Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To explore the feasibility and safety of MCCE in gastrointestinal examination of elderly patients with malignant tumors.Methods Clinical data of 127 patients who underwent MCCE examination from April 2019 to September 2022 were retrospectively analyzed.According to age,the patients were divided into the elderly group(age≥65 year-old,n = 88)and the middle-aged group(40≤age<65 year-old,n = 39),and the clinical data of patients with malignant tumors were screened from the two groups for analysis and comparison.Results 131 patients received MCCE examination,and 4 elderly patients were excluded from this study due to swallowing failure,so 88 elderly patients were actually included in the study.In the elderly group,45.4%had serious cardiovascular diseases(40/88),27.3%had malignant tumors(24/88),8.0%had serious respiratory diseases(7/88),6.8%had anesthesia problems(6/88),and 9.1%had neurological diseases(8/88).Among the 24 elderly patients with malignant tumors,25.0%had severe cardiovascular disease,25.0%had poor general status,20.8%had brain metastases,and 12.5%had severe respiratory dysfunction.The positive diagnosis rate of gastric P2 lesions in the elderly group(52/88,59.1%)was significantly higher than that in the middle-aged group(13/39,33.3%)(P = 0.013).There was significant difference in positive rate of ulcer diagnosis between the two groups(29.5%and 10.2%)(P = 0.032).In patients with malignant tumors,the positive rate of ulcer diagnosis between the two groups(45.8%and 11.1%)was statistically significant(P = 0.038).The cleanliness and visualization scores of proximal stomach in the middle-aged group were higher than those in the elderly group,and the differences were statistically significant(P<0.05).Conclusion MCCE is generally effective and safe in elderly patients,especially those with malignant tumors,without missing any significant gastric lesions.

Ligand-gated ion channels transduce chemical signals into ionic currents while being bonded with specific ligands,thereby facilitating signal transduction and intercellular communication.These channels have become critical therapeutic targets for a variety of diseases.Ginsenosides,triter-penoid saponins primarily derived from herbs of the Panax genus,are known for their broad range of biological activities.Ginsenosides and their metabolites can regulate the functions of various ligand-gated ion channels,including nicotinic acetylcholine receptors,5-hydroxytryptamine type-3 receptors,γ-aminobu-tyric acid type-A receptors,glycine receptors,ionotropic glutamate receptors,ATP-gated P2X chan-nels,and transient receptor potential channels.They play important roles in anti-inflammation,analge-sics,immune regulation,anti-epilepsy,cognitive enhancement and neuroprotection.Further investiga-tion into the mechanisms by which ginsenosides regulate these channels will provide important evidence for their clinical applications and the development of new drugs.

Ligand-gated ion channels transduce chemical signals into ionic currents while being bonded with specific ligands,thereby facilitating signal transduction and intercellular communication.These channels have become critical therapeutic targets for a variety of diseases.Ginsenosides,triter-penoid saponins primarily derived from herbs of the Panax genus,are known for their broad range of biological activities.Ginsenosides and their metabolites can regulate the functions of various ligand-gated ion channels,including nicotinic acetylcholine receptors,5-hydroxytryptamine type-3 receptors,γ-aminobu-tyric acid type-A receptors,glycine receptors,ionotropic glutamate receptors,ATP-gated P2X chan-nels,and transient receptor potential channels.They play important roles in anti-inflammation,analge-sics,immune regulation,anti-epilepsy,cognitive enhancement and neuroprotection.Further investiga-tion into the mechanisms by which ginsenosides regulate these channels will provide important evidence for their clinical applications and the development of new drugs.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective To analyze the relationship between biochemical level and severity levels and clinical,duration of disease in patients with Parkinson Disease (PD).Methods 69 patients with PD and 69 healthy persons of similar sex and age were selected in the research.Serum uric acid and lipids levels were examined and compared.Results The serum uric acid,triglycerides,total cholesterol and low-density lipoprotein cholesterol (LDL-C) were (322.48 ± 66.18) μmol/L,(1.22 ± 0.86) mmol/L,(4.70 ± 0.92) mmol/L and (3.00 ± 0.85) mmol/L in control group,and (384.23 ± 88.28) μmol/L、(1.64 ± 0.94) mmol/L、(5.37 ± 1.31) mmol/L、(3.53 ± 1.03) mmol/L in control group.The differences are significant (t =-4.68,P =0.000;t =-2.74,P =0.007;t =-2.74,P =0.007;t =-3.49,P =0.001;t =-3.27,P =0.001).Serum UA concentration and high-density lipoprotein cholesterol (HDL-C),LDL-C were lower in patients with Parkinson's disease in duration of disease more than 3 years than those in duration of disease less than 3 years (t =3.373,P =0.001;t =2.440,P =0.017).The serum UA levels of any stages of PD patients were lower than the control group (P ＜ 0.05) according to Hoehn-Yahr staging.All lipid levels in early and middle stage PD disease patients were lower than those in control group (P ＜ 0.05).Serum UA,total cholesterol and HDL-C in female PD patients were (305.69 ± 54.25) μmol/L,(4.99 ± 0.95) mmol/L,(1.25 ± 0.27) mmol/L,and (339.76 ± 73.40) μmol/L,(4.41 ± 0.81) mmol/L,(1.06 ± 0.19) mmol/L in male patients.The difference is significant (t =2.198,P =0.031;t =-2.721,P =0.008;t =-3.266,P =0.002).Multivariate logistic regression models assessed lower uric acid concentrations is the risk of PD (OR =1.01,95％ CI 1.004 ～ 1.015,P =0.001).Conclusion Biochemical level changed differently in Parkinson disease and uric acid reduction could be a risk factor for PD.

Objective To explore the effect of intensive statin on platelet activity and inflammation factors 24 h after rat myocar‐dial infarction .Methods Seventy Sprague‐Dawley rats were randomly divided into five groups (n= 14):Sham‐operated group (SHAM group);AMI group(control group) ,general group;intensive statin therapy group ;general and intensive statin therapy group;established AMI rat model by ligation of left anterior descending branch of coronary artery .The general group ,general and intensive statin therapy group was fed atorvastatin by 10 mg · kg -1 · d-1 with distilled water 2 mL by intragastric gavage daily for two weeks .The intensive statin therapy group ,general and intensive statin therapy group was fed atorvastatin by 50 mg/kg with distilled water 2 mL by intragastric gavage 12 h before surgery .Serum PAC‐1 ,CD62p ,TNF‐α,hs‐CRP was measured at the time of 24 h of postoperation .Results TNF‐α,hs‐CRP ,PAC‐1 and CD62p levels in control group were significantly higher than the SHAM group and intensive statin group 24 h after the LADS were ligated(P<0 .05);and the factors of intensive statin group were signifi‐cantly lower than that of control group(P<0 .05) .There was no significant difference between the intensive statin group and gener‐al‐intensive group in the concentration of serum TNF ,hs‐CRP and the relative expression of PAC‐1 and CD62p(P> 0 .05);and there was no significant difference between normal group and control group in all the four factors (P>0 .05) .Conclusion Intensive statin therapy before acute myocardial infarction could decrease the level of inflammation factors and inhibit platelet activity postop‐eration .

Objective To improve the understanding of cutaneous intravascular natural killer/T-cell lymphoma (CIVNKTC). Methods Clinical data on five cases of CIVNKTC were collected. The histopathological feature, treatment and prognosis of CIVNKTC were retrospectively analyzed and discussed. Results Of the 5 patients, 1 was male and 4 were female. The age of onset ranged from 38 to 83 years (average, 56.2 years). All the patients presented with multiple plaques and nodules as the primary symptoms. Histopathological examination revealed vasodilatation in the dermis and subcutaneous tissue, as well as atypical lymphoid cells with large hyperchromatic nuclei containing 1-2 small nucleoli in dilated veins. Immunohistochemical studies of tumor cells showed positive staining for CD3ε, cytotoxic proteins (including T cell-restricted intracellular antigen-1, granzyme B and perforin)and Epstein-Barr virus(EBV)-encoded microRNA, but negative staining for cytokeratin, CD20, CD79a, CD4 and CD8. Furthermore, the tumor cells stained positive for CD56 in two patients. Among the 5 patients, only 2 received chemotherapy and the remaining received no treatment. During a 24-month follow-up, 4 patients died, and only 1 survived with the tumor. Conclusion CIVNKTC is a rare extranodal Hodgkin′s lymphoma with distinct histologic manifestations and immunophenotypes, rapid and aggressive clinical course, and poor prognosis.

Objective To investigate the effects of Shuxuetong Injection (SXT ) on expressions of cell apoptosis and TLR4 a-round ischemic area after focal cerebral infarction in rats and to discuss its neuroprotective mechanism on ischemia-induced brain in-jury .Methods The SD rats were subjected to establish the model of middle cerebral artery occlusion (MCAO)by nylon monofila-ment suture ,then were randomly divided into the sham-operated group ,the model group and the SXT treatment group ;the cell ap-optosis and the expressions of TLR4 mRNA and protein around ischemic area at 12 ,24 ,48 ,72 h after cerebral ischemia were detec-ted respectively by TUNEL test mediated with DNA ,RT-PCR and immunohistochemistry .Results In the model group ,the number of TUNEL positive cells ,the expressions of TLR4 mRNA and protein were gradually increased at 12 h ,reached the peak at 24 h , then decreased and were still higher than those in the sham-operated group(P<0 .01);in the SXT treatment group ,these expres-sions after 24 h were lower than those in the model group (P<0 .05)and declined as the treatment time increase(P<0 .05) .Conclu-sion In subacute stage of cerebral ischemia injury ,apoptosis is related with the expression of TLR4 ,SXT may inhibit apoptosis , down-regulate the expression of TLR4 around ischemic area ,this may be one of the mechanisms of neuroprotection .

Objective To observe the expression of angiotensin Ⅱ type 2 receptor (AT2R) and coronary arterial remodeling in ischemia-reperfusion(I-R) injury rat after the renin -angiotensin blocker valsartan pretreatment .Methods 123 rats were random-ly divided into 3 groups :sham -operation group(sham) ,control group and valsartan group(ARB) .The control group and the sham group received the gavage of normal saline and the ARB group received valsartan gavage 10 mg/(kg · d) for 4 weeks before surger-y .The I-R injury rat model was established by thoracotomy for ligating the left anterior descending (LAD) coronary artery and re-moving the ligation after 30 min .The sham group was performed the thoracotomy without ligation .At the 4 timepoints of postoper-ative 3 ,7 ,14 ,28 d ,the left ventricular diastolic and systolic pressures were measured ,then the rats were killed for collecting the rat heart sample .The section was stained by sirius red .The collagen deposition in coronary arterial remodeling and coronary arterial pe-ripheral area ,and the dynamic change of location and expression of AT2R in the coronary artery were observed by the immunohisto-chemical streptavidinbiotin peroxidase complex (SABC) .Results The immunohistochemical analysis revealed that AT 2R was local-ized in the adventitia of coronary arteries with the radial distribution ,showing the higher density especially in large coronary arterial peripheral area ,the partial expression existed in the coronary arterai intima .The expression of AT2R was transient ,which on 7 d af-ter I-R operation in the control group reached the peak value ,while the expression peak value of AT2R in the valsartan group was higher and earlier than that in the control group .The heart diastolic function on 3 d after I-R operation was impaired ;the left ven-tricular end diastolic presure (LVEDP) in the valsartan group was significantly lower than that in the control group .The collagen deposition of coronary peripheral mesenchyma on postoperative 28 d in the valsartan group was significantly lower than that in the control group;the coronary peripheral collagen deposition in the control group was gradually increased with the time progression , which on postoperative 14 ,28 d was significantly higher than that in the sham group .Conclusion Valsartan could inhibit the coronary arterial remodeling for protecting the heart function possible by the transient high AT 2R expression after myocardial I-R injury .