Lipopolysaccharide (LPS) was used to induce mouse mononuclear macrophages (RAW 264.7 cells) to establish the inflammation model for investigating the effect and mechanism of Mailuoning oral liquid on arteriosclerosis occlusion (ASO) in vitro. RAW264.7 cells viability was measured by MTT assay. NO concentration was determined by Griess. mRNA levels and protein expressions of NFAT5/NLRP3 signaling pathway were detected by Q-PCR and Western blot. The relationship between NFAT5 and NLRP3 was explored by cellular transfection of NFAT5-siRNA combined with Western blot. Nuclear translocation of NFAT5 was detected by immunofluorescence. The results showed that Mailuoning oral liquid decreased the NO release induced by LPS in RAW264.7 cells. The mRNA levels of NFAT5, NLRP3, caspase1, IL-18 and MMP9, the protein expressions of NFAT5, NLRP3, cleaved-caspase1 (p20) and the phosphorylation of NF-κB-P65 were decreased after administration of Mailuoning oral liquid. NFAT5-siRNA significantly reversed the increase in protein expressions of NLRP3 induced by LPS in RAW264.7 cells. Both Mailuoning oral liquid and KRN2 (NFAT5 inhibitor) could inhibit the expressions and nuclear translocation of NFAT5. In conclusion, Mailuoning oral liquid exert significant anti-inflammatory effects in vitro by inhibiting the NFAT5/NLRP3 signaling pathway, and NFAT5 might be involved in regulating the expressions of NLRP3.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

OBJECTIVE To evaluate the efficacy and safety of four cyclin-dependent kinase 4/6 （CDK4/6） inhibitors （dalpicilib， abemacilib， ribocilib， palbocilib） combined with endocrine drugs in the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2－） breast cancer. METHODS Computer searches were conducted on PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang data and VIP to collect randomized controlled trials （RCTs） about CDK4/6 inhibitors combined with endocrine drugs （trial group） versus endocrine drugs alone or combined with placebo （control group）. The search period was from the establishment of the database to April 2023. After literature screening， data extraction and quality evaluation， a meta-analysis was conducted by using RevMan 5.4.1 software. RESULTS A total of 22 articles were included， involving 15 RCTs with a total of 18 574 patients. The meta-analysis results showed that the progression free survival [HR＝0.77， 95%CI （0.74， 0.79）， P＜0.000 1]， overall survival [HR＝0.91， 95%CI （0.87， 0.94）， P＜0.000 01]， objective response rate [OR＝1.71， 95%CI （1.51， 1.93）， P＜0.000 01] and clinical benefit rate [OR＝1.73， 95%CI （1.52， 1.95）， P＜0.000 01] of the trial group were significantly better than control group. The incidence of adverse drug reactions≥3 levels [OR＝10.28，95%CI （6.97，15.17），P＜0.000 01]， neutropenia [OR＝65.09， 95%CI （36.43， 116.31）， P＜0.000 01]， leukopenia [OR＝22.90， 95%CI （15.40， 34.04）， P＜0.000 01]， anemia [OR＝5.71， 95%CI （4.51， 7.22）， P＜0.000 01]， diarrhea [OR＝ 3.00， 95%CI （1.19， 7.51）， P＜0.05] and nausea [OR＝1.99， 95%CI （1.52， 2.60）， P＜0.000 01] in the trial group was significantly higher than control group. CONCLUSIONS The combination of CDK4/6 inhibitors and endocrine drugs has a significant effect on HR+/HER2－ breast cancer， with a high incidence of adverse reactions， especially hematotoxicity.

OBJECTIVE To evaluate the effectiveness， safety and economics of Aidi injection combined with first-line chemotherapy for non-small cell lung cancer （NSCLC）， and to provide evidence-based reference for clinical drug use and decision. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang databases， VIP and Health Technology Assessment （HTA） related websites， HTA reports， systematic evaluation/meta-analysis and economic evaluations about Aidi injection combined with first-line chemotherapy for NSCLC were collected from the inception to Aug. 2022. After data extraction and quality evaluation， descriptive analysis was performed for the results of included studies. RESULTS A total of 16 pieces of literature were included， involving 1 piece of systematic review， 13 pieces of meta-analysis， 2 pieces of pharmacoeconomic studies. Compared with first-line chemotherapy， Aidi injection combined with first-line chemotherapy could improve response rate and disease control rate， prolonged survival time， improved survival quality， reduced the incidence of nausea and vomiting， leukocytopenia and thrombocytopenia， and improved immune function， but had controversial effects on liver and kidney function. With the payment threshold set by 3 times the national per capita GDP in 2019， Aidi injection combined with first-line chemotherapy had a more economical probability. CONCLUSIONS Aidi injection combined with first-line chemotherapy for NSCLC has good efficacy and safety， and has certain economic benefits. However， given the limited pharmacoeconomic studies included， the economic conclusions obtained need to be carefully interpreted.

Objective:To evaluate the distribution characteristics of choroidal vascularity index (CVI) in macula among normal children using swept-source optical coherence tomography (SS-OCT), and to investigate the influencing factors.Methods:A cross-sectional study was conducted.Sixty-three children aged 6 to 12 years were enrolled in The First Affiliated Hospital of Zhengzhou University from May 2021 to November 2021.Spherical equivalent refraction, axial length (AL) and other ocular biological parameters were measured.Macula-centered CVI and choroidal thickness (ChT) were measured by SS-OCT angiography.According to the ETDRS partition, the obtained image was divided into macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter) zones.Data from the right eye were selected for statistical analysis.CVI in the three rings and four zones (superior, temporal, inferior and nasal zones) of the inner and outer rings were compared.Univariate and multiple linear regression analyses were used to analyze the correlation between CVI and sex, AL, anterior chamber depth (ACD), ChT and pupil diameter.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-0399-003). Written informed consent was obtained from each guardian.Results:The average CVI in the macular central fovea, inner ring and outer ring were 0.35±0.12, 0.32±0.10 and 0.27±0.08, respectively, with a significant difference ( F=10.96, P<0.001), and significant differences in CVI were found in pairwise comparisons of the three ring zones (all at P<0.05). Significant differences in CVI were found among superior, temporal, inferior and nasal zones in inner and outer rings ( Fring=11.60, P=0.001; Fzone=12.02, P<0.05). The CVI was smaller in superior and nasal zones in inner ring than in temporal zone, greater in superior, temporal and inferior zones in outer ring than in nasal zone, smaller in superior zone of outer ring than that of the inner ring, and the differences were statistically significant (all at P<0.001). The single factor linear regression analysis showed that ChT in the fovea, inner ring and outer ring were the influencing factors of CVI in the three ring zones (all at β=0.001, P<0.001). Pupil diameter ( β=0.034, P=0.038; β=0.040, P=0.003; β=0.024, P=0.011) and ACD ( β=0.097, P=0.034; β=0.097, P=0.013; β=0.061, P=0.032) were the influencing factors of CVI in fovea, inner ring and outer ring.After multiple linear regression analysis, the regression equations were established as follows: CVI in the macular fovea=0.001×ChT in the macular fovea + 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.301 ( R2=0.514, F=6.875, P<0.001); CVI in the inner ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring+ 0.088×AL-0.307 ( R2=0.603, F=9.870, P<0.001); CVI in the outer ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.135 ( R2=0.601, F=9.781, P<0.001). Conclusions:In children aged 6-12 years old, the CVI is higher in the macular central fovea than in inner and outer rings, and the CVI in nasal zone is the smallest in both inner and outer rings.The thicker the ChT, the higher the CVI in all zones in the macular area; the deeper the anterior chamber, the higher the CVI in the inner ring.

Objective:To observe the safety and efficacy of 0.01% atropine eye drops in the prevention of myopia onset in schoolchildren.Methods:A randomized double-blind controlled study was conducted.Sixty Chinese Han children (60 eyes) with binocular spherical equivalent (SE) between + 0.50 D and -0.75 D (pre-myopia) by cycloplegic autorefraction treated in The First Affiliated Hospital of Zhengzhou University were enrolled from July to October 2020.Aged 6-12 years old, the children were divided into 0.01% atropine group and control group according to a random number table, with 30 cases (30 eyes) in each group.The children were given one drop of 0.01% atropine or placebo eye drops in both eyes once a night.The SE, axial length (AL), accommodative amplitude and pupil diameter were compared before and after 3-month, 6-month of treatment between the two groups.Discomforts were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2020-KY-286). Written informed consent was obtained from guardian of each subject.Results:After treatment, 26 and 25 subjects completed the 6-month follow-up in 0.01% atropine group and control group, respectively, among which 3 subjects in 0.01% atropine group accounting for 11.5% and 9 in control group accounting for 36.0% developed myopia, showing a statistically significant difference ( χ2=4.238, P=0.040). There were significant differences in the overall comparison of SE and AL at different time points between before and after treatment ( Ftime=10.981, 81.854; both at P<0.001). At 3 and 6 months after treatment, there were significant increases in the SE and AL of control group and AL of 0.01% atropine group compared with respective baseline values (all at P<0.05). There was no significant difference in SE at 3 and 6 months after treatment compared with baseline SE in 0.01% atropine group (both at P>0.05). At 6 months after treatment, the change in SE in 0.01% atropine group was (-0.15±0.26)D, which was significantly less than (-0.34±0.35)D in control group, and the change in AL in 0.01% atropine group was (0.17±0.11)mm, Which was significantly shorter than (0.28±0.14)mm in control group, with significant differences between them ( t=2.207, P=0.032; t=3.127, P=0.003). There were significant differences in pupil diameter at different time points between before and after treatment ( Ftime=2.263, P=0.032). At 3 and 6 months after treatment, the pupil diameter was increased in comparison with baseline in 0.01% atropine group (both at P<0.05). There were significant differences in accommodative amplitude at different time points between before and after treatment in the two groups ( Fgroup=0.882, P=0.042; Ftime=0.337, P=0.033). The accommodative amplitude at 3 and 6 months after treatment were decreased in comparison with baseline in 0.01% atropine group and control group at corresponding time points (all at P<0.05). Within a month after treatment, photophobia in bright sunlight occurred in 5 cases in 0.01% atropine group, accounting for 16.7%(5/30), and 2 cases in control group, accounting for 6.7%(2/30), showing no significant difference ( χ2=0.647, P=0.421). No near-vision blur and other uncomfortable symptoms was found in the two groups. Conclusions:After 6-month application of 0.01% atropine eye drops, the prevalence of myopia in pre-myopia schoolchildren decreases and the changing rate of SE and AL slows down.The accommodative amplitude is slightly reduced and pupil diameter is slightly increased, with no obvious effects on study and life.

Objective:To analyze the characteristics of sleep disordered breathing (SDB) in children with allergic rhinitis (AR), and improve the diagnosis and treatment at AR combined with obstructive sleep apnea (OSA).Methods:The clinical data of 120 patients with AR and OSA (AR and OSA group) admitted to the respiratory department at Shenzhen Children′s Hospital from May 2019 to December 2020 were retrospectively analyzed.A total of 120 children diagnosed with OSA and excluded AR during the same period were selected as control group.The SDB day and night symptoms, sleep structure characteristics and sleep breathing events were compared between two groups.Results:The average course of disease in children with AR and OSA was significantly longer than that in control group ( P=0.030). The main manifestations of children in AR and OSA group were mouth breathing (100.0%), snoring (99.2%), nasal obstruction (88.5%), and restless sleep (68.0%). There was no significant difference in sleep structure between two groups ( P>0.05), but the sleep efficiency of AR and OSA group was significantly lower than that of control group ( P=0.028). The respiratory events apnea hypopnea index, obstructive apnea index, obstructive apnea hypopnea index, hypopnea index and oxygen desaturation index of each sleep period in AR and OSA group were significantly higher than those in control group ( P<0.05). Among the children in AR and OSA group, moderate and severe OSA were the main manifestations, and the difference between two groups was statistically significant ( P<0.001). Conclusion:The combination of AR delayed the course of OSA in children.The main characteristics of sleep disordered breathing in children with AR are mouth opening, restless sleep, snoring and nasal obstruction.The sleep efficiency is decreased.Obstructive hypopnea and apnea are the most common respiratory events, and oxygen deficiency often occurs in rapid eye movement phase.Children with AR are more likely to have moderate or severe obstructive sleep apnea.

Objective:To analyze the relationship between physical appearance perfectionism, negative body self, fear of negative evaluation and social appearance anxiety in female patients with psoriasis.Methods:A total of 251 female patients with psoriasis in Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong University from June 2019 to June 2020 were selected as the subjects. Physical Appearance Perfectionism Scale (PPAS), Social Appearance Anxiety Scale (SAAS), Brief Fear of Negative Evaluation Scale (BFNES) and Negetive Physical Self Scale (Npss) were used in the survey. The correlation of negative body self and negative evaluation fear between the appearance perfectionism and social appearance anxiety of female psoriasis patients was analyzed.Results:The score of physical appearance perfectionism was 49.42±5.32, the score of social appearance anxiety was 58.72±6.24, the score of fear of negative evaluation was 30.59±7.21 and the score of negative physical self was 29.21±6.24. Pearson correlation analysis showed that there was a significant positive correlation among physical appearance perfectionism, social appearance anxiety, fear of negative evaluation and negative physical self ( r value was 0.402-0.488, P<0.01). The mediating effect of negative physical self between physical appearance perfectionism and social appearance anxiety was 0.164 (95% CI 0.082-0.227), the mediating effect of negative body self between physical appearance perfectionism and social appearance anxiety was 0.152 (95% CI 0.079-0.214) and the chain mediating effect of fear of negative evaluation and negative physical self was 0.067 (95% CI 0.025-0.108). Conclusions:Female patients with psoriasis have a high level of physical appearance perfectionism, which can directly affect their social anxiety, while fear of negative evaluation and negative physical self indirectly affect the correlation between appearance perfectionism and social appearance anxiety. Psychological intervention measures should be taken to reduce their psychological burden on their own appearance defects and carry out social anxiety and fear.

Objective: The study presents a new method to prefabricate the nasoalveolar molding appliances for preoperative cleft lip and palate by using three-dimensional technology. Methods: A long term retrospective study of 40 cases of infants with unilateral cleft lip and palate who underwent the preoperative 3D models of alveolar bone acquisition, computer aided design for the rapid prototyping process, gypsum powder printing maxillary three-dimensional entity model and install the appliance for 3-4 months (or alveolar cleft<2 mm). Simultaneously, primary rhinoplasty can be done during cleft lip repair. All patients had clinic visits three times each month. Results: Deformities of infants who underwent this treatment, were significantly improved. The alveolar cleft was significantly reduced (P<0.01), while bilateral alveolar tissue volume was significantly increased (P<0.01). Alveolar bone morphology was more symmetrical than before. Conclusions The digital design and manufacture system of appliances for preoperative cleft lip and palate can be successfully applied to the preoperative orthodontic treatment. The sequence treatment of cleft lip and palate becomes better improved. It can shorten the time duration and the numbers of clinic visit on the basis of ensuring the accuracy of preoperative orthodontic effect.