BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To investigate changes of choroid plexus volume in patients with essential hypertension using deep learning-based segmentation technique.Methods:According to the inclusion criteria,19 patients with essential hypertension who visited The 900th Hospital of People's Liberation Army Joint Service Support Force from December 2022 to May 2024 were divided into hypertension group.Additionally,19 healthy individuals,matched with the hypertension group in terms of gender,age,and years of education,were recruited as the healthy control group during the same period.All participants underwent data acquisition of three-dimensional T1(T1-3D)brain structural images using a Siemens 3.0T Trio magnetic resonance(MR)scanner.A pre-trained deep learning model,which based on the 3D U-Net architecture and generated by fully convolutional neural network,was employed for choroid plexus segmentation,and the total brain volume and lateral ventricle volume were calculated using the United Imaging Artificial Intelligence(AI)platform.Statistical analysis of the choroid plexus volume and other data for both groups were performed using SPSS27.0.Results:Compared with the healthy control group(1 866 mm3),the hypertensive group(2 047 mm3)showed an abnormal increase in choroid plexus volume(x2=3.900,P<0.05).Moreover,the choroid plexus volume was positively correlated with lateral ventricle volume and systolic blood pressure(r=0.849,P<0.05),and was negatively correlated with digit span(forward)in the hypertensive group(r=-0.374,P<0.05).Conclusion:The choroid plexus volume in patients with essential hypertension abnormally increased,which might be a factor promoting to changes in brain structure,it can affect further the cognitive function of patients with hypertension.

OBJECTIVE To explore the risk factors for serum COVID-19 antibodies in the population of Fuzhou to provide scientific basis for prevention and control strategies.METHODS The prospective study and the multi-stage stratified random sampling method were performed to select at least 200 subjects from each of the 12 counties(cit-ies)in Fuzhou.Questionnaires follow-ups and serum collections were conducted in Mar,Jun,Sep,and Dec.2024,respectively.The antibody levels in Dec.were divided into a high protective antibody group(IgG antibody≥50 AU/ml)and a low protective antibody group(IgG antibody≤20 AU/ml).The influencing factors of serum anti-body levels were analyzed by multivariate logistic regression model.RESULTS A total of 2816 subjects were en-rolled.In Mar,1454 subjects with high-protective antibodies were identified.After nine months of follow-up,of the 1454 subjects,344 had high protective antibodies and 369 had low protective antibodies in Dec..There were statistically significant differences in age,presence of typical symptoms after infection,underlying diseases,surgi-cal history,healing time,smoking and drinking histories between the high and low antibody groups(P<0.05).Multivariate logistic regression model showed that older age,underlying diseases,history of surgery,smoking and drinking were risk factors which could reduce antibody levels(P<0.05),while typical symptoms after infec-tion and longer recovery time were protective factors which could increase antibody levels(P<0.05).After the COVID-19 infection in spring of 2024,the serum antibody levels in Fuzhou residents showed the downward trend,especially after Sep.2024,with a more pronounced downward trend.CONCLUSIONS According to the risk factors of COVID-19 antibody levels,prevention and control efforts should be focused on the key population.It is necessa-ry to strengthen health education and carry out vaccination to maintain the levels of immunity to protect population from COVID-19 infection.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

OBJECTIVE To explore the risk factors for serum COVID-19 antibodies in the population of Fuzhou to provide scientific basis for prevention and control strategies.METHODS The prospective study and the multi-stage stratified random sampling method were performed to select at least 200 subjects from each of the 12 counties(cit-ies)in Fuzhou.Questionnaires follow-ups and serum collections were conducted in Mar,Jun,Sep,and Dec.2024,respectively.The antibody levels in Dec.were divided into a high protective antibody group(IgG antibody≥50 AU/ml)and a low protective antibody group(IgG antibody≤20 AU/ml).The influencing factors of serum anti-body levels were analyzed by multivariate logistic regression model.RESULTS A total of 2816 subjects were en-rolled.In Mar,1454 subjects with high-protective antibodies were identified.After nine months of follow-up,of the 1454 subjects,344 had high protective antibodies and 369 had low protective antibodies in Dec..There were statistically significant differences in age,presence of typical symptoms after infection,underlying diseases,surgi-cal history,healing time,smoking and drinking histories between the high and low antibody groups(P<0.05).Multivariate logistic regression model showed that older age,underlying diseases,history of surgery,smoking and drinking were risk factors which could reduce antibody levels(P<0.05),while typical symptoms after infec-tion and longer recovery time were protective factors which could increase antibody levels(P<0.05).After the COVID-19 infection in spring of 2024,the serum antibody levels in Fuzhou residents showed the downward trend,especially after Sep.2024,with a more pronounced downward trend.CONCLUSIONS According to the risk factors of COVID-19 antibody levels,prevention and control efforts should be focused on the key population.It is necessa-ry to strengthen health education and carry out vaccination to maintain the levels of immunity to protect population from COVID-19 infection.

Objective:To investigate changes of choroid plexus volume in patients with essential hypertension using deep learning-based segmentation technique.Methods:According to the inclusion criteria,19 patients with essential hypertension who visited The 900th Hospital of People's Liberation Army Joint Service Support Force from December 2022 to May 2024 were divided into hypertension group.Additionally,19 healthy individuals,matched with the hypertension group in terms of gender,age,and years of education,were recruited as the healthy control group during the same period.All participants underwent data acquisition of three-dimensional T1(T1-3D)brain structural images using a Siemens 3.0T Trio magnetic resonance(MR)scanner.A pre-trained deep learning model,which based on the 3D U-Net architecture and generated by fully convolutional neural network,was employed for choroid plexus segmentation,and the total brain volume and lateral ventricle volume were calculated using the United Imaging Artificial Intelligence(AI)platform.Statistical analysis of the choroid plexus volume and other data for both groups were performed using SPSS27.0.Results:Compared with the healthy control group(1 866 mm3),the hypertensive group(2 047 mm3)showed an abnormal increase in choroid plexus volume(x2=3.900,P<0.05).Moreover,the choroid plexus volume was positively correlated with lateral ventricle volume and systolic blood pressure(r=0.849,P<0.05),and was negatively correlated with digit span(forward)in the hypertensive group(r=-0.374,P<0.05).Conclusion:The choroid plexus volume in patients with essential hypertension abnormally increased,which might be a factor promoting to changes in brain structure,it can affect further the cognitive function of patients with hypertension.

OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy （DN） model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group， aminoguanidine group （positive control，100 mg/kg） and cornuside group （100 mg/kg）， and male C57BL/6J mice were included as normal group， with 6 mice in each group. Administration groups were given relevant medicine intragastrically， and normal group and model group were given a constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The levels of fasting blood glucose （FBG）， 24 h urinary protein， serum interleukin-12 （IL-12）， IL-10， blood urea nitrogen （BUN） and serum creatinine （Scr） were detected； the pathological injury， fibrotic change and glomerular microstructure of renal tissue were observed； the expressions of the receptor of advanced glycation end products （RAGE）， collagen type Ⅳ （COL-Ⅳ） and inducible nitric oxide synthase （iNOS） in renal cortex were detected in each group. RESULTS Compared with normal group， the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes； the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits； the levels of FBG and 24 h urinary protein， the serum levels of IL- 12， BUN and Scr， and the expression levels of RAGE， COL-Ⅳ and iNOS in the renal cortex were significantly increased， while the serum level of IL-10 was significantly decreased （P＜0.01）. Compared with the model group， the renal pathological injuries， fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly， and the above quantitative indexes were generally improved （P＜0.05 or P＜0.01）. CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response， reduce urinary protein excretion， and alleviate renal fibrosis， which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.

BACKGROUND:Due to the sudden release and the rapid removal by proteases,platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site.In recent years,researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE:To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS:The self-assembled polypeptide was synthesized by the solid-phase synthesis method,and the solution was prepared by D-PBS.Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions,so that the final mass fraction of polypeptides in the system was 0.1%,0.3%,and 0.5%,respectively.The hydrogel state was observed,and the release of growth factors in platelet-rich plasma was detected in vitro.The polypeptide self-assembly was stimulated by mixing 1%polypeptide solution with 1%human serum albumin solution,so that the final mass fraction of the polypeptide was 0.1%,0.3%,and 0.5%,respectively.The flow state of the liquid was observed,and the rheological mechanical properties of the self-assembled polypeptide were tested.The microstructure of polypeptide(mass fraction of 0.1%and 0.001%)-human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION:(1)Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma.Compared with platelet-rich plasma hydrogels,0.1%and 0.3%polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor,and extend the release time to 48 hours.(2)After the addition of human serum albumin,the 0.1%polypeptide group still exhibited a flowing liquid,the 0.3%polypeptide group was semi-liquid,and the 0.5%polypeptide group stimulated self-assembly to form hydrogel.It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides.With the increase of the mass fraction of the polypeptide,the higher the storage modulus of the self-assembled polypeptide,the easier it was to form glue.(3)Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin.After the addition of human serum albumin,the polypeptide nanofibers became significantly longer and cross-linked into bundles,forming a dense fiber network structure.Under a scanning electron microscope,the polypeptides displayed a disordered lamellar structure before adding human serum albumin.After the addition of human serum albumin,the polypeptides self-assembled into cross-linked and densely arranged porous structures.(4)In conclusion,the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide.This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma,which can be used as a new biomaterial for tissue repair.