Objective:To study the relationship between the dynamic changes of angiopoietin-2 (Ang-2) and surfactant protein D (SP-D) in pediatric acute respiratory distress syndrome (pARDS) and the severity and prognosis of the disease.Methods:Using nested case-control study method, 80 children with pneumonia complicated with pARDS admitted to PICU at Fujian Maternal and Child Health Hospital from June 2018 to May 2021 were selected as pARDS group, and 19 healthy children with corresponding age were selected as control group.According to the oxygenation, the children in pARDS group were divided into three subgroups: mild group (23 cases), moderate group (32 cases) and severe group (25 cases). According to the prognosis at discharge, the children in pARDS group were divided into survival group (67 cases) and death group (13 cases). Ang-2 and SP-D were detected by enzyme-linked immunosorbent assay.The levels of Ang-2 and SP-D in children with pARDS of different severity on the first day were compared; The changes of Ang-2 and SP-D levels on the 1st, 3rd and 8th day of children in survival group and death group were compared, and the receiver operating characteristic (ROC) curve was plotted to compare the predictive value of Ang-2 and SP-D for pARDS prognosis.Results:(1) The levels of Ang-2 and SP-D on the first day in pARDS group were significantly higher than those in control group( P<0.001). (2) The levels of Ang-2 and SP-D on the first day in children with pARDS of different severity levels were significantly different ( P<0.001), and the levels of Ang-2 and SP-D increased gradually with the increase of disease severity.(3) The levels of Ang-2 and SP-D in death group were significantly higher than those in survival group on the 1st, 3rd and 8th day ( P<0.05). (4) Prognostic efficacy of Ang-2 and SP-D levels in pARDS group at different time points: when the areas under the ROC curve predicted by Ang-2 on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.808, 0.981 and 0.989, respectively; the optimal cut-off values were 6 000 pg/mL, 6 971 pg/mL and 4 171 pg/mL, respectively; the sensitivity was 84.6%, 92.3% and 92.3%, respectively; and the specificity was 76.1%, 97.0% and 98.5%, respectively.The areas under the ROC curve predicted by SP-D on the 1st, 3rd and 8th day for inpatient mortality in children with pARDS were 0.689, 0.993 and 0.983, respectively; the optimal cut-off values were 13544 pg/mL, 16003 pg/mL and 12294 pg/mL, respectively; the sensitivity was 84.6%, 100.0% and 100.0%, respectively; and the specificity was 46.3%, 98.5% and 97.0%, respectively. Conclusion:Serum Ang-2 and SP-D levels in children with pARDS increase with the aggravation of the disease.The dynamic changes of Ang-2 and SP-D in children with pARDS with different prognosis are different during the course of disease, and monitoring serum Ang-2 and SP-D during the course of disease has a certain predictive value for clinical outcome.

AIM: To compare the efficacy of Jensen and augmented Hummelsheim procedures in the treatment of complete paralytic esotropia.METHOD: A total of 35 patients(44 eyes)who were diagnosed with complete paralytic esotropia from October 2016 to October 2020 were retrospectively analyzed, of which 15 cases(21 eyes)underwent Jensen procedure combined with recession of antagonist muscle(Jensen procedure group), and 20 cases(23 eyes)received augmented Hummelsheim procedure combined with recession of antagonist muscle(Hummelsheim procedure group). The operation time, preoperative and postoperative esotropia deviation, degree of abduction paralysis, recession of medial rectus muscle and cure rate were observed.RESULTS: Clinical data and operation time of the patients in two groups were not statistically significant(P >0.05). During the last follow-up, the esotropia deviation of Jensen procedure group decreased from 102.33±41.70PD to 3.93±4.82PD(P<0.001), and it decreased from 94.75±33.03PD to 2.85±5.96PD in Hummelsheim procedure group(P<0.001), while the degree of abduction paralysis were significantly improved from -4.81±0.40 to -1.57±0.51 in the Jensen procedure group(P<0.001)and from -4.91±0.29 to -1.22±0.42 in Hummelsheim procedure group(P<0.001). Besides, there was no statistical difference in postoperative esotropia deviation between the two groups(P>0.05), but the degree of postoperative abduction paralysis in the Hummelsheim procedure group was significantly better than that of Jensen procedure group(P<0.05). The recession of medial rectus muscle of the two groups were 7.16±2.07 and 6.37±2.34 mm, respectively(P>0.05). During the last follow-up, in the Jensen procedure group, 2 patients were undercorrection(+10PD and +12PD respectively)and 13 cases(87%)were cured. In the Hummelsheim procedure group, 1 patient was undercorrection(+25PD)and 19 patients were cured(95%), and there was no statistical significance in cure rates of the two groups(P=0.565).CONCLUSIONS: Both Jensen procedure and augmented Hummelsheim procedure can effectively treat complete paralytic esotropia, and the latter is more effective in improving the abduction paralysis.

Humans ; Female ; Coronary Artery Disease/complications* ; Hyperlipoproteinemia Type II/complications* ; Aortic Valve Stenosis/etiology* ; Treatment Outcome

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

AIM: To analyze the clinical characteristics and treatment of patients with acute acquired concomitant esotropia(AACE)in different refractive status.METHODS: A retrospective analysis was conducted on 110 patients with non-type I AACE treated from January 2020 to January 2022. The non-myopic group(30 cases, spherical equivalent>-0.5D)and the myopic group(80 cases, spherical equivalent≤-0.5D)were divided according to the refractive status. The degree of deviation, accommodative convergence and accommodation ratio(AC/A), visual function, and surgical methods were observed. RESULTS: The non-myopic group had no difference in the degree of near deviation [(47.13±23.54)△] and the degree of distant deviation [(48.90±22.59)△](P>0.05); near deviation [(40.49±26.09)△] of myopic group was less than distant deviation [(50.09±25.41)△](P<0.001); and there was no difference in the same distance between the two groups(P>0.05). AC/A in the non-myopic group(5.40±2.23)was higher than that in the myopic group(3.14±3.10; P<0.05). Patients in the myopic group had better near stereopsis than the non-myopic group(P<0.05). The non-myopic group had a variety of surgical methods, while the myopic group mostly used lateral rectus resection or/and medial rectus recession.CONCLUSION: AACE can occur in different refractive status. Non-myopic patients have the same degree of distant and near strabismus, high AC/A, and varied surgical methods. However, myopic patients have less degree of near deviation than distant deviation and have normal AC/A and better near stereopsis, and lateral rectus resection or/and medial rectus recession are commonly used.

OBJECTIVE: To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs. METHODS: The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot. RESULTS: The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05). CONCLUSION A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.
Humans ; Transforming Growth Factor beta1/pharmacology* ; Hepatic Stellate Cells/pathology* ; Liver Cirrhosis/genetics* ; Collagen Type I/pharmacology* ; RNA, Messenger/metabolism*

AIM: To compare the consistency and feasibility of objective ocular torsion measured with GMPE module-based optical coherence tomography(OCT)and fundus color photography(FCP).METHODS: Patients were enrolled in our strabismus clinic from December 2020 to March 2021, and the objective ocular torsion of the eyes was measured by both GMPE module-based OCT and FCP on the same day. FCP was used to measure the fovea-disc angle(FDA)manually by using the Adobe Photoshop software, while the GMPE module-based OCT software positioned automatically the macula and the center of the optic disc to measure the FDA.RESULTS: Fifty-five patients were included, the FDA measured by OCT was -6.6°±4.5° in the right eye and -8.8°±4.7° in the left eye, respectively; The FDA measured by FCP was -6.6°±4.7° in the right eye and -8.4°±4.1° in the left eye, respectively, with no statistically significant difference between the results of the two methods(Pright eye=0.90, Pleft eye=0.08). In patients with exotropia, the FDA measured by OCT was -5.8°±4.9° in the right eye and -9.1°±4.5° in the left eye, respectively, the FDA measured by FCP was -5.7°±5.0° in the right eye and -8.6°±4.3° in the left eye, respectively,(Pright eye=0.75, Pleft eye=0.15). Similarly, the patients with esotropia, the FDA measured by OCT was -9.0°±7.3° in the right eye and -11.3°±3.5° in the left eye, respectively, while the FDA measured by FCP was -10.0°±7.0° in the right and -10.1°±2.8° in the left eye(Pright eye=0.21, Pleft eye=0.10), respectively. There were no significant differences between the two methods in patients with esotropia or exotropia(P>0.05). The results of both Pearson test and Bland-Altman analysis were highly correlated(rright eye=0.93, rleft eye=0.94, P<0.01). CONCLUSION: GMPE module-based OCT can be used for objective ocular torsion measurement with high reliability and reproducibility, and is a promising clinical alternative to the fundus color photographic method.

Abstract: Objective　To explore the antiviral effect of baricitinib in the SARS-CoV-2 infection and influence on cytokine levels. Methods　Calu-3 cells were infected with SARS-CoV-2 at MOI of 0.1, and the levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-1β), interferon β (IFN-β) and interferon-stimulated gene, IFIT2 in the infected cells were analyzed by qRT-PCR methods. At the same time, Calu-3 cells were infected with SARS-CoV-2 (MOI=0.1) after being treated with baricitinib for 2 hours. Cells were collected at 0, 24, 36, and 48 hours, and analyzed for the mRNA of the above genes in the drug-treated and untreated groups. Results　The mRNA levels of IL-6, TNF-a, IL-1β, IFN-β and IFIT2 in Calu-3 infected by SARS-CoV-2 cells were increased significantly. These cytokines were increased by nearly 100-fold post-infection 48 h compared with the control (P<0.000 1), and continued to increase with the infection time (P<0.001 or P<0.000 1). The increase of IL-8 mRNA level was not as significant as IL-6, TNF-α, IL-8, IL-1β, but it also showed a 2-4 folds increase. Baricitinib does not affect the level of viral RNA in Calu-3 cells after SARS-CoV-2 infection (P>0.05). However, baricitinib can significantly inhibit the up-regulation of IL-6 and TNF-α levels induced by SARS-CoV-2 infection (5.25-fold and 3.90-fold down-regulation, respectively, P<0.01), and has little effect on the levels of IL-8 and IL-1β . In addition, the drug could also significantly down-regulate the increase in IFN-β and IFIT2 levels caused by viral infection (10.51-fold and 90.78-fold down-regulation, respectively, P<0.000 1). Conclusions　Baricitinib inhibits the release of inflammatory cytokines to some extent, but it drastically down-regulates the expression of interferons and interferon-stimulated genes (ISGs), and has limited antiviral effect on SARS-CoV-2. Considering that interferon signal pathways play important roles on viral infection, caution should be exercised when using baricitinib to treat COVID-19 patients.

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

Psoraleae Fructus is the dried and mature fruit of the legume Psoralea corylifolia. It is warm in nature， pungent and bitter in flavor， and attributive to the kidney and spleen meridians. Its main effect include warming the kidney and assisting Yang， absorbing Qi and relieving asthma， warming the spleen and relieving diarrhea， etc.， and it also can for external use of eliminating wind and freckle. Clinically， Psoraleae Fructus is mainly used for the treatment of impotence due to kidney deficiency， soreness of waist and knees， vitiligo， etc. The existing studies have shown that Psoraleae Fructus has a variety of pharmacological effect， such as anti-tumor， anti-oxidant， anti-bacterial， anti-inflammatory， promoting bone growth and protecting cardiovascular. But at the same time， many studies at home and abroad have found that taking Psoraleae Fructus and its compounds for a long time or in large doses can cause liver toxicity， phototoxicity， nephrotoxicity， etc. The most common is liver toxicity， most of the clinical reports on the toxicity of psoralen are caused by drug-induced liver injury events， which limits the clinical use of Psoraleae Fructus and can't exert its proper therapeutic effect. Therefore， it is particularly important to fully understand the toxicological mechanism of liver injury caused by Psoraleae Fructus and its attenuation methods. In this paper， by consulting the domestic and foreign related literatures in recent years that reported the hepatotoxicity of Psoraleae Fructus， the four aspects of clinical report on liver injury， hepatotoxic components， toxicological mechanisms and attenuation methods of Psoraleae Fructus were reviewed， including bile acid stasis and oxidative stress. The hepatotoxicity of Psoraleae Fructus was discussed in terms of reaction， mitochondrial damage， liver fat deformation， etc.， and the attenuation methods of Psoraleae Fructus were summarized from the aspects of compatibility attenuation and processing attenuation， aiming to comprehensively and objectively clarify Psoraleae Fructus. The potential toxicological mechanism of lipid-induced hepatotoxicity and research progress in attenuation were expected to provide a theoretical basis for further study of Psoraleae Fructus hepatotoxicity and clinical rational use of drugs.