Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Objective:The changes of serum inflammatory factors in patients with chronic obstructive pulmonary disease (COPD) with different traditional Chinese medicine (TCM) syndrome types were compared, and the characteristics and significance of inflammatory factors in COPD were discussed from the perspective of traditional Chinese and western medicine.Methods:A total of 100 patients with COPD who met the inclusion criteria and were admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to September 2022 were selected and divided into phlegm turbation obstructing lung group ( n=50) and lung and kidney qi deficiency group ( n=50) according to TCM syndrome types. Twenty healthy subjects in the same period were selected as control group. Serum levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and other inflammatory factors were compared in each group. Results:The MCP-1, IL-6, ESR, CRP, white blood cell count (WBC) and procalcitonin (PCT) of COPD patients in phlegm turbation obstructing lung group were significantly higher than those in lung and kidney qi deficiency group (all P<0.05). The WBC, MCP-1, MIP-1α, IL-6, ESR and CRP of COPD patients in the lung and kidney qi deficiency group were significantly higher than those in the control group (all P<0.05). In the phlegm turbation obstructing lung group, the MIP-1α, MCP-1, IL-6, ESR, CRP, WBC, and PCT were significantly higher than those in the control group (all P<0.05). Conclusions:Patients with COPD have inflammatory reactions, and the inflammatory reactions of patients with phlegm turbation obstructing lung syndrome are more obvious than those with lung and kidney qi deficiency syndrome. The inflammatory factors MCP-1, MIP-1α, IL-6, ESR, CRP, WBC, PCT and other indicators could be used to judge the degree of COPD inflammation, which had certain clinical guiding significance for different syndrome types of COPD patients.

Objective: To study the bone regeneration capacity of the BMSCs cell sheets combined with PRP used with dental implant. Methods: BMSCs were isolated from young SD rats and induced to form cell sheets(BMSCs); PRP were prepared from the fresh blood of rats; PRP gel with BMSCs fragments(BMSCs + PRP) were injected into the space of dental implant of Ti and β-TCP. BMSCs, PRP and BMSCs + PRP with the implant were respectively transplanted into nude mice(n = 6). 8 weeks after transplantation bone regeneration were examined by Micro CT and hard tissue slicing. Results: The group of BMSCs + PRP showed more new bone formation around implants with blood vessel than the group of BMSCs and PRP. Conclusion: BMSCs sheets with PRP can improve the bone regeneration around dental implants.

Objective: To investigate the pharmacodynamics of modified Xiaochaihutang granules (MXG) and its active ingredients group (AIG) on gastric ulcer in order to provide scientific basis for the clinical effect and lay foundation for the development of related hospital preparations.Methods: Gastric ulcer models induced by pyloric ligation,acetic acid and ethanol were applied to observe the curative effects of MXG and its AIG, and the effects of MXG and its AIG on gastric secretion, gastric acid content, pepsin activity, superoxide dismutase (SOD) and malondialdehyde(MDA) contents were also studied.Results: Compared to the model control group,MXG and AIG could significantly reduce the ulcer index(P<0.01), total acidity(P<0.01),and pepsin activity (P<0.05 or 0.01), increase the SOD activity (P<0.05)and inhibit the increase of lipid peroxide MDA.Conclusion: MXG and AIG show better control effects on acute and chronic gastric ulcer, and the effects are related to reducing the activity of pepsin, increasing the SOD activity, inhibiting the increase of lipid peroxide MDA and so on.

Objective To investigate the clinical efficacy of intraoperative methylprednisolone used in combination with perioperative enteral nutrition support in improving liver synthetic function after hepatectomy and postoperative recovery.Methods In this prospective controlled trial,79 patients treated with hepatectomy at Departement of Hepatobiliary Pancreatic Surgery in Drum Tower Hospital between June 2013 and May 2014 were included and divided into control group (n =39) and steroid group (n =40) according to the order of surgery.The control group underwent hepatectomy only,while the steroid group received intraoperative methylprednisolone (500 mg) at the start of liver excision.Both of the two groups were given the same perioperative enteral nutrition support.Liver function,prealbumin (PA),and C-reactive protein (CRP) levels were measured before and on days 1,3,and 5 after the operation.Human blood albumin infusion volume,postoperative gas passing,postoperative hospital stay,and incidence of complications were recorded.Results The serum level of PA on day 3 after hepatectomy was significantly higher in the steroid group than in the control group [(101.26 ±61.17) mg/L vs.(81.84 ±43.58) mg/L,t =-1.607,P =0.049].The serum level of cholinesterase on day 1 after hepatectomy was significantly higher in the steroid group than in the control group [(5.60±1.54) kU/Lvs.(4.68±1.01) kU/L,t=-3.136,P=0.004].On day1 and day 3 after hepatectomy,the serum levels of CRP were significantly lower in the steroid group than in the control group [(41.79 ±20.86) mg/L vs.(62.08 ±38.33) mg/L,t =2.933,P=0.027;(64.14 ±32.38) mg/L vs.(102.64 ± 49.05) mg/L,t =4.127,P =0.006].The postoperative hospital stay was significantly shorter in the steroid group than in the control group [(12.62 ±5.74) d vs.(15.41 ± 10.00)d,t =1.514,P =0.002].Conclusion Intraoperative use of methylprednisolone combined with perioperative enteral nutrition support may inhibit postoperative inflammatory response,promote early recovery of liver synthetic function,and help to promote rehabilitation after hepatectomy.

Objective To explore the value of a set of combined vascular anastomosed flap.Methods The 36 cases were injured,the site of injury in knee and leg or ankle and foot,upper limb.Skin defect with bone and joint,tendon exposure.Selection of anastomosis of blood vessel with large flap,wherein the subscapular vascular anastomosis scapular-lateral thoracic flap in 7 cases,the maximum was 70 cm × 10 cm; anastomosis of subscapular artery lateral thoracic-latissimus dorsi muscle flap in 9 cases,the maximum was 42 cm× 24 cm.Anastomosis of subscapular artery of the scapular-back the latissimus dorsi muscle flap in 2 cases; anastomotic lateral circumflex femoral vessels with lateral femoral cutaneous nerve thigh anterior medial-tensor fascia latae flap in 8 cases; anastomosis of anterior tibial artery and the superficial peroneal nerve in the anterior ankle-dorsal foot flap in 5 cases; anastomosis of dorsal vessels and superficial peroneal nerve of the extensor digitorum brevis muscle-dorsal foot joint flap in 5 cases.Results Following up 8 months to 25 years,twenty-three cases were 19 years.All flaps survived and all the wounds were covered,infection were cured,the skin have aesthesia,fracture healing.Five cases were performed muscle tendon and arthrosis solution for creating conditions for the functional recovery of limb.Conclusion Anastomosis of blood vessel anastomosis combined flap can replace multiple vascular flaps combination,saving,convenient,high success rate,widen the indications.

Objective To observe effect of intra-and post-operative mild hypothermia using an ice blanket on patients with severe traumatic brain injury (sTBI).Methods Twenty sTBI patients with Glasgow Coma Scale (GCS) of 3-8 points were included and were assigned to either ice bag cooling (Bag group) or ice blanket cooling (Blanket group) (n =10 each) according to random number table.Patients in Bag group had temperature reduction by placing ice bag over great vessels,whereas in Blanket group an ice blanket (temperature was set as the nasopharyngeal temperature of 33℃-34℃) was employed to have temperature reduction.Hypothermia therapy in the two group groups was initiated from the beginning of operation and continued for 48 hours after operation.Intracranial pressure,cerebral perfusion pressure (CPP) and GCS in both groups were recorded respectively at 10 minutes before operation (T0) and at 8,12,24,48 and 72 hours after operation (T1,T2,T3,T4 and T5).Venous blood of the two groups was harvested to assay the serum concentration of neuronspecific enolase (NSE),myelin basic protein (MBP)and S-100β at T0,T3,T4,-Ts and at 96 hours after operation (T6) by ELISA method.Glasgow Outcome Scale (GOS) was evaluated at postoperative six months.Results In Bag group,body temperature (T1-T5) of the patients had no significant decrease (P ＞ 0.05) and NSE (T3-T6),S-100β (T3-T6) and MBP (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared with those in T0 ; intracranial pressure (T2-T5) was increased (P ＜ 0.05) and CPP (T3-T5) was lowered (P ＜ 0.05) when compared with those in T1.In Blanket group,body temperature (T1-T6) of the patients presented was decreased significantly (P ＜ 0.01) and NSE (T3-T6),MBP (T5-T6) and S-100β (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared those in T0 ; intracranial pressure (T2-T6) was increased (P ＜ 0.05) and CPP had no significant changes (P ＞0.05) when compared with those in T1.By contrast with those in the same time points in Bag group,lower body temperature (T1-T5) (P ＜ 0.001),lower intracranial pressure (T2-T5),higher CPP (T3-T5) as well as lower NSE (T4-T6),MBP (T4-T6) and S-100β(T6)were observed in Blanket group (P ＜0.05 or 0.01).Changes of GCS and GOS in the two groups were no significance (P ＞0.05).Conclusion Intraoperative and postoperative mild hypothermia therapy using an ice blanket may alleviate the degree of brain injury in sTBI patients.