BACKGROUND:It has been found that internal factors such as anatomical structure,hormone level and neuromuscular function of athletes are closely related to the risk of anterior cruciate ligament injuries,and external factors such as the material of the playing field also become one of the risk factors affecting the occurrence of non-contact anterior cruciate ligament injuries,but they are relatively under-attended in the current studies. OBJECTIVE:To explore effects of artificial turf versus natural grass on the biomechanical performance of the lower limbs in young females during jump-landing. METHODS:According to the test needs,artificial turf and natural grass in accordance with the standards of GB/T 20033.3-2006 and GB/T 19995.1-2005 were leveled and fixed on two three-dimensional force measuring platforms.Twenty-one young females were voluntarily recruited and completed the jump-landing task on the artificial turf and natural grass.Subjects stood on the steps and then jumped forward,jumped down to the force measuring platform and immediately jumped with full force to the force measuring platform again.The two landings were required to fall to the two force measuring platforms,and the whole jumping action was considered successful without any pause.The kinematic,kinetic and electromyographic data of the lower limbs during the landing process were collected synchronously to compare and analyze the differences between the two. RESULTS AND CONCLUSION:In terms of kinetics,posterior and vertical ground reaction force at the initial landing moment during jump-landing on the natural grass were significantly lower than those on the artificial turf(P＜0.05,P＜0.01),as well as at the peak ground reaction force moment(P＜0.05,P＜0.05).Additionally,the knee flexion moment when jump-landing on the natural grass was higher than that on the artificial turf(P＜0.01).In terms of electromyography,within 100 ms after the initial landing moment,the electromyography activity levels of medial femoris muscle,lateral femoris muscle and anterior tibialis muscle when jump-landing on the natural grass were significantly lower than those on the artificial turf(P＜0.05,P＜0.01,P＜0.05).To conclude,compared with the natural grass,jump-landing on the artificial turf leads to an change in biomechanical performance that will cause an increase in anterior cruciate ligament tension.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective To investigate the clinical characteristics,diagnosis and treatment of severe combined peri-odontal-endodontic lesions in a double-rooted maxillary lateral incisor with a palatal radicular groove and to provide a reference for clinical diagnosis and treatment.Methods A patient with a double-rooted left maxillary lateral incisor with a palatal radicular groove and severe combined periodontal-endodontic lesions underwent complete root canal thera-py and intentional replantation,and a retrospective analysis of the management of this type of patient was performed based on the literature.Results The 3-year follow-up examination revealed no discomfort,good healing of the upper left lateral incisor,no pathological loosening,and a palatal gingival sulcus was found at a depth of approximately 1 mm.Review of the literature showed that the prognosis of the affected tooth and the choice of treatment plan were correlated with the length and depth of extension of the lingual groove toward the root,the periodontal condition and the pulpal sta-tus of the affected tooth.For minor PRGs or for affected teeth with no loss of pulpal viability,flap surgery and odonto-plasty can be used to avoid endodontic treatment or retreatment.For deep or long lingual grooves that result in signifi-cant loss of periodontal tissue,endodontic treatment,odontoplasty,or closure of the grooves and guided tissue regenera-tion are needed.In the case of PRGs with double root formation,the affected tooth can be preserved via root canal thera-py,removal of the small root and filling with apical restorative material,and intentional replantation.Conclusion In cases of severe combined periodontal-endodontic lesions due to palatal radicular grooves occurring in double-rooted maxillary lateral incisors,clinical presentation and imaging can prevent missed diagnoses,and appropriate treatment should be based on the length and depth of lingual grooves extending toward the roots,periodontal conditions,and pulp-al status of the affected teeth.

Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P＜0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P＜0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P＜O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P＜0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.

[Objective]To elucidate the meridian manipulations described in the Han bamboo slips of Zhangjiashan from a meridian perspective,providing a theoretical foundation for the application of ancient meridian manipulations in modern clinical practice.[Methods]Based on the records in the unearthed literature and cultural relics of the pre-Qin,Qin and Han Dynasties,this paper summarizes the Daoyin technique in the pre-Qin,Qin and Han Dynasties,explores the in-depth relationship between Daoyin technique and meridian muscles,and selects the common orthopedic diseases in modern clinic,such as neck pain,ankle pain,knee pain and shoulder pain,which are closely related to meridian muscles.The original text and Daoyin movements are analyzed,and the Daoyin movements are discussed from the perspective of meridian muscles.[Results]It is found that the Daoyin described in the pre-Qin,Qin and Han Dynasties is mainly simple body movements.The meridians described in the Book of Pulse are mostly meridiansand tendons,so the theory of meridians and tendons may be more suitable for the thinking of the physicians at that time.Using the theory of meridians and tendons to analyze the Daoyin in Yinshu,it is found that the Daoyin therapy for neck pain in the book should be mainly treated for the neck pain of the sun meridian muscles;the treatment of lateral ankle pain is mainly adjusted by the Shaoyang meridian muscles of the foot,and the treatment of medial ankle pain is mainly adjusted by the Taiyin meridian muscles of the foot;the Daoyin therapy for knee pain is used to adjust the meridian muscles of the six meridians of the foot;the treatment of shoulder pain,the use of"Yuanxing three hundred"to treat the shoulder pain caused by the Shaoyang and Yangming meridian muscles of the hand,the use of"Qianyuan"to treat the shoulder pain caused by the sun meridian muscle disease,the use of"Zhiluo"to treat the shoulder pain caused by the sun meridian muscle disease,and the use of"Houfu"to treat the shoulder pain caused by the Taiyin meridian muscle disease.It is more reasonable to explain the treatment principles of Daoyin using the theory of meridian sinew,which can further elucidate the treatment principles of Daoyin and clarify the corresponding disease indications for different Daoyin.[Conclusion]Looking at the Daoyin manipulations in Yinshu from the perspective of meridians and tendons can further clarify the diseases treated by Daoyin manipulation,make the treatment more accurate and effective,and provide more ideas for the clinical application of Daoyin manipulation in modern traditional Chinese medicine.

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CX_AE, CX_AL, CX_PA and CX_PHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CX_AE, CX_AL and CX_PHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CX_AE and CX_PHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CX_PHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CX_PHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CX_PHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

Objective To investigate the effects of Polygonatum kingianum on wound healing and nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in diabetic skin injury rats.Methods Diabetic rat models were established and 48 rats were randomly divided into model group,sitagliptin group(10 mg·kg-1),Polygonatum kingianum water extract low dose group(2 g·kg-1),Polygonatum kingianum water extract high dose group(8 g·kg-1)and Polygonatum Kingianum alcohol extract low and high dose group(2 g·kg-1 and 8 g·kg-1).8 in each group;Another control group was set up.After 4 weeks of intragastric administration,all rats established back skin wounds,and continued to be administered for 14 days after operation.At the end of the experiment,the rats were killed,and blood glucose,glycosylated hemoglobin(GHb),plasma levels of H2O2,MDA,SOD,GSH and wound margin skin tissue T-AOC,SOD,MDA levels were measured.The relative expression of Nrf2 and HO-1 mRNA in wound margin skin tissue was measured by fluorescence quantitative method.Results Compared with the model group,the levels of SOD and GSH in plasma and the relative expressions of Nrf2 and HO-1 mRNA in wound margin skin tissue in the low and high dose groups of ethanol extract of Polygonatum kingianum,and the low and high dose groups of water extract of Polygonatum kingianum were increased(P<0.01,P<0.001).The levels of glycosylated hemoglobin(GHb)in plasma and MDA in wound margin tissue were decreased(P<0.05,P<0.01,P<0.001).The level of T-AOC in the high dose group was increased(P<0.01).The SOD level of skin tissue in the low dose group of Polygonatum kingianum water extract was increased(P<0.01),and the level of H2O2 in the low dose group was decreased(P<0.01).Conclusion Polygonatum canaliculatum can up-regulate Nrf2/HO-1 signaling pathway,regulate excessive oxidative stress,and promote wound healing.

Objective:To evaluate the value of whole-brain radiotherapy (WBRT) combined with simultaneous integrated boost (SIB) and WBRT plus sequential stereotactic radiosurgery (SRS) in the treatment of small-cell lung cancer (SCLC) patients with brain metastases (BM).Methods:A retrospective analysis was performed among 135 SCLC patients with BM who were admitted to Tianjin Medical University Cancer Institute and Hospital from 2007 to 2023. They all received cisplatin- or carboplatin-based first-line chemotherapy and WBRT with 94 patients receiving thoracic radiotherapy after chemotherapy. All patients were divided into the WBRT+SIB ( n=66) and WBRT+SRS groups ( n=69) according to the treatment methods. After propensity score matching (PSM), 63 patients were assigned into each group. The primary endpoints were overall survival (OS) and brain metastasis-related local control (BMRLC) rates. Categorical data, such as gender and age, were compared by Chi-square test. OS and BMRLC were calculated by Kaplan-Meier method. The survival curves between two groups were compared by log-rank test. The risk factors of OS and BMRLC were assessed by multivariate Cox regression models. Results:In all the patients, the median follow-up time was 24.9 (range 6.30-109.57) months. The 2-year OS and BMRLC rates were 49.0% and 85.0%, respectively. Cerebral necrosis occurred in 2 patients. Multivariate analysis revealed that shorter time interval of BM after diagnosis (≤10 months) ( P=0.041), control of extracranial progression ( P=0.029), and lower diagnosis-specific graded prognostic assessment (DS-GPA) (≥2) ( P=0.006) significantly improved OS. After PSM, the 2-year OS rate in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.041), while the 2-year BMRLC rate was not significantly improved ( P=0.203). In the DS-GPA<2 subgroup, the OS in the WBRT+SIB group was significantly higher than that in the WBRT+SRS group ( P=0.016), whereas no significant difference was observed in BMRLC between two groups ( P=0.205). In the DS-GPA≥2 subgroup, no significant difference was found in OS between two groups ( P=0.266), while BMRLC in the WBRT+SIB group was significantly lower compared with that in the WBRT+SRS group ( P=0.027). Conclusions:WBRT+SIB is more suitable for SCLC patients with BM than WBRT+SRS. However, WBRT+SRS yields higher local control for DS-GPA≥2 patients.

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
Humans ; Receptors, Chimeric Antigen/therapeutic use* ; Immunotherapy, Adoptive ; Hematologic Neoplasms/therapy* ; Treatment Outcome

OBJECTIVE To study active components and antitussive effect of aboveground part of Pinellia ternata （non- medicinal stems and leaves）， and compare them with the underground part of P. ternata （medicinal underground tubers）， providing scientific basis for the comprehensive utilization and product development of P. ternata. METHODS TLC， GC， HPLC and UPLC- MS/MS were used for qualitative and quantitative analysis of amino acids， volatile oil， total flavonoids and succinic acid from the aboveground and underground parts of P. ternata. The antitussive effects of the aboveground and underground parts of P. ternata were compared and studied through cough inducing experiment with concentrated ammonia water. RESULTS Results of TLC showed that at the corresponding positions on the chromatograms of the reference substances of P. ternata， and arginine， alanine， valine， leucine and rutin control， the aboveground and underground parts of P. ternata showed spots of the same color. Results of GC showed that the similarity among characteristic chromatograms of volatile oil from aboveground and underground parts of P. ternata was 0.767； results of HPLC and UPLC-MS/MS showed that compared with underground parts of P. ternata， the contents of succinic acid， quercetin， kaempferol and isorhamnetin increased by 0.15%， 0.15%， 0.09% and 0.03%， and aspartate content decreased by 2.5 mg/g. Pharmacodynamics results showed that compared with model control group， the cough incubation period of rats was prolonged significantly in administration groups （P＜0.05）， and the cough frequency within 3 min was significantly decreased （P＜0.05）； there was no statistical significance in the cough frequency within 3 min among administration groups （P＞0.05）. CONCLUSIONS The composition of amino acids， volatile oils and total flavonoids in aboveground part of P. ternata are similar to underground part of P. ternata， while the content of aspartic acid is lower than that in underground part. The aboveground part of P. ternata can prolong the cough incubation period of rats and reduce the number of coughs， which has a certain antitussive effect， but the effect is slightly weaker than that of the underground part.