Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.

Objective:To investigate the expression of NOD-like receptor protein 3(NLRP3)inflammasome and its relation-ship with granulosa cell apoptosis in patients with polycystic ovary syndrome(PCOS).Methods:Follicular fluid and ovarian granulosa cells were collected from 17 PCOS patients(PCOS group)and 20 non-PCOS patients(control group),and the expression levels of pro-inflammatory factor,TNF-α,IL-1β and IL-18 in follicular fluid were detected by ELISA.RT-PCR and Western blot were used to de-tect NLRP3 mRNA and NLRP3 inflammasome associated protein NLRP3,ASC and cleaved caspase-1 and autophagy related protein LC3-Ⅱ/LC3-Ⅰ and p62 expression level in granulosa cells.TUNEL assay was used to detect the apoptotic level of granulosa cells in both groups.NLRP3 silenced siRNA(si-NLRP3)and negative control sequence(si-NC)were transfected into human ovarian cancer granulosa cell line KGN cells by siRNA interference technique in vitro.TNF-α was used to simulate PCOS-related cell damage.KGN cells were divided into 4 groups according to different treatment methods:Ctrl group,TNF-α group,TNF-α+si-NLRP3 group and TNF-α+si-NC group.The levels of DHEA,testosterone,IL-1β and IL-18 in supernatant were detected by ELISA.TUNEL assay was used to detect the apoptosis level of KGN cells.The LC3-Ⅱ/LC3-Ⅰ and p62,NLRP3,ASC and cleaved caspase-1 protein expression levels,and NF-κB p-p65 level(NF-κB p-p65/NF-κB p65)in KGN cells were detected by Western blot.Results:Compared with con-trol group,the concentration of TNF-α,IL-1β,and IL-18 in follicular fluid of PCOS patients,and LC3-Ⅱ/LC3-Ⅰ,NLRP3 mRNA and the protein expression of NLRP3,ASC,and cleaved caspase-1 in granulosa cells of and apoptosis were significantly increased(P<0.05 or P<0.01),while the protein expression of p62 was significantly decreased(P<0.01).Compared with Ctrl group,the levels of DHEA,testosterone,IL-1β and IL-18 in supernatant of TNF-α group,TNF-α+si-NC group,and TNF-α+si-NLRP3 group,and LC3-Ⅱ/LC3-Ⅰ,ASC and cleaved caspase-1 protein expression,and the level of NF-κB p-p65 and apoptosis were significantly increased(P<0.05 or P<0.01),while p62 protein was significantly decreased(P<0.01).NLRP3 was significantly decreased except in TNF-α+si-NLRP3 group(P<0.01),while in the TNF-α group and TNF-α+si-NC group was significantly increased(P<0.01).However,com-pared with TNF-α group,the above indexes in TNF-α+si-NLRP3 group were significantly decreased(P<0.05),and TNF-α+si-NC group had no significant change(P>0.05).Conclusion:The over-activated NLRP3 inflammasome in granulosa cells may promote cell inflammatory injury and autophagy apoptosis in PCOS patients through NF-κB pathway.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.