AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1％and PD-L1 ≥ 50％compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1＜1％com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.

Objective To investigate the effects of insulin-like growth factor 1(IGF-1)on the expression of transfor-ming growth factor β2(TGF-β2)and matrix metalloproteinase 2(MMP-2)in human retinal pigment epithelial cells(ARPE-19)and related mechanisms.Methods ARPE-19 cells were cultured for 6 h,12 h,24 h and 48 h,respectively,with dif-ferent concentrations of IGF-1 and LY294002.The cell viability was detected using the cell counting kit-8 to determine the optimal action concentration and time of IGF-1 and LY294002.The cell migration activity was detected using the cell scratch assay.The concentration of TGF-β2 in cell culture supernatant was detected using the enzyme-linked immunosorbent assay(ELISA).ARPE-19 cells were divided into the control group,IGF-1 group(80 μg·L-1 IGF-1),IGF-1+LY294002 group(80 μg·L-1 IGF-1+30 mmol·L-1 LY294002),and LY294002 group(30 mmol·L-1 LY294002)and cultured with serum-free DMEM/F12 medium,while cells in the control group received no treatment.The mRNA and protein expression levels of TGF-β2,MMP-2,phosphoinositide 3-kinase(PI3K)and protein kinase B(AKT)in the cells were measured using the re-verse transcription-polymerase chain reaction(RT-PCR)and Western blot,respectively.Results Compared with the 0μg·L-1 IGF-1 group,the cell viability in the 80 μg·L-1 IGF-1 group changed the most significantly at 24 h(P＜0.05);thus,the optimal concentration of IGF-1 was 80 μg·L-1 and the optimal culture time was 24 h.Compared with the 0 mmol·L-1 LY294002 group,the inhibition concentration in the 30 mmol·L-1 LY294002 group at 24 h was close to half;thus,the optimal concentration of LY294002 was 30 mmol·L-1 and the optimal culture time was 24 h.The cell scratch assay re-sults showed that the cell migration rate was significantly different among the 0 μg·L-1 IGF-1 group,40 μg·L-1 IGF-1 group,and 80 μg·L-1 IGF-1 group(all P＜0.05).ELISA results showed that there was a statistically significant difference in the concentration of TGF-β2 in cell supernatant among the 0 μg·L-1 IGF-1 group,40 μg·L-1 IGF-1 group,and 80 μg·L-1 IGF-1 group(all P＜0.05).RT-PCR and Western blot results showed that after 24 h culture with IGF-1 and LY294002,compared with the control group,the mRNA and protein expression levels of TGF-β2,MMP-2,PI3K and AKT in the IGF-1 group increased,while the mRNA and protein expression levels of TGF-β2,MMP-2,PI3K and AKT in the LY294002 group decreased(all P＜0.05).Compared with the IGF-1 group,the mRNA and protein expression levels of TGF-[32,MMP-2,PI3K and AKT in the IGF-1+LY294002 group decreased(all P＜0.05).Conclusion IGF-1 can promote the proliferation and migration of ARPE-19 cells.IGF-1 may up-regulate the expression of TGF-β2 and MMP-2 in ARPE-19 cells through the PI3K/AKT signaling pathway and participate in the occurrence and development of myopia.

Tuberculosis is caused by Mycobacterium tuberculosis,and the problem of its drug resistance has become increasingly prominent in recent years,attracting widespread attention globally.Currently,the situation of drug-resistant tuberculosis is grim,and effective strategies are urgently needed to deal with it.Understanding the drug resistance mechanism and treatment status of drug-resistant tuberculosis can provide an important basis for clinical prevention and treatment of drug-resistant tuberculosis.This paper reviews the progress of drug resistance mechanism and treatment of drug-resistant tuberculosis,in order to provide a reference for clinical intervention.

Objective To observe the influence of the whole process case nursing mode on the medical experience of patients undergoing oral surgery.Methods A total of 168 patients with oral surgery were chosen as research objects,and they were randomly divided into control group and obser-vation group,with 84 patients in each group.The control group was given routine nursing care,while the patients in the observation group were given whole process case nursing mode based on on the con-trol group.The medical experience and mental state scale scores in two groups were observed before and after the intervention,and the nursing satisfaction in two groups was analyzed.Results The scores of each dimension and total score of Hospital Consumer Assessment of Healthcare Providers and Systems(HCAHPS)in the observation group were higher than those in the control group(P＜0.05).After intervention,the scores of Dental Fear Scale(DFS)and Dental Anxiety Scale(DAS)in the ob-servation group were lower than those in the control group(P＜0.05).The nursing satisfaction of pa-tients in the observation team was 95.2％,which was higher than 85.7％in the control group(P＜0.05).Conclusion The whole process case nursing mode can improve the medical experience and nursing satisfaction of patients undergoing oral surgery on the basis of routine nursing,and alleviate negative emotions such as anxiety and fear.

Objective To observe the influence of the whole process case nursing mode on the medical experience of patients undergoing oral surgery.Methods A total of 168 patients with oral surgery were chosen as research objects,and they were randomly divided into control group and obser-vation group,with 84 patients in each group.The control group was given routine nursing care,while the patients in the observation group were given whole process case nursing mode based on on the con-trol group.The medical experience and mental state scale scores in two groups were observed before and after the intervention,and the nursing satisfaction in two groups was analyzed.Results The scores of each dimension and total score of Hospital Consumer Assessment of Healthcare Providers and Systems(HCAHPS)in the observation group were higher than those in the control group(P＜0.05).After intervention,the scores of Dental Fear Scale(DFS)and Dental Anxiety Scale(DAS)in the ob-servation group were lower than those in the control group(P＜0.05).The nursing satisfaction of pa-tients in the observation team was 95.2％,which was higher than 85.7％in the control group(P＜0.05).Conclusion The whole process case nursing mode can improve the medical experience and nursing satisfaction of patients undergoing oral surgery on the basis of routine nursing,and alleviate negative emotions such as anxiety and fear.

Objective:To observe the effect of a family-centered task-oriented training (TOT) program on the functional independence and life quality of children with spastic cerebral palsy.Methods:A total of 62 children with spastic cerebral palsy were randomly divided into a control group ( n=31) and a TOT group ( n=31). The children in the control group were given family rehabilitation training according to the discharge instruction manual, while the children in the TOT group received family-centered TOT. Both groups trained for 1 hour once a day, 5 days a week for 6 months. The mobility, functional independence and life quality of the two groups were evaluated with the pediatric evaluation of disability inventory (PEDI), functional independence measures for Chinese children (WeeFIM) and a pediatric quality of life inventory (PedsQL) before and after 3 and 6 months of treatment. Results:After 6 months there was significant improvement in the average mobility, WeeFIM and PedsQL scores of both groups. The average mobility, WeeFIM and PedsQL scores of the TOT group were then significantly better than those of the control group.Conclusion:Family-centered TOT training can significantly improve the functional independence and life quality of children with spastic cerebral palsy.

Objective:To investigate the value of CT features in predicting visceral pleural invasion (VPI) in clinical stage ⅠA peripheral lung adenocarcinoma under the pleura.Methods:The CT signs of 274 patients with clinical stage ⅠA peripheral lung adenocarcinoma under the pleura diagnosed in Changzheng Hospital of Naval Medical University from January 2015 to November 2021 were retrospectively analyzed. According to the ratio of 6∶4, 164 patients collected from January 2015 to August 2019 were used as the training group, and 110 patients collected from August 2019 to November 2021 were used as the validation group. The maximum diameter of the tumor (T), the maximum diameter of the consolidation part (C), and the minimum distance between the lesion and the pleura (DLP) were quantitatively measured, and the proportion of the consolidation part was calculated (C/T ratio, CTR). The CT signs of the tumor were analyzed, such as the relationship between the tumor and the pleura classification, the presence of a bridge tag sign, the location of the lesion, density type, shape, margin, boundary and so on. Variables with significant difference in the univariate analysis were entered into multivariate logistic regression analysis to explore predictors for VPI, and a binary logistic regression model was established. The predictive performance of the model was analyzed by receiver operating characteristic curve in the training and validation group.Results:There were 121 cases with VPI and 153 cases without VPI among the 274 patients with lung adenocarcinoma. There were 79 cases with VPI and 85 cases without VPI in the training group. Univariate analysis found that the maximum diameter of the consolidation part, CTR, density type, spiculation sign, vascular cluster sign, relationship of tumor and pleura and bridge tag sign between patients with VPI and those without VPI were significantly different in the training group( P<0.05). Multivariate logistic regression analysis found the relationship between tumor and pleura [taking type Ⅰ as reference, type Ⅱ (OR=6.662, 95%CI 2.364-18.571, P<0.001), type Ⅲ (OR=34.488, 95%CI 8.923-133.294, P<0.001)] and vascular cluster sign (OR=4.257, 95%CI 1.334-13.581, P=0.014) were independent risk factors for VPI in the training group. The sensitivity, specifcity, and area under curve (AUC) for the logistic model in the training group were 62.03%, 89.41% and 0.826, respectively, using the optimal cutoff value of 0.504. The validation group obtained an sensitivity, specifcity, and AUC of 92.86%, 47.06%, and 0.713, respectively, using the optimal cutoff value of 0.449. Conclusion:The relationship between the tumor and the pleura and the vascular cluster sign in the CT features can help to predict visceral pleural invasion in the clinical stage ⅠA peripheral lung adenocarcinoma under the pleura.

Objective:To screen the neutralizing epitope of enterovirus 71 (EV71) and determine the specific minimum amino acid sequence that triggers immunity for providing a theoretical basis for the development of synthetic peptide vaccines.Methods:EV71 neutralizing antibody-specific binding clones were panned and sequenced using a phage display random 12-peptide library to obtain the key sequences of neutralizing epitopes. A series of peptides containing the key sequences with N-terminal acetylation (AC) and C-terminal linking to Keyhole limpet hemocyanin (KLH) were synthesized. Serum samples were collected after immunizing mice with the modified peptides. Then the immunogenicity of the peptides and the neutralizing activity of serum samples were analyzed by Western blot, ELISA and neutralization test.Results:After three rounds of panning, cloning and sequencing, KQEKDL was identified as the key motif. The serum samples collected from the mice immunized with the modified series of peptides containing key motifs had different degrees of binding ability to EV71 and VP1 protein. The serum samples of mice immunized the synthetic peptide containing only the minimum key motif (AC-KQEKDL-KLH) had the strongest response to the other three peptides and EV71 and the highest neutralizing titer.Conclusions:The EV71 neutralizing epitope was successfully screened using the phage display random peptide library. The key motif of KQEKDL might be the specific minimum amino acid sequence that triggered the immune system. This study provides a theoretical basis for better understanding the immune response mechanism, evaluating the immunogenicity of the antigens and further research and development of polypeptide vaccines.