation of vanadyl oxygen defect, in the presence of the surface potential traps and mobile charge carriers, leads to a transient charge distribution that forms terahertz radiating dipoles in V2O5. The emergence of radiating dipoles is evidenced by terahertz responses with a two-valley feature of the thermally reduced α-V2O5 (001) thin films in the temperature range of 300-700 K. The two photoconductance valleys on a several millielectron volts interval are related to two emergent split-off traps, which originate from the VO6 octahedra distortion upon the vanadyl oxygen desorption on the surface. The pliable surface lattices plays a decisive role. So long as the α-V2O5 (001) thin films are covered by a 30 nm-thick Al2O3 capping layer, the distinct two-valley feature disappears completely in the full temperature range. The terahertz radiating dipoles with a fine energy structure is potentially a new measure for charge dynamics on the α-V2O5 (001) surface.

CircRNA_002178 promotes the proliferation and migration of oral squamous cell carcinoma cells by activating the Akt/mTOR pathway.

OBJECTIVE: We aimed to investigate the biological effects of circRNA_002178 in oral squamous cell carcinoma (OSCC) tissues and to analyze its potential mechanism. PATIENTS AND METHODS: CircRNA_002178 expression in 50 pairs of OSCC tissues and adjacent ones was studied by quantitative polymerase chain reaction (qPCR) analysis, and the correlations of circRNA_002178 with clinicopathological indicators, as wells as prognosis of OSCC patients were analyzed. qPCR was used to verify circRNA_002178 expression in OSCC cell lines. Subsequently, circRNA_002178 knockdown models were constructed using lentivirus in OSCC cell lines, and the impacts of circRNA_002178 on the function of OSCC cells were assessed by cell counting kit-8 (CCK-8) test, plate cloning experiment, transwell assay and nude mouse tumor formation experiments. Finally, rescue experiments in vitro were used to explore the potential mechanism of circRNA_002178 activating Akt/mTOR pathway. RESULTS: Our data showed that circRNA_002178 expression in OSCC tissue specimens was remarkably higher than that in adjacent ones. In comparison to patients in low circRNA_002178 expression group, patients in high expression group showed higher incidences of advanced pathological stage and distant metastasis, and a lower overall survival rate. Cell functional experiments revealed that knockdown of circRNA_002178 markedly attenuated the proliferation and migration ability of OSCC cells compared to the sh-NC group, and the consistent results were observed in the nude mouse experiment. In addition, Western blot suggested that the expression of key proteins in Akt/mTOR signaling pathway was remarkably reduced after downregulation of circRNA_002178 in OSCC cells. Meanwhile, Akt activator SC79 reversed the inhibitory effect of circRNA_002178 on the metastasis and proliferation of OSCC cells. CONCLUSIONS: CircRNA_002178, over-expressed in OSCC tissues and cell lines, may promote the malignant progression of OSCC through activating the Akt/mTOR signaling pathway.

Maintenance treatment in advanced HER2-negative gastric cancer.

Survival for patients with advanced gastric cancer (GC) remains poor. Systemic chemotherapy which has reached a plateau stays the standard first-line (1L) treatment for advanced human epidermal growth-factor receptor 2 (HER2)-negative GC. To maximize the benefit of 1L treatment, the concept of maintenance treatment is constantly being explored. In advanced HER2-negative GC, current clinical guidelines do not recommend a standard maintenance therapy strategy. In addition to the monotherapy maintenance with fluorouracil after 4-6 cycles of 1L chemotherapy, some agents that are active against novel targets have been evaluated in clinical trials for maintenance treatment. Whereas most of these trials do not reach their primary endpoints, they open new horizons for the 1L treatment of advanced HER2-negative GC. Therefore, we reviewed the clinical trials in the field of maintenance treatment in advanced HER2-negative GC and discussed some of the problems in clinical trials.

Intravitreal conbercept for branch retinal vein occlusion induced macular edema: one initial injection versus three monthly injections.

BACKGROUND: To compare the efficacy of one initial intravitreal injection of conbercept (IVC) versus three monthly IVCs in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). Both options were followed by a pro re nata (PRN) retreatment regimen. METHODS: This study retrospectively investigated and followed 60 patients with acute ME secondary to BRVO for over a year. 30 subjects received one initial injection (1 + PRN group); while, 30 received three monthly injections (3 + PRN group). The functional and anatomic outcomes were assessed during each follow-up. RESULTS: The general characteristics of the 60 subjects were as follows: mean [SD] age, 57.43 [13.06] years; 33 [55%] female; 36 [60%] non-ischemic form. Both groups showed a stable gain in visual acuity (VA) with similar logMAR (mean ± SD) (1 + PRN group 0.308 ± 0.399, 3 + PRN group 0.34 ± 0.352) during the first 12 months. Additionally, both groups exhibited a significant reduction in central foveal thickness (CFT) with no statistically significant difference between them (1 + PRN group 222.1 µm ± 197.1 µm, 3 + PRN group 228.4 µm ± 200.2 µm). Both treatment groups had similar improvements in logMAR and anatomic outcomes over time. The stratified analysis showed that patients with the non-ischemic form and those with the ischemic form had similar improvements in VA (0.346 ± 0.366 VS 0.29 ± 0.39, P = 0.575) during the 12 months follow-ups. The number of injections was lower in the 1 + PRN group (4.0 ± 1.6) than in the 3 + PRN group (4.7 ± 1.3) (P = 0.068). No adverse effects or unexpected safety issues were reported in either group. CONCLUSIONS: Conbercept yielded significant improvements in VA and CFT among patients with BRVO induced ME, independent of their retinal ischemia status. The results showed that the 3 + PRN regimen do not lead to better functional outcomes or lower treatment needs in clinical practice as compared to the 1 + PRN regimen.

[Programmed cell death protein 1 and its ligands regulate immune balance in allergic rhinitis].

Objective: To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR). Methods: Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1(+)CD4(+)T cells, PD-L1(+) myeloid dendritic cells (mDCs), PD-L2(+)mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P<0.05 was considered statistically significant. Results: The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1(+)CD4(+)T cells, PD-L1(+)mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P<0.05). There was no significant difference in the ratio of PD-L2(+)mDCs between the two groups. Correlation analysis found that the proportion of PD-1(+)CD4(+) T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration (r value was 0.501, 0.541, 0.608, respectively, all P<0.05). The proportion of PD-L1(+)mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration (r value was 0.604, 0.563, respectively, all P<0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1(+)mDCs and PD-1(+)CD4(+)T cells (r value was 0.538, 0.623, respectively, all P<0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P<0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration (r values was 0.32, 0.45, respectively, all P<0.05). Conclusions: PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

[Advances of studies on the occurrence of the upper respiratory disease correlative with immunity and tobacco].

SummaryTobacco smoke exposure has obvious and complex effects on the immune system of the human upper respiratory tract, including pro-inflammatory and anti-immune effects. Exposure to tobacco smoke is closely related to the occurrence and development of allergic rhinitis, the common rhinitis and sinusitis. The innate immune system is influenced by tobacco smoking through its effects on the respiratory mucosa and its adjuncts, natural killer cells, dendritic cells, neutrophils and innate immune receptors. Cigarette smoke can also affect the humoral immunity and cellular immunity, altering the acquired immune condition of the upper respiratory tract. Tobacco smoke exposure promotes the occurrence and development of the upper respiratory tract infectious diseases and allergic diseases by changing the composition of microflora in the upper respiratory tract.

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases.

BACKGROUND: Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta-analysis was undertaken to evaluate its prognostic value. METHODS: References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease-free survival after hepatic resection between patients with CRLM originating from right- or left-sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. RESULTS: The final analysis included 21 953 patients from 45 study cohorts. Compared with left-sided primary tumour location, right-sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease-free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right-sided primary tumour location on overall survival was more prominent in the non-Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). CONCLUSION: This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.

ANTECEDENTES: La ubicación del tumor primario (primary tumor location, PTL) ha surgido como un factor pronóstico importante en los cánceres colorrectales (colorectal cancers, CRCs) localizados y metastásicos. Sin embargo, todavía se discute su relevancia como factor pronóstico tras la resección de metástasis hepáticas de cáncer colorrectal (colorectal liver metastases, CRLM). Se realizó una revisión sistemática y un metaanálisis para determinar su valor pronóstico. MÉTODOS: En PubMed, EMBASE, Web of Science y la Biblioteca Cochrane se identificaron los trabajos que compararon la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease-free survival, DFS) tras la resección hepática de CRLM cuyo CRCs estuviese situado en el lado derecho o izquierdo. Los datos se expresaron en forma del cociente de riesgos instantáneos (hazard ratio, HR) e intervalos de confianza del 95% (i.c. del 95%) de acuerdo con un modelo de efectos aleatorios. Se efectuaron análisis de metarregresión y de subgrupos para evaluar el efecto de los factors de confusión existentes en las estimaciones de HR, ajustando por los mismos. RESULTADOS: El análisis final incluyó 21.953 pacientes de cohortes de 45 estudios. La PTL en el lado derecho en comparación con el lado izquierdo se asoció con una peor supervivencia global (HR 1,39; i.c. del 95% 1,28-1,51; P < 0,001; intervalo de predicción 1,00-1,93) y una tendencia a un impacto negativo en la DFS (HR 1,18; i.c. del 95% 1,06-1,32; P = 0,004; intervalo de predicción 0,79-1,75). El análisis de subgrupos mostró que el efecto negativo de la PTL del lado derecho en la OS fue más prominente en la población no asiática (HR 1,47; i.c. del 95% 1,33-1,62) que en la asiática (HR 1,18; i.c. del 95% 1,05-1,32; Pinteracción < 0,01). CONCLUSIÓN: Este estudio demostró que la PTL tiene un papel pronóstico tras la hepatectomía de las CRLM, especialmente respecto a la OS. La adición de la PTL proporcionaría una optimización importante en los modelos actuales de predicción pronóstica de CRLM.