The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

Objective To observe the efficacy of self-made auxiliary reduction device combined with sinus tarsi approach(STA)in the treatment of Sanders type Ⅱ to Ⅳ calcaneal fractures.Methods A total of 40 patients with Sanders type Ⅱ to Ⅳ calcaneal fractures admitted to our hospital from January to June 2023 were selected and divided into the control group and the observation group by the random number table method,with 20 cases in each group.Patients in the control group underwent surgical treatment with the heel extensile lateral approach(ELA),while patients in the observation group underwent surgical treatment with the auxiliary reduction device combined with STA.The surgical-related indicators,postoperative complications and ankle-foot anatomical indicators of patients in the two groups were compared.The recovery of limb function was evaluated by the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale and Maryland foot function score.Results There was no statistically significant difference in the operation time,postoperative incision drying time,or duration of postoperative pain between the two groups(P>0.05).The postoperative suture removal time of the patients in the observation group was shorter than that of the control group,and the difference was statistically significant(P<0.05).The incidence of skin edge necrosis of incision and the total incidence of complications of patients in the observation group were significantly lower than those in the control group(P<0.05).The B?hler angle and Gissane angle of patients in both groups increased after surgery compared with those before surgery(P<0.05);there was no statistically significant difference in the B?hler angle or Gissane angle after surgery of patients between the two groups(P>0.05).The AOFAS score1 week after surgery of the patients in the observation group was higher than that in the control group(P<0.05),while there were no statistically significant differences in the AOFAS scores or Maryland scores of patients at other time points between the two groups(P>0.05).Conclusion The use of the auxiliary reduction device in surgical treatment with STA for Sanders type Ⅱ to Ⅳ calcaneal fractures can effectively restore the function of the foot and ankle,with short postoperative suture removal time and low incidence of postoperative complications.

Objective To observe the efficacy of self-made auxiliary reduction device combined with sinus tarsi approach(STA)in the treatment of Sanders type Ⅱ to Ⅳ calcaneal fractures.Methods A total of 40 patients with Sanders type Ⅱ to Ⅳ calcaneal fractures admitted to our hospital from January to June 2023 were selected and divided into the control group and the observation group by the random number table method,with 20 cases in each group.Patients in the control group underwent surgical treatment with the heel extensile lateral approach(ELA),while patients in the observation group underwent surgical treatment with the auxiliary reduction device combined with STA.The surgical-related indicators,postoperative complications and ankle-foot anatomical indicators of patients in the two groups were compared.The recovery of limb function was evaluated by the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale and Maryland foot function score.Results There was no statistically significant difference in the operation time,postoperative incision drying time,or duration of postoperative pain between the two groups(P>0.05).The postoperative suture removal time of the patients in the observation group was shorter than that of the control group,and the difference was statistically significant(P<0.05).The incidence of skin edge necrosis of incision and the total incidence of complications of patients in the observation group were significantly lower than those in the control group(P<0.05).The B?hler angle and Gissane angle of patients in both groups increased after surgery compared with those before surgery(P<0.05);there was no statistically significant difference in the B?hler angle or Gissane angle after surgery of patients between the two groups(P>0.05).The AOFAS score1 week after surgery of the patients in the observation group was higher than that in the control group(P<0.05),while there were no statistically significant differences in the AOFAS scores or Maryland scores of patients at other time points between the two groups(P>0.05).Conclusion The use of the auxiliary reduction device in surgical treatment with STA for Sanders type Ⅱ to Ⅳ calcaneal fractures can effectively restore the function of the foot and ankle,with short postoperative suture removal time and low incidence of postoperative complications.

OBJECTIVE To evaluate the influence of gram-negative bacterial infection on the prognosis of patients with heart failure with reduced ejection fraction(HFrEF),and to explore its effects on biomarker dynamics,car-diac function recovery,rehospitalization rates and all-cause fatality rate.METHODS Clinical data were retrospec-tively collected from 100 patients diagnosed with HFrEF and combined with gram-negative bacterial infection at the Second Affiliated Hospital of Guizhou Medical University and the Cardiovascular Medicine of the Army Medi-cal Center of Chinese PLA from Jan.2022 to Jan.2024.Clinical baseline data,including demographic information,medical history and biomarkers[interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT),brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP)and troponin]were collected through follow-up visits for 12 months.Follow-up visits were conducted at discharge,3 months,6 months and 12 months,left ventricular ejection fraction(LVEF),NYHA classification(New York heart asso-ciation functional classification for heart),rehospitalization status and all-cause fatality rate were recorded.RESULTS Gram-negative bacterial infection significantly increased the rehospitalization and all-cause fatality rates in patients with HFrEF.The cumulative rehospitalization rate reached 45.00％within 12 months,and the all-cause fatality rate was 15.00％(P＜0.05).Inflammatory markers such as IL-6 and CRP were significantly ele-vated at baseline(P＜0.001)and decreased at discharge,while NT-proBNP levels were higher during the follow up period than those after the discharge,positively correlating with the numbers of rehospitalizations and fatality rates(r=0.752,P＜0.001).LVEF and NYHA classification improved in the short term but showed poor long-term prognosis.CONCLUSIONS Gram-negative bacterial infection significantly affects the long-term prognosis of patients with HFrEF,exacerbating cardiac function damage through inflammatory responses,thus increases re-hospitalization and fatality rates.This study provides new directions for clinical management,and emphasize the importance of early infection control.

OBJECTIVE To evaluate the influence of gram-negative bacterial infection on the prognosis of patients with heart failure with reduced ejection fraction(HFrEF),and to explore its effects on biomarker dynamics,car-diac function recovery,rehospitalization rates and all-cause fatality rate.METHODS Clinical data were retrospec-tively collected from 100 patients diagnosed with HFrEF and combined with gram-negative bacterial infection at the Second Affiliated Hospital of Guizhou Medical University and the Cardiovascular Medicine of the Army Medi-cal Center of Chinese PLA from Jan.2022 to Jan.2024.Clinical baseline data,including demographic information,medical history and biomarkers[interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT),brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP)and troponin]were collected through follow-up visits for 12 months.Follow-up visits were conducted at discharge,3 months,6 months and 12 months,left ventricular ejection fraction(LVEF),NYHA classification(New York heart asso-ciation functional classification for heart),rehospitalization status and all-cause fatality rate were recorded.RESULTS Gram-negative bacterial infection significantly increased the rehospitalization and all-cause fatality rates in patients with HFrEF.The cumulative rehospitalization rate reached 45.00％within 12 months,and the all-cause fatality rate was 15.00％(P＜0.05).Inflammatory markers such as IL-6 and CRP were significantly ele-vated at baseline(P＜0.001)and decreased at discharge,while NT-proBNP levels were higher during the follow up period than those after the discharge,positively correlating with the numbers of rehospitalizations and fatality rates(r=0.752,P＜0.001).LVEF and NYHA classification improved in the short term but showed poor long-term prognosis.CONCLUSIONS Gram-negative bacterial infection significantly affects the long-term prognosis of patients with HFrEF,exacerbating cardiac function damage through inflammatory responses,thus increases re-hospitalization and fatality rates.This study provides new directions for clinical management,and emphasize the importance of early infection control.

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

Objective: To investigate the reduction effect of hoding cricoarytenoid joint reduction with visual laryngoscope under intravenous anesthesia. Methods: The therapeutic effects of 40 patients with arytenoid dislocation(AD)treated by closed reduction in the single center from January 2020 to September 2021 were retrospectively analyzed, including 21 males and 19 females, median age 48 years. The etiology, symptoms, preoperative evaluation methods, reduction mode, reduction times, and the recovery of arytenoid cartilage movement and sound after reduction were evaluated and analyzed. Results: All patients had obvious hoarseness and breath sound before treatment. Under stroboscopic laryngoscope or electronic nasopharyngoscope, different degrees of vocal cord movement disorder and poor glottic closure can be seen. There were 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation. The etiology of dislocation of cricoarytenoid joint: 25 cases (62.5%) of tracheal intubation under general anesthesia were the most common causes, was as follows by laryngeal trauma, gastroscopy, cough, vomiting and so on. Among them, 28 cases of reduction were initially diagnosed in our department, and 12 cases were diagnosed later after failure of reduction treatment. Of the 40 patients, 6 underwent reduction 24 hours after dislocation; 18 cases from 3 days to 1 month; 7 cases from 1 to 3 months; 6 cases were reset in 3~6 months; Over 6 months in 3 cases. After one reduction, 10 cases (10/40, 25%) recovered normal pronunciation, 14 cases (14/40, 35%) recovered normal pronunciation after two reduction, 10 cases (10/40, 25%) recovered normal pronunciation after three times, 2 cases (2/40, 5%) recovered normal pronunciation after four times, and 1 case (2.5%) recovered normal pronunciation after five times. Thin slice CT scan of larynx and cricoarytenoid joint reconstruction showed the types of AD: subluxation in 37 cases (92.5%) and total dislocation in 3 cases; 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation; 29 cases (72.5%) had posterior dislocation and 11 cases (27.5%) had anterior dislocation. All patients were treated by intravenous anesthesia with arytenoid cartilage clamped by cricoarytenoid joint reduction forceps under visual laryngoscope. The curative effect was evaluated by stroboscopic laryngoscope and/or voice analysis at 1-2 weeks after operation. The vocal cord movement returned to normal and the pronunciation was good in 37 cases (92.5%). Conclusions: Hoding cricoarytenoid joint reduction with the vision laryngoscope under intravenous anesthesia is easy to operate and the reduction effect is more stable. It is a effective method for AD.
Anesthesia, Intravenous/adverse effects* ; Arytenoid Cartilage/injuries* ; Female ; Humans ; Intubation, Intratracheal/adverse effects* ; Joint Dislocations/therapy* ; Laryngeal Diseases/etiology* ; Laryngoscopes/adverse effects* ; Male ; Middle Aged ; Retrospective Studies

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

An auxiliary isolation device of cupping therapy for cross-infection prevention is designed to reduce the disinfection steps and be against cross transmission. This device is composed of a disposable isolation unit made of fire proof plastic material and a disposable cup-mouth fixator made of elastic material. The disposable isolation unit includes two parts, the cup neck isolation unit and the inner isolation unit of fire cup. These two parts connect with the disposable cup-mouth fixator. All of those three sections of the device are center-connected ring-like structure. This device can well prevent the direct contact of fire cup with the patient's skin surface, characterized as safety protection, simple operation and saving time and manpower.
Cupping Therapy ; Humans

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However, increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes, and endothelial cells within the brain parenchyma and the neurovascular unit.