Objective:To evaluate the role of reactive oxygen species (ROS) in attenuation of hypoxia-reoxygenation (H/R) injury in rat cardiomyocytes by pinacidil postconditioning and the relationship with nuclear factor erythrid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway.Methods:Adult rat cardiomyocytes were isolated and cultured and then divided into 4 groups ( n=20 each) by a random number table method: control group (group C), H/R group, pinacidil postconditioning group (group P) and reactive oxygen scavenger N-(2-mercaptopropionyl)-glycine(MPG)+ pinacidil postconditioning group (group MPG+ P). Group C was continuously exposed to 95%O 2+ 5%CO 2 in an incubator at 37 ℃ for 105 min. The cells were exposed to 5%CO 2+ 1%O 2+ 94%N 2 in an incubator at 37 ℃ for 45 min followed by reoxygenation for 60 min to prepare H/R injury model. The cells were exposed to hypoxia for 45 min and then treated with pinacidil 50 μmol/L for 5 min followed by reoxygenation for 60 min in group P. The cells were exposed to hypoxia for 45 min, treated with MPG 2 mmol/L for 10 min, and then treated with pinacidil for 5 min followed by reoxygenation for 60 min in group MPG+ P. The content of Ca 2+ and activity of Nrf2 in cardiomyocytes were measured at the end of reoxygenation. The ultrastructure of cardiomyocytes was observed, and mitochondrial ultrastructure was evaluated using mitochondrial Flameng score. The expression of Nrf2, superoxide dismutase (SOD1), quinone oxidoreductase 1 (NQO1), and heme oxygenase 1 (HO-1) protein and mRNA was detected using Western blot and real-time polymerase chain reaction. Results:Compared with group C, the Ca 2+ content, Nrf2 activity and mitochondrial Flameng score were significantly increased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the damage to the ultrastructure of cardiomyocytes was aggravated in group H/R. Compared with H/R group, the Ca 2+ content and mitochondrial Flameng score were significantly decreased, the Nrf2 activity was increased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the damage to the ultrastructure of cardiomyocytes was attenuated in P group. Compared with P group, the Ca 2+ content and mitochondrial Flameng score were significantly increased, the Nrf2 activity was decreased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the damage to the ultrastructure of cardiomyocytes was aggravated in MPG+ P group. Conclusions:ROS is involved in attenuation of H/R injury by pinacidil postconditioning, which is associated with activation of the Nrf2-ARE signaling pathway in rat cardiomyocytes.

ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine（TCM）. By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos， Houttuyniae Herba injection， Lonicerae Japonicae Flosand Buyang Huanwutang， this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship， namely half-life， statistical moment and statistics， in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group， and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling， the mice were gavaged with aqueous extract of Lonicerae Flos（30 g∙kg^-1）， and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time， the pharmacokinetic results of Houttuyniae Herba injection， Lonicerae Japonicae Flos and Buyang Huanwutang were included， and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method， statistical moment method and statistical method was compared. ResultOn the basis of the half-life method， the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied， with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity， the metabolic patterns among the components contained in Houttuyniae Herba injection， Lonicerae Japonicae Flos， Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method， statistical moment method and statistical method， and it was found that the difference between statistical moment method and half-life method was large， and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method， characterizes the dispersion degree of each component， but also can be associated with fingerprint to form spectrokinetics， characterizing the dose-time relationship of 95% of drug components， which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

Methods: This study established the MFSM method. To demonstrate its effectiveness, we applied this novel approach to analyze Danxi Granules (丹膝颗粒, DXG) and its constituent herbal materials. To begin with, the ultra-performance liquid chromatography (UPLC) was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materials. Next, the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units. Then, we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment (TQSM) parameters, information entropy and information amount, along with their relative standard deviation (RSD). Finally, we compared the TQSM parameters, information entropy and information amount, and their RSD between the traditional and novel fingerprints to validate the new analytical method. Results: The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method. Before integration, the ranges of the peak number, three TQSM parameters, information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07 − 209.73, 9390 − 183064 μv·s, 5.928 − 21.33 min, 22.62 − 106.69 min2, 4.230 − 6.539, and 50530 − 974186 μv·s, respectively. After integration, the ranges of these parameters were 10.00 − 88.00, 9390 − 183064 μv·s, 5.951 − 22.02 min, 22.27 − 104.73 min2, 2.223 − 5.277, and 38159 − 807200 μv·s, respectively. Correspondingly, the RSD of all the aforementioned parameters before integration were 2.12% − 9.15%, 6.04% − 49.78%, 1.15% − 23.10%, 3.97% − 25.79%, 1.49% − 19.86%, and 6.64% − 51.20%, respectively. However, after integration, they changed to 0.00%, 6.04% − 49.87%, 1.73% − 23.02%, 3.84% − 26.85%, 1.17% − 16.54%, and 6.40% − 48.59%, respectively. The results demonstrated that in the newly integrated fingerprint, the analytical units of constituent herbal materials, information entropy and information amount were significantly reduced (P < 0.05), while the TQSM parameters remained unchanged (P > 0.05). Additionally, the RSD of the TQSM parameters, information entropy, and information amount didn’t show significant difference before and after integration (P > 0.05), but the RSD of the number and area of the integrated analytical units significantly decreased (P < 0.05). Conclusion The MFSM method could reduce the analytical units of constituent herbal materials while maintain the properties and variability from their original fingerprint. Thus, it could serve as a feasible and reliable tool to reduce difficulties in analyzing multi-components within CMMs and facilitating the evaluation of their quality.

Objective:To analyze the clinical features and genetic basis of a child with Disorder of sex development (DSD).Methods:A child who was admitted to the Linyi People′s Hospital for primary amenorrhoea on July 29, 2019 was selected as the study subject. Clinical data of the child was collected. Chromosomal karyotyping and quantitative real-time PCR were used to detect Y chromosome microdeletions and other chromosomal aberrations. Next-generation sequencing was carried out for the child and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 13-year-old girl, has featured primary amenorrhoea and onset of secondary sex characteristics of males. Ultrasound exam had detected no uterus and definite ovarian structure, but narrow band vaginal hypoecho and curved cavernoid structure. The child was found to have a 46, XY karyotype without an AZF deletion. DNA sequencing revealed that she has harbored a maternally derived c. 323delA (p.Q108Rfs*188) variant in the nuclear receptor subfamily 5 group A member 1 ( NR5A1) gene, which may result in a truncated protein. The variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion:The NR5A1: c. 323delA variant probably underlay the pathogenesis of 46, XY DSD in this child. The discovery of the novel variant has enriched the mutational spectrum of NR5A1 gene and provided a basis for clinical diagnosis, treatment and prenatal diagnosis.

Objective:To analyze the clinicopathological features of de novo early colorectal cancer and to evaluate the efficacy of endoscopic treatment.Methods:Patients with de novo early colorectal cancer who underwent endoscopic resection in Beijing Friendship Hospital, Capital Medical University from June 2020 to May 2022 were enrolled. The baseline data, endoscopic manifestations, treatment methods, postoperative pathological results and prognosis of the patients were collected retrospectively.Results:A total of 33 patients with de novo early colorectal cancer were enrolled with the age of 62.67 ± 8.62 years, and the male to female ratio was 7.25∶1. The long diameter of lesions was 0.96 ± 0.36 cm. The lesion morphology was mainly superficial phenotype (type 0-Ⅱ), accounting for 72.7% (24/33). Endoscopic submucosal dissection (ESD) was performed in 29 cases and endoscopic mucosal resection (EMR) was performed in 4 cases. Postoperative pathology showed that 11 cases (33.3%) were well differentiated tubular adenocarcinoma, of which the superficial submucosal layer was invaded in 2 cases. Twenty cases (60.6%) were moderately differentiated tubular adenocarcinoma, of which the superficial submucosa layer was invaded in 5 cases and the deep submucosa layer in 15 cases. Two cases (6.1%) were moderately-poorly differentiated tubular adenocarcinoma, where the deep submucosa layer was invaded in both. There was significant correlation between the depth of invasion and the degree of differentiation ( P<0.001), and moderately and moderately-poorly differentiated lesions were more likely to invade the deep submucosa layer. The en bloc resection rate was 100.0% (33/33), the complete resection rate was 97.0% (32/33), and the curative resection rate was 42.4% (14/33). Among the 19 patients who did not achieve curative resection, 13 patients received supplementary surgical treatment. No tumor residue or lymph node metastasis was found in the postoperative pathology. All patients were followed up for 3-25 months, and no signs of local recurrence or metastasis were found. Conclusion:Most de novo early colorectal cancers are superficial phenotype under endoscopy. The pathology is mainly moderately differentiated tubular adenocarcinoma. Endoscopic resection of de novo early colorectal cancer shows encouraging short-term efficacy.

Objective:To identify two pathogenic gene mutations in two families with Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. Two patients and five family members from two Han families of ALMS diagnosed at Henan Eye Hospital from August 2020 to December 2021 were enrolled in this study. All participants underwent comprehensive ophthalmic examinations including best corrected visual acuity (BCVA), color test, slit-lamp, fundus biomicroscopy with slit lamp, fundus color photography, optical coherence tomography (OCT) and full-field electroretinography (ff-ERG) after the detailed history of the patient was taken. Five millilitres peripheral venous blood of each subject was collected, and the whole genome DNA was extracted. The pathogenic genes and mutation sites were identified using whole exome sequencing and the identified mutations were verified by Sanger sequencing. Mutation sites were analyzed via bioinformatics softwares.Results:Family one included one victim and two members and family two included one victim and three members. Proband in the first family was a four-year old boy whose chief complaint was poor vision along with photophobia since born, while proband in the second family was a 12-year old girl whose chief complaint was the same. The boy proband could not distinguish color, and both the anterior segment and fundus were normal. Ellipsoid zone of the boy was unclear in both eyes in OCT, and though rod system function decreased mildly-moderately in both eyes, the cone system function decreased severely in ff-ERG. The girl could not distinguish color as well, and the anterior segment was normal, though obvious pigmentary change could be seen in both retinas. The integrity of outer retinal bands was unclear in both eyes in OCT, and both cone and rod systems function decreased severely in both eyes in ff-ERG. Gene tests and bioinformatics analyze showed c.468dupT and c.10819C>T of ALMS1 gene in family one were novel mutations and c.10819C>T in family one and c.10831_10832del in family two were pathogenic mutations. Conclusions:M1, M2 and M3, M4 may be pathogenic gene variants in family 1 and family 2, respectively. The compound heterozygous mutation, c.468dupT and c.10819C>T of ALMS1 gene was a novel mutation.

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.

Objective To conduct a scoping review on studies of tele-health management for stroke patients at home.Methods According to the reporting framework of scoping review,a system-atic literature search was performed in 9 databases or websites from January 1,2013 to May 1,2023.Results A total of 52 literatures from 12 countries were included,most of which were interventional studies.Tele-health management was gradually becoming a trend in the application of stroke patients at home,relying on rehabilitation robots,virtual reality rehabilitation games,social platforms,home health network platforms and other carriers for rehabilitation training,disease monitoring,health edu-cation and guidance,follow-up and reminder.Conclusion The contents of tele-health management for stroke patients at home are abundant,with many evaluation indexes.In the future,rehabilitation training should enhance the gameplay of rehabilitation video games,improve patient's experience,and use artificial intelligence based on medical big data to provide auxiliary support for patients;at the same time,the content of each module of the tele-health management program should be standardized,and caregivers are encouraged to participate in the tele-health management of stroke patients at home,so as to better play the role of tele-health management in the field of post-stroke health management at home.

Objective To conduct a scoping review on studies of tele-health management for stroke patients at home.Methods According to the reporting framework of scoping review,a system-atic literature search was performed in 9 databases or websites from January 1,2013 to May 1,2023.Results A total of 52 literatures from 12 countries were included,most of which were interventional studies.Tele-health management was gradually becoming a trend in the application of stroke patients at home,relying on rehabilitation robots,virtual reality rehabilitation games,social platforms,home health network platforms and other carriers for rehabilitation training,disease monitoring,health edu-cation and guidance,follow-up and reminder.Conclusion The contents of tele-health management for stroke patients at home are abundant,with many evaluation indexes.In the future,rehabilitation training should enhance the gameplay of rehabilitation video games,improve patient's experience,and use artificial intelligence based on medical big data to provide auxiliary support for patients;at the same time,the content of each module of the tele-health management program should be standardized,and caregivers are encouraged to participate in the tele-health management of stroke patients at home,so as to better play the role of tele-health management in the field of post-stroke health management at home.

Objective:To evaluate the role of reactive oxygen species (ROS) in hypoxia postconditioning-induced activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway in rat cardiomyocytes.Methods:Primary cardiomyocytes of adult rats were isolated and cultured and divided into 4 groups ( n=20 each) using a random number table method: normal group (group N), hypoxia-reoxygenation group (group HR), hypoxia postconditioning group (group HPO) and hypoxia postconditioning plus an ROS scavenger N-(2-Amidinopropionyl)-glycine (MPG) group (group HPO+ MPG). Cells were exposed to hypoxia for 45 min followed by 60 min reoxygenation to develop the cardiomyocyte hypoxia-reoxygenation injury model.In HPO group, cells were subjected to 3 cycles of 5-min hypoxia/5-min reoxygenation after 45 min hypoxia, followed by reoxygenation for 60 min.In HPO+ MPG group, MPG (final concentration 2 mmol/L) was added at 35 min of hypoxia, cells were subjected to hypoxia for 10 min, and the other treatments were similar to those previously described in group HPO.At the end of reoxygenation, the intracellular calcium level and Nrf2 activity were measured, the ultrastructure of cardiomyocytes was observed, and the Flameng score of mitochondria was assessed, and the expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (NQO1), superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1) protein and mRNA was detected using real-time polymerase chain reaction and Western blot. Results:Compared with group N, the intracellular free Ca 2+ level, Nrf2 activity and Flameng score were significantly increased, and the expression of Nrf2, NQO1, SOD1 and HO-1 protein and mRNA was down-regulated in group HR ( P<0.05). Compared with group HR, the intracellular free Ca 2+ level and Flameng score were significantly decreased, the Nrf2 activity was increased, and the expression of Nrf2, NQO1, SOD1 and HO-1 protein and mRNA was up-regulated in group HPO ( P<0.05). Compared with group HPO, the intracellular free Ca 2+ level and Flameng score were significantly increased, the Nrf2 activity was decreased, and the expression of Nrf2, NQO1, SOD1 and HO-1 protein and mRNA was down-regulated in group HPO+ MPG ( P<0.05). Conclusions:The mechanism by which hypoxia postconditioning activates the Nrf2/ARE signaling pathway in rat cardiomyocytes may be related to ROS.