OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

This article reports a case of primary Müllerian adenosarcoma(MA)of the ovary admitted to the Obstetrics and Gynecology Hospital,Fudan University in 2022,reviews the literature on this rare disease,and shares the experience of its diagnosis and treatment.The patient was a 29-year-old unmarried woman who underwent laparoscopic resection of an ovarian lesion in another hospital.Intraoperatively,it was observed that"the right ovary was enlarged with a cauliflower-shaped mass at the lower pole,measuring about 11 cm×8 cm,unencapsulated,with a fish-like texture,which was completely excised and sent for examination."Postoperative consultation with a(tertiary)hospital in Beijing and our pathology department suggested the diagnosis of ovarian adenosarcoma.Therefore,we performed a comprehensive staged surgery for the patient,i.e.,laparoscopic right salpingo-oophorectomy,cystectomy of the left ovary,omentectomy,multiple peritoneal biopsies,and hysteroscopic resection of cervical canal lesions.The patient received four cycles of postoperative chemotherapy with paclitaxel and ifosfamide.After chemotherapy,the patient has been regular followed up and showed no signs of recurrence during the almost 2-year postoperative follow-up period.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.
Animals ; Rats ; Rats, Sprague-Dawley ; Beclin-1 ; Mitochondria ; Cerebral Infarction ; Protein Kinases

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.
Humans ; Antibodies/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Squamous Cell/surgery* ; Cisplatin ; Esophageal Neoplasms/surgery* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Programmed Cell Death 1 Receptor/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective: Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. Methods: We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Results: Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Conclusion Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

This study observed the effects of ethanol extract of Gastrodiae Rhizoma(GE) on multiple aspects of mitochondrial dysfunction by investigating the mitochondria isolated from rat brains subjected to focal middle cerebral artery occlusion/reperfusion(MCAO/R). SD rats were randomly divided into a sham operation group(Sham), a model group(MCAO/R), low-and high-dose ethanol extract of GE groups(262.3 and 524.6 mg·kg~(-1)), and a nimodipine group(Nim, 15 mg·kg~(-1)). After continuous intragastric administration for 7 days, the MCAO/R model was induced in rats by the suture method. The neurological function and percentage of cerebral infarction volume were measured 24 h after reperfusion, and mitochondrial ultrastructure was observed under an electron microscope. Mitochondria were separated by gradient centrifugation and detected for reactive oxygen species(ROS), malondialdehyde(MDA), respiratory chain enzyme complex Ⅰ-Ⅳ activity, mitochondrial permeability transition pore(mPTP), mitochondrial membrane potential(MMP), and mitochondrial adenosine triphosphate(ATP) content. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression of cytochrome C(Cyt C) in different sites. TUNEL staining was used to observe the apoptosis of brain tissues in each group, and Western blot was used to detect the expression of B-cell lymphoma 2(Bcl-2) and Bcl-2-associated X protein(Bax) in brain tissues. The experimental results revealed that compared with the Sham group, the MCAO/R group showed evident neurological dysfunction and cerebral infarction(P<0.01) accompanied by mitochondrial swelling and crest disappearance, increased ROS level and MDA content, inhibited activity of respiratory chain enzyme complex Ⅰ-Ⅳ, abnormal opening of mPTP, and reduced MMP and mitochondrial ATP(P<0.01). Besides, many Cyt C was released from mitochondria into the cytoplasm to induce apoptosis(P<0.01). The ethanol extract of GE positively affected the behavior deficit and mitochondrial health of MCAO/R rats, with the manifestations of decreased production of ROS and MDA(P<0.01), potentiated activity of mitochondrial respiratory chain enzyme complex Ⅰ-Ⅳ, and restored the level of mPTP(P<0.05). In addition, the ethanol extract of GE reduced the loss of MMP and the escape of Cyt C to the cytoplasm(P<0.05), reduced the number of TUNEL positive cells(P<0.01) accompanied by the decrease in Bax and the up-regulation of Bcl-2(P<0.01), and increased the level of ATP(P<0.01). In conclusion, GE ethanol extract has a protective effect against MCAO/R-induced mitochondrial dysfunction, and the mechanism may be related to the regulation of oxidative stress, maintenance of functional morphology of mitochondria, and inhibition of endogenous apoptosis.
Animals ; Rats ; bcl-2-Associated X Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Ethanol ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology* ; Neuroprotective Agents/pharmacology* ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Infarction, Middle Cerebral Artery ; Mitochondria ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Cytochromes c/metabolism* ; Adenosine Triphosphate/pharmacology*

OBJECTIVE: To investigate the changes of gene sequencing and proteomics of apheresis platelet (AP) exosomes in different storage periods and predict the function of AP exosomes in different storage periods. METHODS: Platelets at different storage periods of 0 day (D0), 3 day (D3) and 5 day (D5) were collected, exosomes were extracted with Gradient centrifugation; gene sequencing and proteomic analysis were used to analyze the exosomes, and biological functions of platelet exosomes were analyzed and predicted by bioinformatics. Liquid mass spectrometry (LMS) was used to detect the changes and function prediction of exosomes proteins. The small RNA sequencing library was prepared, and the constructed library was sequenced and bioinformatics technology was used for data analysis. RESULTS: AP exosome iTRAQ protein analysis showed that AP exosomes stored in D3 with 55 up-regulated proteins and 94 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2), while AP exosomes stored in D5 with 292 up-regulated proteins and 53 down-regulated proteins (P<0.05, FC<0.83 or FC>1.2) as compared with D0. KEGG pathway analysis showed that the proteins were mainly involved in transport and metabolism, immune system, cancer, membrane transport and other processes. There were statistically significant differences between AP exosome miRNAs in different storage days (P<0.01). The number of miRNA up-regulated and down-regulated was 374 and 255 as compared with the number of platelet exosomes miRNA stored in D3 and D0, while that was 297 and 242 in D5 and D0, and 252 and 327 in D5 and D3, respectively. The target genes of differential platelet exosome miRNAs were analyzed by GO enrichment. Target genes of differential miRNA were mainly involved in membrane composition, mainly played molecular functions binding to proteins, and participated in biological processes of transcriptional regulation. CONCLUSION The exosome differential proteins and miRNAs in D5 are significantly different from those in the D0 of APs, and they are involved in various biological processes.
Blood Component Removal ; Blood Platelets/metabolism* ; Exosomes/metabolism* ; Humans ; MicroRNAs/genetics* ; Proteomics

Objective:To explore the predictive value of peripheral perfusion index (PI) combined with central venous-arterial carbon dioxide tension to arterial-venous oxygen content ratio(Pv-aCO 2/Ca-vO 2)for prognosis after initial resuscitation of septic shock. Methods:A total of 76 cases of patients with septic shock from January 2019 to January 2021 in emergency intensive care unit (EICU) of Harrson international peace hospital affiliated to Hebei Medical University were enrolled. All recovered according to 2016 Severe Sepsis and Septic Shock Treatment International Guidelines 2016 (SSC 2016) , and PI was monitored, central vein and arterial blood gas analysis was performed, and the ratio of Pv-aCO 2/Ca-vO 2 was calculated.The PI and Pv-aCO 2/Ca-vO 2 at 3 h,hemodynamic variables,oxygen metabolism indexes,APACHEⅡ and SOFA score were recorded.Patients were divided into survival group and death group according to 28 d survival condition, the dfferences in demographics and clinical data were compared between two groups.The Kaplan-Meier urviving curve was created and the survival of the patients was analyzed by the Log-rank test. Risk factors associated with the prognosis were analyzed using the Cox regression analysis. The role of PI and Pv-aCO 2/Ca-vO 2 in prediting death was evaluated by receiver operating characteristic curves(ROC). Results:There were 37 cases in survival group and 39 cases in death group.Compared with death group, PI in survival group [(1.77±0.63) vs. (0.89±0.69)]was significantly higher,and Pv-aCO 2/Ca-vO 2[(1.52±0.52) vs. (2.57±0.86)] was significantly lower ( P<0.05). Kaplan-Meier survival curve showed that the median survival time in the high PI group [20.09 d (95% CI:16.95-23.24) vs.11.00d (95% CI:7.14-14.86)] was longer than that in the low PI group(χ 2=12.424, P=0.000),and that in low Pv-aCO 2/Ca-vO 2 group [23.74 d (95% CI:20.35-27.13) vs.12.85d (95% CI:9.75-15.95)] was longer than that in the high Pv-aCO 2/Ca-vO 2 group (χ 2=12.200, P=0.000) .Cox regression analysis showed that both PI ( RR=0.397, 95% CI: 0.230-0.687, P =0.001) and Pv-aCO 2/Ca-vO 2 ( RR=1.878, 95% CI: 1.169-3.019, P =0.009) were predictors of 28 d mortality.The area under the ROC curve of PI and Pv-aCO 2/Ca-vO 2 for predicting 28 d death in patients with septic shock were 0.828 (95% CI: 0.732-0.923) and 0.785 (95% CI: 0.6777-0.893)respectively. The optimal cutoff values were 0.52 (sensitivity 58.3% and specificity 94.4%) and 0.35 (sensitivity 88.9% and specificity 63.9%)respectively, and the AUC of the combined prediction of the two indicators was 0.903 (95% CI: 0.835-0.971). Conclusions:Combination of PI and Pv-aCO 2/Ca-vO 2 is better to predict the risk of adverse outcomes of septie shock patients,and may provide useful information for the resuscitation at early stage.