Objective To explore the CT manifestations and clinical features of checkpoint inhibitor-related pneumonitis(CIP).Methods Chest CT images and clinical data of 34 patients with CIP in Ningbo No.2 Hospitael were collected to retrospectively analysis.According to the site of tumor occurrence,22 patients were divided into lung cancer group and 12 patients in other malignant tumor group,and the differences in CT manifestations between two groups were compared.Results Cough(70.59％)and dyspnea(52.94％)were the common clinical symptoms.CIP occurred earlier and over a greater time span in lung cancer group 114.5(41.50,281.50)d than in other maligment tumor group 144(55.75,226.25)d.Eosinophil count was significantly higher only in other maligment tumor group(P=0.009).After hormonal therapy 18 patients improved,8 were stable and 8 progressed or even died.CT signs were prevalent in ground glass shadow(70.59％)and solid shadow(76.47％),and the imaging pattern was dominated by organic pneumonia pattern(47.6％),which was not related to type of primary tumor,and some of them could show nodular granulomatous reaction.Compared to lung cancer group,the other maligment tumor group was more likely to exhibit symmetrical infiltration(58.33％)distribution.Conclusion The clinical features of CIP are nonspecific,compared with other patients with primary malignancies,lung cancer patients are more likely to develop CIP,which is difficult to relieve after treatment,and are easy to develop severe disease.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

Objective:To explore the mechanism of Shuerjing Capsule in treating primary dysmenorrhea based on molecular docking of network pharmacology and in vivo experiment.Methods:By using TCMSP to screen the active components and targets of Shuerjing Capsule; by using GeneCards and DrungBank databases to retrieve targeted proteins of primary dysmenorrhea, and the intersection targets of drugs and diseases were obtained through Weishengxin online platform; by using Cytoscape 3.9.1 software to produce component-target network of Shuerjing Capsule for the treatment of primary dysmenorrhea; by STRING databases to construct drug-disease target PPI network; by DAVID database to perform GO and KEGG pathway enrichment analysis.The key active components of the drug and the core targets of the disease were obtained with molecular docking. The rats were randomly divided into control group, model group, the low-dose group, medium-dose group and high-dose group of Shujing Capsule (0.15, 0.21, 0.42 g/kg), and ibuprofen group (20 mg/kg), with 10 rats in each group. The animal model of primary dysmenorrhea was established by subcutaneous injection of estradiol benzoate and intervented by drugs. The number of writhing reaction, uterine contractile inhibition rate and uterine index of rats were observed. The expressions of TNF-α, IL-6 and IL-1 in serum and the levels of PTGS2 and VEGFA in uterine tissue were detected by ELISA.Results:A total of 188 active ingredients of Shuerjing Capsule were screened, and 51 targets of Shuerjing Capsule and primary dysmenorrhea were identified. TNF, IL-6, AKT1 and TP53 may be the key targets of Shuerjing Capsule in the treatment of primary dysmenorrhea. A total of 519 GO biological processes and 119 related signaling pathways were obtained, among which estrogen, IL-17, HIF-1 and other signaling pathways were closely related to the treatment of primary dysmenorrhea. The results of molecular docking were good, among which stigmasterol had the strongest binding ability to TP53. The experimental results showed that compared with the model group, the uterine index and the number of torsion were decreased in the low -, medium - and high-dose Shuojing Capsule groups ( P<0.05), the uterine contraction inhibition rate increased ( P<0.05); Serum levels of TNF-α, IL-6 and IL-1 of medium and high dose group decreased ( P<0.05), the levels of PTGS2 and VEGFA in uterine tissues decreased ( P<0.05). Conclusion:Shuerjing Capsule has the effect of anti-inflammatation and improveing hypoxia, which may be related to the inhibition of TNF-α, IL-6 and IL-1 inflammatory factors in serum and the expression of PTGS2 and VEGFA proteins in uterine tissues.

The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.

ObjectiveTo investigate the protective effect of fecal microbiota transplantation (FMT) on mice with acute-on-chronic liver failure (ACLF) and its effect on intestinal flora. MethodsA total of 40 mice were randomly divided into control group (CON group), model group (MOD group), FMT group (feces of the mice in the CON group were used as fecal microbiota donor), and FMT model group (ANFMT group, with feces of the mice in the MOD group as fecal microbiota donor), with 10 mice in each group. All mice were observed in terms of body weight, death, liver histopathology, and changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and intestinal flora. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. ResultsCompared with the CON group, the MOD group had a significant reduction in body weight and significant increases in AST and ALT (all P＜0.05), as well as large patchy necrosis of hepatocytes, significant increases in Verrucomicrobia, Akkermansia, and Erysipelatoclostridium, and significant reductions in Dubosiella and Duncaniella (all P＜0.05). Compared with the CON group, the ANFMT group had a significant increase in AST (P＜0.05), hepatocyte swelling and mild ballooning degeneration, significant increases in Unclassified and Faecalibaculum, and significant reductions in Patescibacteria, Deferribacteres, Muribaculum, Candidatus_Saccharimonas, Rikenella, Odoribacter, Mucispirillum, and Lachnospiraceae_unclassified (all P＜0.05). Compared with the MOD group, the FMT group had significant reductions in AST and ALT (both P＜0.05), mild hepatocellular necrosis and marked ballooning degeneration, significant increases in Paramuribaculum and Bilophila, and significant reductions in Firmicutes, Rikenella, and Absiella (all P＜0.05). ConclusionIntestinal flora disturbance is observed in ACLF mice, and dysbacteriosis may lead to liver injury. FMT can alleviate liver inflammation in ACLF mice and thus exert a protective effect.

It is an important way to improve the teaching quality by carrying out innovative experiments among medical students. In the process of experimental teaching, anatomy teachers expand the anatomy knowledge to basic scientific research techniques, so as to enhance students' confidence in participating in innovative experimental projects. Meanwhile, the teachers combine introduction of the anatomical structures with hot medical research issues, in order to help students to select appropriate innovative experimental topics. What's more, the new media teaching is integrated into the teaching of anatomy, enlightening students to perfect the experimental designs. Finally, in the teaching practice of regional anatomy, students are guided to carry out innovative experiments and write research papers. Abovementioned measures not only improve the teaching quality of anatomy, but also improve the students' scientific research ability, laying a foundation for them to participate in innovative experimental projects.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Objective To determine ED50 and ED9 5 of etomidate for combined remifentanil used in elderly patients in gastroscope.Methods Twenty-three patients were scheduled to receive gastros-copy aged 65-78 years old including males 13 and females 10,weighting 45-76 kg and ASA Ⅰ-Ⅲ. They were slowly injected remifentanil 0.3 μg/kg,and then etomidate 0.20 mg/kg,gastroscopy was performed after their eyelash reflex disappeared.The dosage of etomidate were determined by modified up-and-down methods,0.20 mg/kg was initial dosage.During the gastroscope,restlessness, frowning,swallowing,choking cough could be seen.The adjacent experimental interval dosage was 0.05 mg/kg,the trial was ended when there was the seventh cross-sectional,and determined the ED50 and ED9 5 of etomidate and (95%confidence interval)of them for gastroscope with probability a-nalysis methods.Results The ED50 of etomidate was 0.1 7 mg/kg and 95%CI 0.14-0.21 mg/kg,and the ED9 5 was 0.23 mg/kg,95%CI 0.20-0.42 mg/kg respectively.Conclusion The ED50 and ED9 5 of etomidate combined with remifentanil used for elderly patients for gastroscope respectively are 0.1 7 mg/kg and 0.23 mg/kg.

Background Researches showed that femtosecond laser corneal small incision lenticule extraction (SMILE) was used in the correction of myopia and myopic astigmatism due to its fast recovery,good shortterm efficacy and few complications.However,few research focused on its long-term efficacy.Objective Thisstudy was to evaluate the effectiveness,safety,predictability,stability and complications of SMILE.Methods A serial cases-observational study was carried out under the approval of Ethic Committee of Henan Eye Institute and informed consent of patients.Sixty-seven eyes of 34 patients with myopia and myopic astigmatism were included in Henan Eye Institute from January to June 2013.All the patients received SMILE and followed-up for 2-year duration.The uncorrected visual acuity (UCVA),best corrected visual acuity (BCVA),automatic optometry,intraocular pressure and corneal topography were examined before surgery and 1 day,1 week,1 month,3 months,1 year and 2 years after surgery and calculated the spherical equivalent (SE).The long-term efficacy of SMILE included effective index (preoperative BCVA/postoperative UCVA),safety index (postoperative BCVA/ preoperative BCVA),predictability (linear regression analysis between actual SE and attempted SE) and refractive stability (SE changes at postoperative time points).Results The preoperative BCVA was ≥ 20/20 in 60 eyes with the percentage of 89.55％.UCVA≥ 20/20 were found in 61 eyes and 60 eyes in postoperative 3 months and 2 years respectively (91.04％ and 89.55％).The effective index was 1.038±0.182 and 1.029±0.231 in postoperative 3 months and 2 years respectively,showing an insignificant difference between them (t =0.400,P ＞ 0.05).Compared with the preoperative BCVA,8.96％ (6/67) and 10.45％ (7/67) eyes lost 1 line at 3 months and 2 years after surgery,respectively.The safety indexes were 1.141±0.193 and 1.312±0.242 at 3 months and 2 years after surgery,with no significant difference between them (t =0.414,P＞0.05).A linear correlation was found between actual SE and attempted SE both at postoperative 3 months and 2 years,with the linear regression equations of Y=0.897 1X-0.440 8 (R2 =0.914 2,P＜0.05) and Y =0.893 7X-0.382 3 (R2 =0.915 7,P＜0.05),respectively.The SE was (0.013±0.578),(-0.033±0.489),(-0.106±0.508),(-0.103±0.375),(-0.154±0.518) and (-0.147±0.366)D 1 day,1 week,1 month,3 months,1 year and 2 years after surgery,respectively,and there were no significant difference among different time points (F =0.185,P =0.176).Eighteen in the 67 eyes occurred opaque bubble layer after surgery.Diffuse lamellar keratitis appeared in 6 eyes and punctate keratitis was in 2 eyes.These complications were cured 1 month after administration of drugs.Conclusions SMILE is good in effectiveness,safety,predictability and refreactive stability and has fewer complications during 2-year following-up.