Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:Cellular senescence is closely related to the development and progression of osteoarthritis,but the specific targets and regulatory mechanisms are not yet clear. OBJECTIVE:To mine key genes in cellular senescence-mediated osteoarthritis by integrating bioinformatics and machine learning approaches and validate them via experiments to explore the role of cellular senescence in osteoarthritis. METHODS:The osteoarthritis gene expression profiles obtained from the GEO database were intersected with cellular senescence-related genes obtained from the CellAge database and the expression of the intersected genes was extracted for differential analysis,followed by GO and KEGG analysis of the differential genes.The key osteoarthritis cellular senescence genes were then screened by protein-protein interaction network analysis and machine learning,and in vitro cellular experiments were performed.Finally,the expression of the key genes was detected by qPCR. RESULTS AND CONCLUSION:A total of 31 osteoarthritis cell senescence differential genes were identified.GO analysis showed that these genes were mainly involved in the biological processes,such as regulation of leukocyte differentiation,monocyte differentiation,regulation of T cell differentiation and exerted roles in DNA transcription factor binding,histone deacetylase binding,chromatin DNA binding,and chemokine binding.KEGG analysis showed that osteoarthritis cell senescence differential genes were mainly activated in the JAK/STAT signaling pathway,PI3K/Akt signaling pathway and FoxO signaling pathway.MYC,a key gene for osteoarthritis cellular senescence,was identified by protein-protein interaction network topology analysis and machine learning methods.The results of the in vitro cellular assay showed that the mRNA expression of MYC was significantly lower in the experimental group(osteoarthritis group)than the control group(normal group)(P＜0.05).To conclude,MYC can be a key gene in the senescence of osteoarthritic cells and may be a new target in the prevention and treatment of osteoarthritis by mediating immune response,inflammatory response and transcriptional regulation.

Coronary artery bypass grafting (CABG) is one of the most effective revascularization treatments for coronary heart disease. Secondary prevention strategies, which rely on antiplatelet and lipid-lowering drugs, are crucial after CABG to ensure the durability of revascularization treatment effects and prevent adverse cardiovascular and cerebrovascular events in the medium to long term. Previous research conducted by Professor Zhao Qiang's team from Ruijin Hospital of Shanghai Jiao Tong University, known as the DACAB study, indicated that dual antiplatelet therapy (DAPT, specifically ticagrelor+aspirin) after CABG can enhance venous graft patency. However, it remains uncertain whether DAPT can further improve the medium to long-term clinical outcomes of CABG patients. Recently, the team reported the medium to long-term follow-up results of the DACAB study, termed the DACAB-FE study, finding that DAPT administered after CABG can reduce the incidence of major cardiovascular events over five years and improve patients' medium to long-term clinical outcomes. This article will interpret the methodological highlights and significant clinical implications of the DACAB-FE study.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in patients with type 2 diabetic retinopathy(T2DR)and to explore the correlation of TCM syndromes with serum inflammatory factors and adiponectin(APN)levels,so as to provide evidence for TCM syndrome differentiation of T2DR.Methods A cross-sectional case-control study was conducted in 42 patients(involving 84 eyes)diagnosed as T2DR in the Department of Ophthalmology,Ganzhou People's Hospital from September 2022 to March 2023.The correlation between fundus fluorescein angiography(FFA)staging and TCM syndrome differentiation in patients with T2DR was explored.The relationship between TCM syndrome types and serum levels of inflammatory factors and APN,as well as the differences in serum inflammatory factors and APN levels of the patients with various FFA stages were analyzed.The correlation between each variable and TCM syndrome types in patients with T2DR was investigated.Results(1)Among the 42 patients with T2DR,27 cases were male and 15 cases were female,and their age averaged(54.0±12.0)years old.Among them,14 cases(33.3％)were differentiated as liver-kidney deficiency with malnutrition of eye collateral syndrome,15 cases(35.7％)were differentiated as yin-essence deficiency with internal dry-heat syndrome,9 cases(21.4％)were differentiated as qi-yin deficiency with collateral stasis and obstruction syndrome,4 cases(9.5％)were differentiated as yin-yang deficiency with blood stasis and phlegm coagulation syndrome,and none case(0.0％)was differentiated as spleen dysfunction and water-damp obstruction syndrome.(2)FFA staging showed that FFA staging ≥ 4[i.e.,having proliferative diabetic retinopathy(PDR)]was found in 78.6％(11/14)of the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome,73.3％(11/15)of the patients with yin-essence deficiency with internal dry-heat syndrome,100％(9/9)of the patients with qi-yin deficiency with collateral stasis and obstruction syndrome,and 100％(4/4)of the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome.But the intergroup comparison showed no significant differences among various syndrome types(P=0.272).(3)Among the 42 patients with T2DR,35 patients(83.3％)had higher level of tumor necrosis factor-α(TNF-α),28 patients(68.3％)had higher level of C-reactive protein(CRP)and 38 patients(90.5％)had higher level of glycosylated hemoglobin(HbA1c)than the normal.However,there was no significant difference in the levels of serum inflammatory factors of TNF-α,CRP,interleukin-6(IL-6)and vascular endothelial growth factor(VEGF),APN and HbA1c among the patients with different FFA stages(P＞0.05),neither did the difference in serum APN,TNF-α,CRP,IL-6 and VEGF levels among the patients with different TCM syndrome types(P＞0.05).(4)The correlation analysis showed that the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome had a shorter course of eye diseases than the patients with liver-kidney deficiency with malnutrition of eye collaterals syndrome(r=-0.467,P=0.051),had higher CRP level than the patients with yin-essence deficiency with internal dry-heat syndrome(r=0.592,P=0.010),and had higher CRP level(r=0.668,P=0.013)and a longer course of diabetes(r=0.629,P=0.021)than the patients with qi-yin deficiency with collateral stasis and obstruction syndrome.Conclusion Increased serum TNF-α and CRP expressions are presented in the patients with T2DR.Liver-kidney deficiency with malnutrition of eye collaterals syndrome and yin-essence deficiency with internal dry-heat syndrome are the common syndromes in T2DR.Yin-yang deficiency with blood stasis and phlegm coagulation syndrome is closely correlated with CRP level,and the patients with yin-yang deficiency with blood stasis and phlegm coagulation syndrome have a longer course of diabetes.

Objective To verify the therapeutic effect of platelet lysate(PL)on spinal cord injury in rats.Methods Thirty male SD rats were randomly divided into the sham operation group,the injury group and the treatment group,with 10 rats in each group.Rats in the sham operation group did not smash the spinal cord after exposure;rats in the injury group were established the rat spinal cord injury model by smashing the spinal cord with a 20 g of self-made smashing machine weights from a height of 5 cm for 5 seconds after exposure;rats in the treatment group were given intraperitoneal injection of 2 mL of PL once a day for 19 days after established the spinal cord injury model.The hind limb function was evaluated by Basso Beattie Bresnahan(BBB)score and slope experiment;six rats were randomly selected from each group,and the spinal cords of the rats were taken on the 7th day after surgery for HE staining and electron microscopy scanning to observe their pathological changes.Results There were statistically significant differences in BBB scores on the 3rd,7th and 14th days after surgery among the three groups(P<0.05),and the BBB scores of the treatment group were higher than those of the injury group(P<0.05).There were statistically significant differences in the results of slope experiment on the 7th and 14th days after surgery between the treatment group and the injury group(P<0.01).HE staining showed that the neuronal degeneration and necrosis decreased,the cell swelling improved and the microglial phagocytosis decreased in the treatment group compared with those in the injury group.The results of electron microscopy showed that the astrocyte cytoplasmic swelling and local cell membrane damage were alleviated,and the mitochondrial swelling and degeneration in the treatment group were relieved compared with those in the injury group.Conclusion PL can improve the hind limb function and reduce the pathological changes after spinal cord injury in rats,which has therapeutic effect on spinal cord injury in rats.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Interleukin-8 ; Interleukin-10 ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; I-kappa B Kinase ; Spleen ; Irbesartan ; Uridine Triphosphate ; Yang Deficiency/drug therapy* ; Kidney/pathology*

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

OBJECTIVE: To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism. METHODS: Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 μg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 μg/l IL-6 and 75 μg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot. RESULTS: The cell proliferation rate of 25, 50, 75 and 100 μg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r_{24 h}=-0.990, r_{48 h}= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 μg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in 25, 50 and 75 μg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 μg/ml kaempferol group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05). CONCLUSION Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-6/metabolism* ; Kaempferols/pharmacology* ; Signal Transduction ; Apoptosis ; Janus Kinase 2 ; Cell Proliferation ; Leukemia, Myeloid, Acute