Chronic heart failure （CHF） is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons， resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease， hypertension and pulmonary heart disease recur frequently and persist for a long time， presenting blood stasis in meridians and collaterals， stagnation of water and dampness， and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders， oxidative stress responses， myocardial cell apoptosis， autophagy， inflammatory responses， etc. According to the theory of restraining hyperactivity to acquire harmony， we believe that under normal circumstances， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway functions normally， maintaining human physiological activities and energy metabolism. Under pathological conditions， the AMPK signaling pathway is abnormal， causing energy metabolism disorders， inflammatory responses， and myocardial fibrosis. Traditional Chinese medicine （TCM） can regulate the AMPK signaling pathway through multiple mechanisms， targets， and effects， effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM， our research group， through literature review， summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients， TCM compound prescriptions， and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

Objective:To investigate the occurrence and managements of poor recovery after total endoscopic middle ear surgery. Methods:A total of 302 cases（315 ears） who underwent endoscopic middle ear surgery in our hospital from June 2020 to June 2021 were collected. Follow up by means of endoscopy, pure tone hearing threshold, tympanogram was conducted at 1 month, 3 months, 6 months and 1 year after surgery to analyze the incidence, possible causes, treatment strategies and effects of poor results tympanic membrane healing and hearing recovery. Results:Among 302 patients（315 ears） followed up, there were 28 cases with poor recovery. There were fourteen cases of poor eardrum healing, of which 10 cases achieved healing of eardrum after tympanic membrane patching in the outpatient department, with a success rate of about 71.4%. TM recurrence adhesion occurred in 4 cases after surgeries of cholesteatoma and adhesive otitis media. One case completely recovered after self eustachian tube insufflation, while 2 cases maintained the degree of eardrum subsidence, and one ineffective patient chose resurgical treatment, with an effective rate was 75.0%. Failure in hearing improvement occurred in 8 cases, all of which underwent second surgical exploration, and seven cases were improved after the second surgery, with an effective rate of 87.5%. Among the 8 patients with no improvement or aggravation of hearing loss after surgery, four cases had postoperative B-type or C-type of tympanogram, and the hearing could not improve after self eustachian tube insufflation for secondary surgical exploration. and the hearing improved after the secondary surgery. Incorrect orientation of ossicular prosthesis was accounted for another 2 cases, the hearing was improved after the ossicular orientation adjustment. One patient with lateral healing of TM and failed hearing recovery was corrected by a second operation. One case of tympanosclerosis underwent stapes release surgery, but hearing recovery still failed. One patient had recurrent postoperative cicatricial atresia of external auditory canal, and the patient was reluctant to undergo reoperation. Postoperative delayed facial paralysis occurred in 1 case, and the facial paralysis recovered recovered after conservative treatments. Conclusion:Eardrum patch and eustachian tube autoflation are simple and effective early outpatient treatment for patient with poor recovery. For those who failed with conservative treatments such as eardrum patch or eustachian tube and poor hearing recovery, the second surgical exploration is safe and effective. Regular follow up after endoscopic middle ear surgery is necessary for the managements of poor recovery.
Humans ; Ear, Middle/surgery* ; Female ; Male ; Endoscopy/methods* ; Adult ; Middle Aged ; Tympanic Membrane/surgery* ; Treatment Outcome ; Hearing Loss/surgery* ; Otologic Surgical Procedures/methods* ; Otitis Media/surgery* ; Eustachian Tube/surgery*

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

  Objective  To explore the effect of esketamine on working memory impairment in neuropathic mice and its underlying mechanism.  Methods  Fifty clean grade male C57BL/6J mice (2 months) were divided into 5 groups by random number table method: sham+saline (SN group), CCI+saline (CN group), CCI+esketamine(CE group), CCI+ANA-12 (CA group), CCI+ANA-12+esketamine (CAE group), with 10 mice in each group. Chronic constriction injury (CCI) was employed to establish a neuropathic pain model. On the 16th day after modeling, CE group and CAE group were administered ketamine (10 mg/kg), CAE group received ANA-12 (0.5 mg/kg) half an hour before ketamine injection, CA group was only given ANA-12, and SN group and CN group received an equivalent volume of saline. The administration was done through intraperitoneal injection for 5 consecutive days. The open-field test (OFT), paw withdrawal threshold (PWT), paw withdrawal latency (PWL) and Y-maze test were performed from day 21 after surgery. Bromo-2-deoxyUridine (BrdU) was dissolved in saline and intraperitoneally injected into the mice on days 21 to 23 after the surgery. Western blot was performed to determine the expression of Brain-derived neurotrophic factor(BDNF) in hippocampus, the immunofluorescence was performed to determine the number of BrdU and doublecortxin (DCX) positive cells in the dentate gyrus (DG) area of hippocampal.  Results  Compared with SN group, the other four groups showed significant reductions in both PWT and PWL on day 21 after surgery (all P<0.05); There was no significant difference in the total distance travelled by the 5 groups of mice (P=0.142); In the Y maze test, compared to SN group, the accurate percentage of spontaneous alternation in CN group showed significant reductions (P<0.001), which was reversed by esketamine administration (P<0.001); compared with CE group, there was a significant reduction of the accurate percentage of spontaneous alternation in CAE group (P=0.004). The expression of BDNF protein in CN group was lower than that in SN group (P=0.021) and CE group (P=0.030), and compared with CE group, the expression of BDNF was significant decreased in CEA group (P=0.043). The number of BrdU positive and DCX positive cells significantly reduced in the DG area of the hippocampus in CN group compared to SN group (P=0.025) and CE group (P=0.003). The number of BrdU positive and DCX positive cells in CAE group significantly reduced in the DG region of the hippocampus compared to CE group (P=0.014).  Conclusion  Esketamine maybe improve working memory impairment in neuropathic mice and the neurogenesis in dentate gyrus area of hippocampal through the BDNF-TrkB pathway.

With the development of biotechnology,research on liquid biopsy of tumor has been deepened.As one of the major methods of liquid biopsy,circulating tumor DNA(ctDNA)has attracted much attention due to its non-invasive,safe and early detection of lesions.At present,studies have shown that ctDNA has certain potential in the early diagnosis and grading of bladder cancer,selection and efficacy analysis of targeted therapy,and recurrence and progression of tumors.This paper reviews the characteristics of ctDNA,research progress,detection methods and its clinical value in the diagnosis,treatment and prognosis of bladder cancer.In recent years,the development of ctDNA detection technology has made many advances and attempts in the development of sequencing and mutation detection technologies and in enhancing its ability as a biological marker for cancer detection.Detection of ctDNA in plasma samples can help achieve accurate classification in the diagnosis of early-stage bladder cancer,but requires the support of more advanced detection technologies due to low levels.Targeted sequencing-based ctDNA analysis is a promising method for predicting disease recurrence and aggressiveness in NMIBC patients.In patients with advanced bladder cancer,ctDNA can be used to collect the characteristics of mutation types to guide medication,adjust treatment and monitor prognosis.Although there are still challenges of ctDNA in the application of bladder cancer,it has shown a wide range of application prospects.

OBJECTIVE This study aimed to investigate the effects of Buyang Huanwu Decoction(BYHWD)on delaying vascu-lar aging and explore whether the underlying mechanism is associated with microRNA-665(miR-665)/DNA damage-regulated autoph-agy modulator1(DRAM1)-mediated autophagy.METHODS Male SD rats with natural aging were randomly divided into the aging group,BYHWD low,medium,high dosage groups(9.25,18.5,37.0 g·kg-1)and resveratrol group(80 mg·kg-1),with a young group set as well.The rats in each group were dissected and the blood vessels were collected.ELISA was used to assess senescence as-sociated β-galactosidase(SA-β-Gal)activity and advanced glycation end products(AGEs)level in vascular tissues.HE,Masson,and EVG staining were performed to observe the morphological structure of the vascular tissues.The qPCR was performed to detect the expression of miR-665 in vascular tissues.Bioinformatics analysis and dual-luciferase reporter gene experiments were used to validate the targeting relationship between miR-665 and DRAM1.Transmission electron microscope was used to observe the autophagosome.Western blot was performed to determine the protein expression of p16,DRAM1 and autophagy-related proteins Bec-lin1,p62 and LC3.Immunohistochemistry was used to detect the protein expression of DRAM1 in vascular tissues.RESULTS Com-pared to the young group,the aging group showed increased SA-β-Gal activity,AGEs level and p16 protein expression(P<0.01),disordered arrangement of vascular tissues,thickened media,increased collagen fibers,fractured and disorganized elastic fibers.The expression of miR-665 was upregulated(P<0.01).The number of autophagosomes was reduced.The protein expression of Beclin1 and LC3Ⅱ/Ⅰ downregulated(P<0.01),while the protein expression of p62 was upregulated(P<0.01).In addition,the protein ex-pression of DRAM1 was downregulated in vascular tissues(P<0.01).Compared to the aging group,intervention with BYHWD and resveratrol reduced SA-β-Gal activity(P<0.01),AGEs level and p16 protein expression(P<0.05,P<0.01),improved vascular morphology and elastic fiber structure,reduced collagen fibers.High dose BYHWD significantly downregulated miR-665 expression(P<0.01),increased the number of autophagosomes.Different doses of BYHWD significantly upregulated protein expression of Bec-lin1(P<0.05,P<0.01),medium and high doses of BYHWD significantly upregulated protein expression of LC3Ⅱ/Ⅰ(P<0.01),and downregulated protein expression of p62(P<0.01).High dose BYHWD significantly upregulated protein expression of DRAM1 in vascular tissues of aging rats(P<0.05).Bioinformatics analysis revealed the presence of specific complementary binding sites between the sequences of miR-665 and DRAM1.Dual-luciferase reporter assays confirmed that miR-665 targeted DRAM1 gene and negatively regulated DRAM1 protein expression.CONCLUSION BYHWD may promote the protein expression of DRAM1 by inhibiting the ex-pression of miR-665,thereby promoting vascular autophagy and delaying vascular aging.