Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells

BACKGROUND@#Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. @*METHODS@#hUCMSCs were isolated from Wharton’s jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. @*RESULTS@#SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2–related factor 2 signaling. @*CONCLUSION@#These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

Application of multimodal electromagnetic navigation in endoscopic endonasal skull base anatomical measurement of fresh cadavers / 解剖学报

Objective Electromagnetic navigation was used to observe and measure important anatomical structures through endoscopic endoscopic approach (EEA) to the ventral skull base to provide data for clinical surgery. Methods Using electromagnetic navigation to measure the anatomical structure of the central and paracentral ventral skull base on 10 fresh cadavers, the internal carotid artery (ICA) was the most important. Results Electromagnetic navigation helped to determine the course of important neurovascular. The ICA of the ventral skull base was divided into 5 segments+ 7 major branches, and the length and course of each were measured and recorded. Conclusion The identification and protection of ICA is the key to EEA treatment of ventral skull base lesions, and electromagnetic navigation assistance can improve the efficiency and safety of EEA surgery.

The reversal effect of albiflorin on multidrug resistance of human ovarian cancer and its mechanism / 中国药理学通报

Aim To study the reversal effect of albiflorin(AL)on multidrug resistance of human ovarian cancer and the potential mechanism. Methods The drug resistance reversal effect of AL on SKOV3/DDP cells was detected by CCK-8 kit,and the effect of AL on P-glycoprotein(P-gp)function was detected by flow cytometry. The effects of AL on MYC,WWP1 and ABCB1 in SKOV3/DDP cells were detected by RT-qPCR and Western blot. The MYC-knockdown SKOV3/DDP cell line was constructed by RNA interference technology,and its drug resistance,P-gp function and related gene and protein expression changes were investigated. Results AL had a drug resistance reversal effect on SKOV3/DDP cells and a concentration-dependent inhibitory effect on P-gp function. The inhibitory effects of AL 25,50 and 100 μmol·L-1 on ABCB1/P-gp,MYC and WWP1 were gradually enhanced. The inhibitory effect of MYCi975,a MYC inhibitor,on ABCB1/P-gp,MYC and WWP1 was stronger than or equivalent to that of AL 100 μmol·L-1 group. After knockdown of MYC in SKOV3/DDP cells,cell drug resistance,P-gp function,and related gene and protein expression were inhibited. Conclusions The drug resistance reversal effect of AL on SKOV3/DDP cells may be related to the inhibition of P-gp function and the expression of ABCB1/P-gp,MYC and WWP1,which provides an experiment base for the development of AL as a drug resistance reversal agent for the clinical treatment of ovarian cancer.

Mechanism study of OVA-induced allergic asthma in mice based on lipid metabolomics / 中国药理学通报

Aim To investigate the mechanism and search for potential biomarkers of ovalbumin ( OVA ) -induced asthma in mice base on lipidomics. Methods A BALB/c mouse model of asthma was prepared by OVA. TNF-α, IL-4, IL-10, IFN-γ levels in BALF and IgE level in serum were measured by ELISA. The inflammatory changes in mouse lung tissue were observed using HE staining. Lipid mediators ( LMs) in lung tissue and serum were quantified with UPLC-MS/ MS strategy. Results IgE level in serum and TNF-α, IFN-γ levels in BALF were higher (P <0.05) of asthmatic mice.Typical inflammatory manifestations were seen in lung tissue of asthmatic mice. A total of 57 lipid mediators were quantified with UPLC-MRM. LMs metabolic profiles differed significantly in serum and lung tissue between asthmatic and normal mice, 17 significantly different LMs were found in lung tissue and 6 LMs were found in serum, and the differential metabolites were produced through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 oxidase (P450) metabolic pathways. Conclusions OVA-induced allergic asthma can cause disorder of lip-id mediators, LMs and cytokines are involved in the occurrence and development of asthma. The differential LMs have potential research value as biomarkers for the development of allergic asthma.

Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet / 生理学报

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

Treadmill exercise alleviates neuropathic pain by regulating mitophagy of the anterior cingulate cortex in rats / 生理学报

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.

Diagnostic value of cross-primer isothermal amplification technology in tuberculosis and its related influencing factors / 中国热带医学

@#Abstract： Objective　To analyze the value and influencing factors of cross-primer isothermal amplification technology(CPA) in clinical screening and diagnosis of tuberculosis (TB). Methods　We collected 543 inpatients in the Second Affiliated Hospital of Hainan Medical College from January 1, 2018 to December 31, 2021, including 179 patients with tuberculosis, 187 patients with pneumonia and 177 patients with other diseases. The patients' sputum, alveolar lavage fluid, pleural effusion and midstream urine were detected by CPA, smear microscopy, culture method and gene detection. The value of CPA detection in the diagnosis of tuberculosis and its influencing factors were evaluated. Statistical analysis was performed using SPSS 26.0. Results　The total positive rate of CPA was 14.4% (78/543), and the positive rate of sputum samples accounted for 29.1% (39/134). Among the 78 cases of CPA positive patients, the tuberculosis group accounted for 69.2% (54/78), followed by pneumonia group 21.8% (17/78), and other diseases group accounted for 9.0% (7/78). Taking CPA test as the reference method, the "sensitivity" of smear microscopy was lower than that of genetic testing and culture, while the "specificity" was higher than that of culture and gene testing, and the "missed diagnosis rate" of smear microscopy was higher than that of genetic testing and culture. CPA test positive was related to gender, ESR and pneumonia. There is a good agreement between CPA test and culture method and gene test (Kappa>0.9), and a moderate agreement between CPA test and smear microscopy (Kappa=0.616). Conclusions　Sputum specimen is the best choice for CPA detection, while the value of pleural effusion detection is relatively limited. Sputum, alveolar lavage fluid and midcourse urine can be used as clinical specimens for screening and diagnosis of "tuberculosis group and other disease group", while sputum can be used for screening and diagnosis of "tuberculosis group and pneumonia group". Gender, ESR and pneumonia are the influencing factors of CPA positive patients. Therefore, CPA testing is worthy of clinical promotion, but more clinical research data are needed.

Research progress on the correlation between Helicobacter pylori and ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Helicobacter pylori is a common gram-negative bacterium, which is associated with a variety of gastroenteric diseases, such as gastritis, duodenal ulcer and gastric cancer. Recent studies suggested a potential role of Helicobacter pylori in the pathogenesis of common ocular diseases, such as central serous chorioretinopathy, glaucoma, anterior uveitis and ocular adnexal lymphoma. Helicobacter pylori might affect the pathophysiological process of ocular diseases through oxidative damage, circulatory disorders and immune injury. Some studies also suggested that eradication of Helicobacter pylori had certain effects on some ocular diseases. This review aims to summarize current evidence of the Helicobacter pylori in the pathogenesis of common ocular diseases, so as to encourage innovative approaches in the prevention and treatment of these ocular diseases.

Silenced ANP32A inhibits the growth, invasion and migration of colorectal cancer in vitro via the inactivation of AKT pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of ANP32A silencing on invasion and migration of colon cancer cells and the influence of the activity of AKT signaling pathway on this effect.@*METHODS@#Colorectal cancer HCT116 and SW480 were transfected with a small interfering RNA targeting ANP32A via a lentiviral vector. At 24, 48 and 72 h after the transfection, the changes in cell proliferation and AKT activity in the cells were detected using MTT assay and Western blotting, respectively. HCT116 and SW480 cells were treated with the AKT agonist SC79 or its inhibitor MK2206 for 24, 48, 72 and 96 h, and the changes in cell migration and invasion ability were analyzed using Transwell chamber assay and cell proliferation was assessed using MTT assay. The effects of SC79 and MK2206 on migration and invasion abilities of HCT116 and SW480 cells with or without ANP32A silencing were examined using wound healing and Transwell chamber assays, and the changes in the expression of metadherin (MTDH), a factor associated with cells invasion and migration, was detected with Western blotting.@*RESULTS@#Lentivirus-mediated ANP32A silencing significantly down-regulated the activity of AKT and inhibited the proliferation of both HCT116 and SW480 cells (P < 0.01). The application of AKT inhibitor MK2206 obviously inhibited the proliferation, invasion and migration of the colorectal cancer cells (P < 0.05), while the AKT agonist SC79 significantly promoted the invasion and migration of the cells (P < 0.01). In HCT116 and SW480 cells with ANP32A silencing, treatment with MK2206 strongly enhanced the inhibitory effects of ANP32A silencing on cell invasion and migration (P < 0.05) and the expression of MTDH, while SC79 partially reversed these inhibitory effects (P < 0.01).@*CONCLUSION@#ANP32A silencing inhibits invasion and migration of colorectal cancer cells possibly by inhibiting the activation of the AKT signaling pathway.

Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

Research Progress of High-intensity Interval Training in Cardiac Rehabilitation of Patients with Acute Coronary Syndrome / 中国医学科学院学报

Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.

Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy / 中华儿科杂志

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer / 中华妇产科杂志

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

Risk factors for hemorrhagic cystitis in children with β-thalassemia major after allogeneic hematopoietic stem cell transplantation / 中国当代儿科杂志

OBJECTIVES@#To explore the risk factors for hemorrhagic cystitis (HC) in children with β-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC.@*RESULTS@#Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05).@*CONCLUSIONS@#Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks / 法医学杂志

OBJECTIVES@#The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI.@*METHODS@#The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in.@*RESULTS@#Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid.@*CONCLUSIONS@#ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Analysis of clinical efficacy and risk factors of relapse in young patients with cervical instability treated by manipulation / 中国骨伤

OBJECTIVE@#To determine the clinical efficacy of different manipulation in the treatment of cervical instability in young people, and to analyze the risk factors of relapse of cervical instability in young people.@*METHODS@#From March 2021 to June 2022, the clinical data of 120 young patients with cervical instability were retrospectively analyzed. According to the different treatment methods, they were divided into rotation group (60 cases, 3 cases of loss) and tendon group (60 cases, 5 cases of loss). There were 25 males and 32 females in rotation-traction manipulation group;age ranged from 22 to 44 years old with a median of 28 years old;course of disease ranged from 0.17 to 120 months with amedian of 22 months. There were 22 males and 33 females in tendon-regulating manipulation group;age ranged from 21 to 42 years old with a median of 27 years old;course of disease ranged from 0.23 to 180 months with a median of 24 months. Both groups were treated for 2 weeks, once every other day for 7 times, and were followed up for 1 year. The clinical efficacy of the two groups was evaluated, and the visual analogue scale (VAS), neck disability index (NDI) were observed before and after treatment. One year after the course of treatment, patients with effective treatment were followed up to make statistics on recurrence. Patients with recurrence were included in the recurrence group, while those without recurrence were included in the non-recurrence group. Factors that may affect symptom recurrence were analyzed, and univariate and multivariate Logistic regression analysis were performed.@*RESULTS@#The 13 patients who failed the treatment (4 cases in the rotation-traction manipulation group and 9 cases in the tendon-regulating manipulation group) were not followed up. All the 99 patients who were effective in treatment were followed up ranged from 303 to 406 days with a median of 359 days. No complications occurred in all patients. There were significant differences in VAS and NDI between the two groups after treatment and before treatment (P<0.05), and there were significant differences in VAS and NDI between the two groups after treatment (P<0.05). Ninety-nine patients achieved follow-up, 56 (56.57%) relapsed and 43 (43.43%) did not. Univariate correlation analysis showed that NDI index, the time spent at the desk every day, the time spent using electronic products every day and angular displacement of anterior flexion before treatment in the relapse group were significantly higher than those in the non-relapse group (P<0.05). Logistic regression analysis showed that the time spent at the desk every day [OR=2.447, 95%CI(1.255, 4.771)], the time spent using electronic products every day [OR=1.892, 95%CI(1.066, 3.358)] and the angular displacement of anterior flexion of the cervical before treatment [OR=1.246, 95%CI(1.045, 1.485) ]were the risk factors for relapse.@*CONCLUSION@#Both rotation-traction manipulation and tendon-regulating manipulation can effectively treat cervical instability in young people, and rotation-traction manipulation has more advantages than tendon-regulating manipulation in improving cervical pain and cervical dysfunction in patients. The time spent at the desk every day, the time spent using electronic products every day, and the increase of cervical flexion angle displacement will increase the risk of relapse in patients.

Huangdi Anxiao Capsules-containing serum protects cell model from cognitive dysfunction in diabetes via inhibiting NLRP3-mediated pyroptosis / 中国中药杂志

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.