Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.
Real-Time Polymerase Chain Reaction/methods* ; Paeonia/genetics* ; Actins/genetics* ; Reproducibility of Results ; Transcriptome ; Glyceraldehyde-3-Phosphate Dehydrogenases/genetics* ; Reference Standards ; Gene Expression Profiling/methods*

Objective:To compare the efficacy and safety of preoperative and postoperative concurrent chemoradiotherapies in the treatment of stage Ⅲ-Ⅳ A gastric cancer patients who underwent D2 lymphadenectomy with R0 resection. Methods:A retrospective analysis was conducted on the clinical data of patients with stage Ⅲ-Ⅳ A gastric cancer who underwent D2 lymphadenectomy with R0 resection in the Affiliated Cancer Hospital of Zhengzhou University from 2012 to 2019. Among these patients, 25 received preoperative chemoradiotherapy (group A) and 22 received postoperative chemoradiotherapy (group B). The disease-free survival (DFS), overall survival (OS), local recurrence rate, distant metastasis rate, and adverse reactions were compared between both groups. The total dose, single dose, fractions, and duration of radiotherapy for all the patients were 45-50.4 Gy, 1.8-2.0 Gy, 25-28 fractions, and 5-6 weeks, respectively. The target areas were delineated in accordance with the ASTRO and EORTC-ROG guidelines. Results:There was no statistical difference in clinical baseline characteristics between the two groups. The median follow-up was 48 months (3-72 months). The 1-year OS of group A was significantly higher than that of group B (92% vs. 54.5%, χ2= 5.68, P = 0.017). The 3-year OS and DFS of the two groups were 56% vs. 40.9% ( P> 0.05) and 51.4% vs. 31.8% ( P> 0.05), respectively. There was no significant difference in the local recurrence rate between both groups ( P> 0.05), but the distant metastasis rate of group A was significantly lower than that of group B ( χ2= 6.01, P = 0.014). There was no significant difference in digestive side effects and myelosuppression between both groups ( P> 0.05). Conclusions:For patients with stageⅢ-Ⅳ A gastric cancer after D2 lymphadenectomy with R0 resection, the preoperative and postoperative chemoradiotherapies yield similar efficacy and safety. However, compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy improves the 1-year OS and reduces the distant metastasis rate.

Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.

Objective:To investigate the preparation methods and quality control of 177Lu-labeled radiopharmaceuticals, and conduct preliminary clinical application research. Methods:177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-Phe1-Tyr3-octreotide (TOC) and 177Lu-prostate specific membrane antigen (PSMA)-I&T were labeled by manual labeling and automatic labeling, respectively. Factors such as the amount of precursor and nuclide, reaction temperature, pH value, reaction time, labeling yield and specific activity were investigated. Quality control of the products were carried out, such as clarity, pH value, sterility, bacterial endotoxin and stability in vitro. 177Lu-PSMA-I&T was applied to the treatment of prostate cancer patients, and the efficacy was evaluated by SPECT/CT imaging. Paired t test was used to analyze the data. Results:The amount of precursor and nuclide, reaction temperature, pH value and reaction time of the two methods were basically the same, both with high yield and specific activity. The yield of 177Lu-DOTA-TOC automatic labeling was significantly higher than that of manual labeling (99.2±0.4)% vs (95.3±1.5)% ( t=7.17, P<0.001), and the specific activity were (91.6±13.7) vs (89.1±13.2) GBq/μmol. The yield of 177Lu-PSMA-I&T automatic labeling was also significantly higher than that of manual labeling (99.6±0.3)% vs (95.7±1.3)% ( t=8.24, P<0.001), and the specific activity were (96.1±14.3) vs (93.2±13.8) GBq/μmol. The labeled products were colorless clear solution with pH value of 6.5-7.0. The sterility and bacterial endotoxin met the requirements. The radiochemical purity of the labeled products was more than 95% after 48 h, which showed good stability. The clinical application of 177Lu-PSMA-I&T in patients with prostate cancer showed that both primary and metastatic lesions had good uptake. Conclusions:The labeling of 177Lu radiopharmaceuticals is simple and has high yield and stability. The application of automatic labeling can simplify the process, improve the yield and reduce irradiation.

Objective:To investigate the spectrum of amino acid, organic acid, and fatty acid oxidative metabolic diseases in children diagnosed by detecting urinary organic acid levels using gas chromatography-mass spectrometry.Methods:From January 2005 to December 2021, clinical data of 2 461 children diagnosed with inherited metabolic diseases (IMD) by gas chromatography-mass spectrometry, in combination with tandem mass spectrometry and genetic testing in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed.Results:Among 2 461 children, 1 446 were male and 1 051 were female. A total of 32 types of IMD were detected among 2 461 patients, which included 10 amino acid disorders in 662 cases (26.9%), 6 common diseases were hyperphenylalaninemia, citrin deficiency, ornithine carbamoyltransferase deficiency, maple syrup urine disease, alkaptonuria, and tyrosinemia-I, 17 types of organic acidemias in 1 683 cases (68.4%), 6 common diseases were methylmalonic acidemia, propionic acidemia, valeric acidemia-type Ⅰ, isovaleric acidemia, 3-methylcrotonyl-CoA carboxylase deficiency and multiple carboxylase deficiency and 5 fatty acid β oxidative defects in 116 cases (4.7%), 2 common diseases were multiple acyl-CoA dehydrogenase deficiency and short-chain acyl-CoA dehydrogenase deficiency).Conclusion:Among the diseases diagnosed by analyzing urinary organic acid profiling with gas chromatography-mass spectrometry, the most common are organic acidemias, followed by amino acid disorders and fatty acid oxidation defects.

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （P<0.05， P<0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （P<0.05， P<0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1β， IL-6 and TNF-α in the hippocampus of the model group increased significantly as compared with the blank control group （P<0.05， P<0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （P<0.05， P<0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1β remarkably increased in the model group （P<0.05， P<0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1β was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （P<0.05， P<0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

OBJECTIVE: To investigate and compare the clinical efficacies of remnant-preserving and remnant-non-preserving, remnant-non-preserving remnant segment preserving and remnant root preserving with anterior cruciate ligament reconstruction. METHODS: From March 2014 to December 2017, 204 patients with anterior cruciate ligament (ACL) injuries were treated by single-bundle ACL reconstruction with hamstring tendon autograft. According to the different methods of remnant preservation, the procedures were divided into remnant segment preserving group (A), remnant root preserving group (B), and remnant-non-preserving group (C). There were 37 males and 39 femalesin group A aged from 16 to 43 years old with an average of (28.80±5.41) years old. The time from injury to operation ranged from 2 to 11 weeks with an average of (3.68±1.04) weeks. In group B, there were 39 males and 25 females aged from 18 to 41 years old with an average of (28.42±5.60) years old. The time from injury to operation ranged from 2 to 10 weeks with an average of (3.36±1.68) weeks. In group C, there were 37 males and 27 females aged from 18 to 43 years old with an average of (29.10±6.11) years old. The time from injury to operation ranged from 3 to 11 weeks with an average of (3.54±1.46) weeks. The range of motion (ROM) of the knee was used to assess the range of extension and flextion of the knee at pre-operation and 24 months after operation. Lysholm score and the international knee documentation committee (IKDC) score were used to assess the knee function. The differences among three procedures were judged by comparing among the three groups at 6, 12 and 24 months postoperatively. RESULTS: All incisions got a one stage healing, and no complications, such as vascular injury, nerve damage and articular infect or the like, occurred. All the patients were followed up, and the follow-up duration of group A ranged from 24.00 to 45.96 months with a mean of (35.52±14.40) months;the follow up duration of group B ranged from 27.96 to 48.00 months with a mean of (37.56±10.68) month;and the follow up duration of group C ranged from 24.00 to 66.00 months with a mean of (37.08±13.44) month. There were no significant differences in follow up time among three groups ( CONCLUSION Compared with remnant-non-preserving group, the residual tissue of anterior cruciate ligament is preserved, which is conducive to promote the healing and remodeling of tendon graft and accelerate the recovery of joint function. Proper fixation of residual tissue and restoration of its tension are the key factors affecting the postoperative efficacy.
Adolescent ; Adult ; Anterior Cruciate Ligament/surgery* ; Anterior Cruciate Ligament Injuries/surgery* ; Anterior Cruciate Ligament Reconstruction ; Arthroscopy ; Case-Control Studies ; Female ; Humans ; Knee Joint/surgery* ; Male ; Treatment Outcome ; Young Adult