BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCsExo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood.This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCsExo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess b-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry.Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.

[摘 要] 目的：系统评价基于PD-1/PD-L1抑制剂的免疫联合治疗（以下称“免疫联合治疗”）对比舒尼替尼治疗晚期肾细胞癌（RCC）的安全性和有效性。方法：检索PubMed、Embase、Cochrane Library及中国知网（CNKI）数据库，收集国内外公开发表的免疫联合治疗对比舒尼替尼应用于晚期RCC的随机对照试验（RCT），检索时间均为自建库时间至2022年10月。由两名研究者独立评价纳入研究的质量、提取资料并交叉核对，采用StataMP16.0软件进行Meta分析。结果：共纳入6项RCT，Meta分析结果显示，（1）有效性：与舒尼替尼相比，免疫联合治疗显著提高了晚期RCC患者的总生存期[OS，HR=0.74，95% CI （0.67，0.80），P<0.01]和无进展生存期[PFS，HR=0.66，95% CI （0.51，0.81），P<0.01]；（2）安全性：两治疗组均有较高的不良反应（AE）发生率，差异无统计学意义。但免疫联合治疗组发生皮肤及内分泌系统AE显著高于舒尼替尼治疗组，而血液系统相关AE则明显低于舒尼替尼治疗组；（3）以1%为临界点，免疫联合治疗组的RCC患者，无论是PD-L1阳性或阴性的，其OS和PFS均高于舒尼替尼组。结论：免疫联合治疗可显著延长晚期RCC患者的OS和PFS，但不同系统发生AE有差异，且RCC患者PD-L1表达状态（1%为临界点）并不影响免疫联合治疗的获益。

Objective:To evaluate the effects of the cassette 14C-urea breath test kit, scintillation sampling bottle (solid-state scintillation method) and liquid scintillation 14C-urea breath test kit in the diagnosis of Helicobacter pylori ( H. pylori) infection. Methods:From January 7 to October 28, 2020, 239 patients were enrolled who visited Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine and the First Affiliated Hospital of Nanchang University. All subjects first received 14C-urea breath test.Within >1 to <7 days after gas collection, mucosal tissues were taken under gastroscopy for gold standard test, including biopsy and rapid urease test (RUT). If both biopsy and RUT indicated H. pylori positive, the result of gold standard test was H. pylori positive, and if both were negative, the result of gold standard test was H. pylori negative. If the results of biopsy and RUT were inconsistent, they were not included in the subsequent analysis. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were analyzed. The safety of the test was evaluated by whether there were any adverse events during the test. Descriptive methods were used for statistical analysis. Results:Among the 239 subjects, 12 cases did not complete the test, 227 subjects finally completed the test. The test completion rate was 95.0% (227/239). No.008 patient was only included in the analysis of cassette 14C-urea breath test kit and scintillation sampling bottle because of lacking the result of liquid scintillation breath test. The results of gold standard test showed that among 227 patients, 87 cases were H. pylori positive, 118 cases were H. pylori negative. The results of biopsy and RUT were inconsistent in 22 cases, so they were not included in the subsequent analysis. Excluding No.008 patient, the results of gold standard test showed that 86 cases were H. pylori positive and 118 cases were negative. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of cassette 14C-urea breath test kit, scintillation sampling bottle, and the liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were 91.9%, 100.0%, 96.6%, 100.0% and 94.4%, respectively; 95.4%, 97.5%, 96.6%, 96.5% and 96.6%, respectively; and 96.5%, 99.2%, 98.0%, 98.8% and 97.5%, respectively. Only one adverse event (right upper abdominal pain after eating) occurred. Combined with the patients condition, the adverse event was determined as the onset of chronic cholecystitis and it might not be related to the test medication. Conclusions:Cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit have reliable performance, good safety, and high sensitivity, specificity and accuracy in the diagnosis of H. pylori infection, which are worthy of clinical application.

Objective To investigate the clinical effect of facial dermabrasion by microcrystal combined with red blue light in the treatment of acne pitting scar.Methods Selected from June 2013 to April 2016 hospital dermatology outpatients,98 cases of facial acne pitting scar were retrospectively analyzed,in which 50 cases of patients with facial acne dermabrasion were treated with red and blue light treatment (combined group),48 patients only choose facial acne dermabrasion treatment (control group),then treatment effect was compared between the two groups.Results At 3 months after operation,the ECCA score and mean sag depth of the two groups were significantly lower than those of the preoperative (t=23.208 and 18.586,P＜0.001).The ECCA score of the combined group was significantly lower than that of the control group (t=7.039,P＜0.05);The healing rate was 80％,which was significantly higher than those in the control group (56.25％) (x2 =6.387,P＜0.05);after 1 months and 3 months;the subjective satisfaction scores of the patients in the combined group were significantly higher than those in the control group (t=3.318 and 3.776,P＜0.05);Patients in the combined group were significantly earlier than the control group (t =4.419,P＜0.05);the incidence of edema and erythema was significantly lower in the combined group than in the control group (x2 =5.096,P＜0.05).Conclusions Facial acne dermabrasion by microcrystal combined with red and blue light treatment is superior to the single use of dermabrasion.

Objective To analyze the expression and clinical significance of PIK 3CA protein in squamous cell carcinoma of the esophagus .Methods Forty -five samples of surgical resection of esophageal squamous cell carcinoma were collected as the observation group ,and 45 normal tissues adjacent to the carcinoma were selected as the control group.The expression of PIK3CA protein in the tissues of esophageal squamous cell carcinoma and the corresponding para cancerous tissue was detected by immunohistochemistry ( IHC).Results The results of IHC showed that the positive expression rate of PIK 3CA protein in esophageal squamous cell carcinoma was 53.33%, which in adjacent normal tissues was 0.00%,the difference was statistically significant (χ2 =32.727,P<0.01).The positive expression rate of PIK3CA protein was correlated with lymph node metastasis ,differentiation and clinical stage of esophageal squamous cell carcinoma (χ2 =5.180,8.201,13.566,P=0.023,0.017,0.001),and was not correlated with the degree of tumor invasion (χ2 =0.952,P =0.329).Conclusion The expression of PIK3CA protein is abnormal in esophageal squamous cell carcinoma ,and the expression of PIK3CA protein plays a role in the occurrence and development of esophageal squamous cell carcinoma .

Objective To investigate the clinical value of endoscopic ultrasonography (EUS)on minute gas-tric stromal tumor (MGST).Methods 90 patients diagnosed with MGST were randomly divided into two groups. 45 patients in A group were given conventional endoscopic diagnosis,45 cases in B group were treated with endoscopic ultrasound diagnosis.After the two groups of patients with endoscopic treatment,the coincidence rate of preoperative diagnosis and pathological inspection test results was recorded,clinical features in MGST under EUS diagnosis were analyzed.Results All patients were diagnosed in the case of endoscopic surgery,endoscopic submucosal dissection (ESD)accounted for 94.44%,which was significantly higher than the use of endoscopic full -thickness resection (EFR)percentage of 5.56%,and the difference was statistically significant (χ2 =14.22,P <0.05);The two groups of patients after endoscopic treatment,were diagnosed as pathological inspection MGST.Preoperative diagnosis showed that EUS MGST suspected cases of 40 patients,conventional endoscopy MGST suspected cases of 31 cases.The diag-nosis coincidence rate of B group (88.89%)was significantly higher than that in A group (68.88%),the difference was statistically significant (χ2 =5.40,P <0.05);MGST of EUS images could be clearly observed in patients with tumor morphology,size,location,growth pattern,internal parenchyma,echo pattern,strengthening methods,the compo-sition ratio in line with the results of endoscopic treatment,diagnosis results in line with the pathological diagnosis. Conclusion EUS has significant value for the diagnosis of MGST,it has advantages in the clinical guidance and treatment.

[ ABSTRACT] AIM: To explore the relationship between FRAS 1 protein and brain metastases of non-small cell lung cancer (NSCLC).METHODS:The mRNA expression of FRAS1 in the brain metastatic tumor tissues and primary tumor tissues of NSCLC was detected by qPCR .The protein expression of FRAS 1 in the tumor tissues and normal tissues adjacent to tumor tissues of NSCLC was measured by SP method of immunohistochemistry .The protein expression of FRAS 1 in NSCLC primary tumor tissues with or without brain metastases was also determined .RESULTS:The mRNA expression of FRAS1 in the brain metastatic zone was nearly 10 times higher than that in the primary tumor tissues , and there was sig-nificant difference between the 2 groups (P<0.05).FRAS1 protein was expressed in the NSCLC primary tumor tissues , but was not found in the normal tissues adjacent to primary tumor tissues .The protein expression of FRAS 1 in the NSCLC with brain metastases was significantly higher than that without brain metastases ( P<0.01 ) .CONCLUSION: FRAS1 protein may be associated with the occurrence of NSCLC .The over-expression of FRAS1 protein may be related to brain metastases with NSCLC .

BACKGROUND:Peripheral facial nerve injury first involves the retrograde reactions of central nervous system axons, and nerve regeneration wil depend on the survival and functional status of neuronal cel bodies. OBJECTIVE:To explore the expression of neuronal cadherin and placental cadherin in facial nuclei after facial nerve injury. METHODS:New Zealand white rabbits were randomly divided into model group (n=48) and control group (n=8). In the model group, every eight rabbits were used to carry out the test respectively at 1, 4, 7, 14, 21 days after the model of facial nerve injury (right side) was established. SP and real-time quantitative PCR methods were taken to test the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus at mRNA and RESULTS AND CONCLUSION:The control group had neuronal cadherin-and placental cadherin-positive neurons. In the model group, neuronal cadherin and placental cadherin positively expressed in the facial motorneurons (right side), and their expressions were peaked at 14 days. Compared with the control group, the mRNA expression of neuronal cadherin in the facial motorneurons was increased significantly at 4-28 days after injury;the mRNA expression of placental cadherin in the facial motorneurons was decreased significantly at 1 day after injury, and then increased significantly at 7-28 days. It is suggested that the expression of neuronal cadherin and placental cadherin is positive in the early stage of facial nerve injury, and the expression of placental cadherin is always present, while the expression of neuronal cadherin relatively lasts for a short time. After facial nerve injury, the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus is both increased, which indicates that the facial nerve regeneration may be related to the high expression of adhesion molecules.

OBJECTIVE: To explore the clinical repair value of facial skin and tissue defect caused by tumour, trauma and infection with the axial flap. METHOD: The clinical data of 38 patients with facial skin and tissue defect were analyzed retrospectively. All of them were repaired by the axial flap. RESULT: The axial flap was alive in all patients, and all incision healed in the first stage. All patients had a satisfied result after the second stage of flap surgery. CONCLUSION The method of the axial flap in face can be clinically applied in the facial skin and tissue defects caused by tumour, trauma injury and infection. Because the axial flap cotained named blood vessel, the survival rate of it is high.
Dermatologic Surgical Procedures ; Face ; surgery ; Humans ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Surgical Flaps ; Wound Healing

OBJECTIVETo analyze the relationship between the ictal onset zone and dominant interictal epileptiform foci in tuberous sclerosis complex (TSC) patients.

METHODClinical data of 20 patients with TSC which had epileptic seizures during Video-EEG monitoring was assessed. Consistency and dominance of focal interictal epileptiform activity and the ictal onset zone were identified. Concordance between interictal and ictal findings was analyzed.

RESULTOf the 20 patients, 7 were female, and 13 were male. The age of epilepsy onset was from 15 d to 6 years. The Video-EEG monitoring age was from 6 months to 11 years. Family history was found in three cases. Abnormality in neuroimaging existed in 17 of 18 patients who were examined. Interictal EEG showed hypsarrhythmia in 3 patients, multifocal epileptiform activity with a dominant focus in 12 patients, both focal and generalized discharges in 2 patients, and only focal discharges in 3 patients. The seizures types during EEG monitoring included epileptic spasms, partial seizure, atypical absence, and generalized or focal myoclonic seizure. The most common seizure type was partial seizure and then epileptic spasms. EEG in 4 patients with epileptic spasms showed ictal generalized discharges and interictal hypsarrhythmia or generalized discharges. Clinical manifestation of epileptic spasms was asymmetric in 3 patients. Lateralization and location of interictal and ictal discharges were consistent in 2 of the 3 patients, while only lateralization consistency in 1 of the 3 patients. Partial seizures as the only seizure type were monitored in 13 patients. Of the 13 patients, lateralization and location of interictal and ictal discharges were inconsistent in 2 patients (15%), consistent in 8 patients (62%), lateralization or location consistent in 2 patients (15%). One case could not be analyzed because of uncertainty of lateralization and location of seizure onset.

CONCLUSIONIn the majority of patients with TSC, multifocal interictal epileptiform activity is present, in which a most dominance of focal epileptiform activity could be found. For some epileptic seizures or the majority of partial seizures, the ictal onset zone is concordant with the dominance of focal interictal epileptiform foci. The concordance might have positioning reference significance for preoperative evaluation of epilepsy surgery.

Brain ; pathology ; physiopathology ; Brain Mapping ; methods ; Cerebral Cortex ; pathology ; physiopathology ; Child ; Child, Preschool ; Electroencephalography ; statistics & numerical data ; Epilepsies, Partial ; diagnosis ; etiology ; physiopathology ; Female ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Predictive Value of Tests ; Retrospective Studies ; Seizures ; diagnosis ; etiology ; physiopathology ; Tuberous Sclerosis ; complications ; diagnosis ; physiopathology