BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95％ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P＜0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P＜0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P＜0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group＞human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group＞human umbilical cord blood mononuclear cell group＞human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group＞human umbilical cord blood platelet rich plasma group＞human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P＜0.001),and their expression levels decreased after treatment(all P＜0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P＜0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P＜0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P＜0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.

BACKGROUND:Whether activating transcription factor 7 interacting protein(Atf7ip)is involved in the regulation in osteogenic differentiation is still controversial,and studying its impact on osteogenic differentiation and its specific mechanisms is of great significance. OBJECTIVE:To investigate the effect of Atf7ip on bone morphogenetic protein 2 promoting osteogenic differentiation of mouse embryonic osteoblast precursor cells(MC3T3-E1). METHODS:MC3T3-E1 cells cultured in vitro were divided into three groups:normal group,interference group(NC-siRNA group,Atf7ip-siRNA group),and high expression group(CMV-VC group and CMV-Atf7ip group),and were transfected for 24 hours,and then treated with 200 ng/mL bone morphogenetic protein 2 for 0,12,24,and 48 hours,respectively.qRT-PCR was used to detect the mRNA expression levels of Atf7ip,alkaline phosphatase,osteocalcin,type I collagen α1 in the cells of each group.Western blot assay was used to detect the protein expression of osteogenic differentiation markers Sp7 and Runx2,and the expression of Atf7ip binding molecule SETDB1,histone H3 and H3K9me3.Alkaline phosphatase activity was detected by alkaline phosphatase staining. RESULTS AND CONCLUSION:(1)With the increase of bone morphogenetic protein 2 treatment time,the protein and mRNA expression of Atf7ip decreased,while the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and alkaline phosphatase increased significantly(P<0.05).There was no significant change in the protein expression of Atf7ip binding molecule SETDB1.(2)Compared with the NC-siRNA group,the protein expression of Sp7,Runx2 and the mRNA expression of osteocalcin and type I collagen α1 were significantly up-regulated(P<0.05),and alkaline phosphatase activity was significantly enhanced;and H3K9 methylation significantly decreased in the Atf7ip-siRNA group(P<0.05).(3)Compared with the CMV-VC group,the protein expression of Sp7 and Runx,as well as mRNA expression of osteocalcin,alkaline phosphatase,and type I collagen α1 was significantly downregulated(P<0.05),and the alkaline phosphatase activity was significantly reduced in the CMV-Atf7ip group,while the H3K9 methylation protein in the CMV-Atf7ip group was significantly upregulated compared to the control group(P<0.05).(4)In conclusion,Atf7ip expression was decreased during bone morphogenetic protein 2-induced osteogenic differentiation of MC3T3-E1,and osteogenic differentiation was significantly increased after knockdown of Atf7ip.Overexpression of Atf7ip significantly weakened osteogenic differentiation,indicating that Atf7ip is a negative regulatory factor of bone morphogenetic protein 2 promoting osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE To mine the adverse drug reaction （ADR） signals of melphalan， so as to provide reference for clinically safe drug use. METHODS Using OpenVigil 2.1 data platform， relative ADR reports of melphalan from the first quarter of 2004 to the second quarter of 2022 in FAERS database were collected； data mining was conducted using the reported odds ratio （ROR） method and Medicines and Healthcare Products Regulatory Agency （MHRA） method of disproportional method. ADR reports were described and classified according to the system organ class （SOC） and preferred term （PT） in Medical Dictionary for Regulatory Activities （24.0 edition）. RESULTS A total of 17 046 ADR reports related to the target drug melphalan were retrieved， and the number of ADR reports showed a fluctuating upward trend； the majority of patients were male （43.28%）， and were concentrated between the ages of 50-＜75 （35.09%）， with the main reporting country being the United States （23.97%）； ADR report involved a total of 22 842 severe outcomes， mainly including hospitalization or extended hospitalization （24.45%）. Totally 403 ADR signals were detected， involving 23 SOC， mainly including blood and lymphatic system diseases （801 cases， 13.77%）， followed by eye organ diseases （755 cases， 12.97%） and infectious and invasive diseases （716 cases， 12.30%）. The ADR signals ranked high in the number of reported cases included febrile neutropenia， diarrhea， fever and mucositis and other PT； PT such as pneumonia， sepsis， vitreous hemorrhage， chorioretinal atrophy， myelodysplastic syndrome were not recorded in drug instructions. The ADR signals with high signal strength ranking included choroidal dystrophy， chorioretinal atrophy， eyeball atrophy and other PT， and above three types of PT were not included in the drug instructions. CONCLUSIONS ADRs caused by melphalan mainly include blood and lymphatic system diseases， eye organ diseases， and infectious and invasive diseases； before using melphalan， it is necessary to evaluate the drug use of patients， and pay close attention to the patient’s blood indicators and eye toxicity reaction， so as to guarantee the safety of treatment.

Objective:To explore the teaching effect and novel ideas of online teaching applied in skill operation course.Methods:One hundred and fifty-one students studying in Sichuan University taking the First Aid in the Life: Basic Knowledge and Skills as an elective course in the autumn semester of 2019 and spring semester of 2020 were included as the research subjects in this study. Among them, 77 students in the spring semester of 2020 were selected as the experimental group and 74 students in the autumn semester of 2019 were selected as the control group. The students in the experimental group studied the first aid course by online platform, and the others in the control group studied through traditional teaching mode. The teaching effect of the two groups was compared and the teaching satisfaction of the two groups weas analyzed. SPSS 23.0 was used for Chi-square test and t-test. Results:There was no significant difference between the control group and the experimental group in the assessment scores of cardiopulmonary resuscitation, hemostatic bandaging, and fracture fixation [(8.65±0.81 vs 8.69±0.90, P=0.750); (8.10±0.50 vs 8.12±0.61, P=0.880); (8.21±0.89 vs 8.16±0.78, P=0.710)]. Among the students participating in the questionnaire survey in the experimental group, 59 (95.16%) students thought that this course was helpful in dealing with first aid in daily life, and 38 (61.29%) students did not want to change the traditional teaching method to online teaching. Conclusion:The application of online teaching in first-aid skill operation course is feasible and can achieve the similar teaching effect, which provides a novel idea for exploring the online teaching of first aid skills.

Objective To explore the diagnostic value of transcranial substantia nigra ultrasound in Parkinson's disease(PD)and the clinical characteristics of patients with different substantia nigra(SN)echoes.Methods Sixty patients with PD admitted to Yichun Hospital of Traditional Chinese Medicine from October 2020 to January 2023 were included in study group,and another 60 normal persons who received health examination in our hospital during the same period were included in control group.Both groups were examined by transcranial substantia nigra ultrasound.The SN high-echo area and ratio of total area of hyperechoic substantia nigra to total area of mesencephalon(S/M)of two groups were compared,and the positive rate of PD diagnosed by transcranial substantia nigra ultrasound was calculated.According to the intensity of SN echo,PD patients were divided into PD-SN-group and PD-SN+ group,and the clinical characteristics of patients with different SN echo were compared.Results The SN high-echo area and S/M of study group were significantly higher than those of control group(P<0.05).Transcranial substantia nigra ultrasound showed PD-SN-in 10 cases and PD-SN+ in 50 cases.The positive rate of PD diagnosed by transcranial substantia nigra ultrasound was 83.33%(50/60).There were statistically significant differences between PD-SN+ group and PD-SN-group in gender,age,H-Y stage,age of onset,score of mini mental status examination and score of Montreal cognitive assessment(P<0.05).Conclusion Transcranial substantia nigra ultrasound can better help clinical screening and detection of PD,and improve the positive detection rate of PD.

OBJECTIVE To excavate the risk signals of adverse drug events （ADEs） of atezolizumab after marketing， so as to provide a reference for rational use of atezolizumab. METHODS Using the FAERS database， the ADEs of atezolizumab were collected from marketing on May 18th 2016 to Mar. 31st 2022. The ADEs risk signals were mined by reported odds ratio （ROR） and medicines and Healthcare Products Regulatory Agency method （MHRA）， and then described and classified by preferred term （PT） and system organ classification （SOC） in the adverse drug reaction glossary of Medical Dictionary for Regulatory Activities （MedDRA） （23.0 edition）. RESULTS A total of 16 051 ADEs reports with atezolizumab as the primary suspected drug were collected， and 401 PT were mined， involving 17 SOC. In 16 051 ADEs reports， the majority of patients were male （51.64%）， with main age distribution of 19 to 64 years old and more than 65 years old. According to the number of reports， ADEs were mainly focusing on pyrexia， disease progression， interstitial lung disease， anaemia， pneumonia， etc. The involved SOC includes kidney and urinary system diseases， benign， malignant and unknown tumors （including cysts and polyps）， endocrine system diseases， etc. According to the signal intensity， the new ADEs not specified in the drug instructions were macular thickening， paraneoplastic neurological syndrome， reactive perforating collagenosis， paraneoplastic dermatomyositis， anti-erythrocyte antibody positive and liver sarcoidosis. CONCLUSIONS In addition to the ADEs mentioned in the drug instructions，when using atezolizumab in clinic，attention should also be closely paid to ADEs of eyes， nervous and skin system， so as to ensure the safety of drug use in patients.

Objective:To investigate the clinical application value of enhanced recovery after surgery using the LEER model in patients subjected to laparoscopic cholecystectomy in basic hospitals of Yi nationality area.Methods:Twenty-six patients who underwent laparoscopic cholecystectomy based on the concept of enhancing recovery after surgery using the LEER model in People's Hospital of Jinkouhe District of Leshan from January to October 2021 were included in the observation group. An additional 20 patients who concurrently underwent laparoscopic cholecystectomy and conventional intervention were included in the control group. Clinical efficacy, postoperative complications and postoperative pain were compared between the two groups.Results:Postoperative fasting time, length of hospital stay, and total hospital days in the observation group were 6 (6, 6) hours, 2 (2, 3) days and 4 (4, 6) days respectively, which were significantly shorter than 24 (24, 36) hours, 5 (5, 6) days, 7 (7, 9) days in the control group ( H = 351.00, 407.50, 458.00, all P < 0.05). Hospitalization cost in the observation group was 5 454.58 (5 014.11, 6 016.58) yuan, which was significantly lower than 6 611.91 (6 192.68, 7 841.73) yuan in the control group ( H = 420.00, P < 0.05). There were no significant differences in operative time and postoperative complications between the two groups (both P > 0.05). At postoperative 6 hours, Visual Analogue Scale score in the observation group was 3 (3, 4) points, and patients with mild pain accounted for 73.07% (19/26). At postoperative 24 hours, Visual Analogue Scale score in the observation group was 2 (2, 3) points, and patients with mild pain accounted for 92.31% (24/26). Overall pain was well controlled after surgery. Patient satisfaction rate in the observation was 96.15% (25/26). All patients recovered and were discharged. Conclusion:Application of enhanced recovery after surgery using the LEER model in patients subjected to laparoscopic cholecystectomy in basic hospitals of Yi nationality area can promote postoperative recovery, contribute to changing the theory of diagnosis and treatment, and improve overall medical quality. The enhanced recovery after surgery protocol using the LEER model has a good application value.

Objective:To investigate the impact of adding human menopausal gonadotropin (hMG) for in vitro fertilization-embryo transfer pregnancy outcomes in a standard population of non-advanced age with normal ovarian reserve function using a long follicular phase protocol.Methods:Clinical data of 489 patients with normal ovarian reserve function, who were admitted from January 2018 to January 2020 in the Affiliated Hospital of Guizhou Medical University and underwent in vitro fertilization for the first time with the long follicular phase protocol in fresh cycles, were retrospectively analyzed. The patients were divided into three groups according to whether or not to add urine-derived hMG and the timing of addition: non-addition group (group A), medium-term hMG group (group B1), whole course hMG group (group B2); the laboratory parameters of each group were observed, and the effect of ovulation induction drugs and pregnancy outcomes were compared.Results:The ages of B1 and B2 groups were significantly higher than that of group A ( P=0.019 and P=0.011). The basal FSH level of group B2 was significantly higher than those of group A and group B1 ( P<0.01 and P=0.006), and the basal FSH/LH ratio of group B2 was significantly higher than that of group B1 ( P=0.009). Antral follicle counts of group A and group B1 were significantly higher than that of group B2 ( P=0.007 and P=0.017). The superior embryo rate of group B2 [(47±27)%] was significantly higher than that of group A ( P=0.017). The embryo implantation rate of group B1 was significantly lower than those of group A and group B2 ( P=0.043 and P<0.01). The clinical pregnancy rate of group B2 [76.7% (155/202)] was significantly higher than those of group A ( P=0.039) and group B1 ( P<0.01). The live-birth rate of group B2 [67.3% (136/202)] was significantly higher than those of group A ( P=0.017) and group B1 ( P=0.001). Conclusions:For non-advanced aged patients with normal ovarian reserve function, the long protocol of follicular phase is suitable for those with relatively low ovarian reserve function. Adding hMG in the whole course of ovulation induction after gonadotropin-releasing hormone agonist reduction could improve the pregnancy outcomes by improving the quality of embryos.

Objective:To summarize the strategy of using extracorporeal membrane oxygenation (ECMO) support during lung transplantation from 2 coronavirus disease 2019 (COVID-19) with end-stage respiratory failure.Methods:Two COVID-19 with end-stage respiratory failure patients were admitted to Nanjing Medical University Affiliated Wuxi People's Hospital in March 2020. As the homoeostasis and vital signs could not be maintained in balance by conventional treatments, lung transplantations were performed. Here, detail information about combined application of peripheral veno-venous ECMO (VV-ECMO) and central veno-arterial ECMO (CVA-ECMO) during the operation will be discussed.Results:Case 1: 59 years old, 172 cm height, 72 kg weight, who received mechanical ventilation for 22 days, tracheotomy tube for 17 days, and VV-ECMO support for 7 days. Case 2: 72 years old, 178 cm height, 71 kg weight, who received mechanical ventilation for 19 days, tracheotomy tube for 17 days, and VV-ECMO support for 18 days. As both of them have severe COVID-19-associated respiratory failure, and the recovery was determined to be unlikely, lung transplantations were performed. Severe pulmonary arterial hypertension (PAH) and cardiac insufficiency were found during the operation. Based on preoperative VV-ECMO, CVA-ECMO was added. The concomitant use of peripheral VV-ECMO and CVA-ECMO offered satisfied intraoperative oxygenation and cardiopulmonary status, the operations run smoothly, and the CVA-ECMO was successfully removed, no ECMO-related complications occurred.Conclusion:The combined use of VV-ECMO and CVA-ECMO is an optimal strategy in the end-stage ARDS patients with severe PAH and cardiac insufficiency, which can offer benefits on respiratory and cardiac functions simultaneously, and ensure surgery safety.