ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

OBJECTIVE To prepare hyaluronic acid （HA）-modified emodin （EMD）-contained multi-walled carbon nanotubes （MWCNTs） drug delivery system （HA-MWCNTs-EMD） and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD； subsequently， the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference， the drug release in vitro of the above two drug delivery systems was investigated； the uptake of EMD by two breast cancer cells （MCF-7， MDA-MB-231 cells） was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 （CD44）， activity， apoptosis and lactate dehydrogenase （LDH） release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both （63.52±2.74）%， with drug loading rates of （25.01±1.83）% and （12.13± 1.96）%， particle sizes of （865.95±2.16） and （351.86±1.68） nm， polydispersity indexes of 0.54±0.02 and 0.23±0.01， and Zeta potentials of （23.87±0.14） and （－42.79±0.39） mV， respectively. The 2， 4， 6， 8， 10， 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD， while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD （P＜0.05）； the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD （P＜0.05）. Compared with the free EMD group， the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release， significantly lower surface CD44 expression （except for the MWCNTs-EMD group） and cell viability in both cell types， and the effect of HA-MWCNTs-EMD was more pronounced （P＜0.05）. CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully； the drug delivery system has a certain slow-release effect， which can significantly reduce the activity of breast cancer cells， promote their apoptosis and increase the release of LDH， and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.

ObjectiveTo evaluate the efficacy and safety of Lianhua Qingke tablets in the treatment of acute bronchitis in children with the syndrome of phlegm-heat obstructing lung. MethodA randomized， open， parallel controlled， and multi-center clinical study was conduted. Children with acute bronchitis （syndrome of phlegm-heat obstructing lung） were randomly assigned to an observation group and a control group. The control group received routine basic treatment， and the observation group was treated with Lianhua Qingke Tablets on the basis of routine basic treatment. After 7 days of treatment， the clinical efficacy， TCM efficacy， time to symptom disappearance， time to cough disappearance， and clinical safety were compared between the two groups. ResultA total of 248 children were included （124 in the observation group and 124 in the control group）. After 7 days of treatment， the total response rate in terms of clinical efficacy in the observation group was 96.8% （120/124）， which was higher than that （90.3%， 112/124） in the control group （Z=-5.034， P<0.01）. The total response rate in terms of TCM syndrome in the observation group was 97.6% （121/124）， which was higher than that （93.5%， 116/124） in the control group （χ²=-5.326， P<0.01）. The scores of physical signs and TCM symptoms in the observation group were lower than those in the control group at the time of taking medicine for 3 days and 7 days （P<0.01）. The time to symptom disappearance and the time to cough disappearance in the observation group were shorter than those in the control group （P<0.01）. Drug-related adverse reactions occurred in neither group. ConclusionLianhua Qingke tablets demonstrate a definite effect on acute bronchitis in children with the syndrome of phlegm-heat blocking lung. The tablets can significantly shorten the course of disease and relieve cough and TCM symptoms， with high safety， which is worthy of clinical application and promotion.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.

Objective:To analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Objective To analyze the effects of different anastomotic methods on flap survival rate and wound healing factors of patients with transplantation of superficial branch perforator flap of superficial circumflex iliac artery(SCIA).Methods A total of 100 patients with skin defects of limbs admitted to our hospital from January 2019 to August 2022 were selected and divided into end-to-end anastomosis group(56 cases)and end-to-side anastomosis group(44 cases)according to different anastomosis methods.In the end-to-end anastomosis group,the end of the flap artery was anastomosed with the end of the aortic branch in the affected area.In the end-to-side anastomosis group,the end of recipient flap artery was anastomosed with the side of aorta.Patients in both groups were followed up for 6 to 12 months,the arterial caliber,lateral caliber and anastomosis time were compared between the two groups.The survival of the flap,the occurrence of venous crisis,the shape and function of the flap and donor area were observed.Results There was no statistically significant difference in the arterial caliber or lateral caliber of patients between the two groups(P>0.05).The anastomosis time of patients in the end-to-end anastomosis group was significantly shorter than that in the end-to-side anastomosis group(P<0.05).All 56 cases in the end-to-end anastomosis group survived.In the end-to-side anastomosis group,venous crisis occurred in 4 cases,with venous thrombosis,2 cases survived after re-anastomosis,2 cases were changed to abdominal pedicled flap when venous crisis occurred again,the appearance and function of the flap and donor area were satisfactory 6 months to 1 year after surgery(P<0.05).There was no significant difference in color,thickness,vascular distribution or flexibility of donor area of patients between the two groups(P>0.05).There was no significant difference in pain,appearance,vitality and recreation of recipient area of patients between the two groups(P>0.05).Conclusion The application of different arterial anastomosis methods in the transplantation of superficial branch perforator flap of SCIA for the treatment of skin and soft tissue defects of limbs is safe and reliable,the postoperative survival of the flap is good,the healing is not affected by the anastomosis method,and the appearance of the affected area is satisfactory,which is worthy of clinical promotion.

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P < 0.001) from baseline to week 24. A total of 18 CHB patients completed 48 weeks of follow-up. The complete virological response rate after 48 weeks of treatment was higher than that at baseline (94.4% vs 77.8%, χ 2 =2.22, P =0.34), and there were significant increases in IBil ( t =2.43, P =0.03), TBA ( Z =-2.24, P =0.03), and bone mineral density T score of lumbar vertebra ( t =2.92, P = 0.01) and femoral neck ( t =2.42, P =0.03) and a significant reduction in liver stiffness measurement ( t =-2.31, P =0.03). There were no significant changes in β2-MG, URBP, and α1-MG after treatment (all P > 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

OBJECTIVE: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. METHODS: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. RESULTS: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). CONCLUSION For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.
Humans ; Fracture Fixation, Intramedullary ; Bone Nails ; Traction ; Blood Loss, Surgical/prevention & control* ; Retrospective Studies ; Treatment Outcome ; Femoral Fractures ; Hip Fractures/surgery* ; Lower Extremity ; Surgical Wound ; Fracture Fixation, Internal