Based on the analysis of the relevant records of the contralateral bloodletting technique, it is believed that this needling technique has 3 key characteristics, including "contralateral selection of points", "points on the four extremities dominated" and "collaterals selected rather than meridian points". Through the studies on philology and the annotation by the doctors in the past dynasties, a part of point prescriptions for the contralateral bloodletting is investigated, and those not belonged to the category of this needling technique in Suwen: Miuci Lun (On Contralateral Bloodletting) are distinguished. It is concluded that the failure of consensus-making in classifying point prescriptions is due to the lack of understanding on the characteristics of contralateral bloodletting and the misunderstanding on the errors of sentences and words. It is suggested that the study on theoretic concepts should lay on the problems relevant with the generalization and alienation of concepts. The mode of "combination of the detail with the whole" should be adopted. It starts from grasping the overall by systematic review, and followed by deliberating in details, so as to correctly identify the original concept and connotation.
Humans ; Bloodletting/methods* ; Acupuncture Points ; History, Ancient ; Meridians ; China

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment， liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this， this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis （ingredients such as ethanol extract of Euonymus alatus and paclitaxel， as well as compounds such as Ershiwuwei songshi pill and Ganfukang）， clear away heat and toxic material （ingredients such as betulinic acid， total flavonoids from Persicaria perfoliata， as well as compounds such as Pianzaihuang and Kehuang capsules）， and sooth the liver and promote qi circulation （ingredients such as fraxetin and cucurbitacin B， as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction） can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway， reducing inflammatory reactions， and inhibiting the proliferation of hepatic stellate cells.

ObjectiveTo investigate the effect of total glucosides of paeony （TGP） on neurotoxicity induced by aqueous extract of Strychni Semen （SA） in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group，SA group （19.5 mg·kg^-1），TGP group （225 mg·kg^-1），and SA+TGP group （SA 19.5 mg·kg^-1+TGP 225 mg·kg^-1）. The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde （MDA），glutamate （Glu） in the mouse brain tissue，and serum levels of 5-hydroxytryptamine （5-HT） were detected using enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes （DEGs） underwent gene ontology （GO） and kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group，the SA group exhibited significant increases in side-to-side distance and average speed in the open field test，as well as increased walking time on the balance beam. The axons of cortical neurons were absent，and the levels of Glu and MDA in the brain tissue were significantly elevated （P<0.05，P<0.01），along with a notable increase in serum 5-HT levels （P<0.05）. In contrast to the SA group，the SA+TGP group significantly reduced the side-to-side distance，average speed，and balance beam walking time （P<0.05 or P<0.01）. The neuronal axons were clearly visible，and levels of 5-HT，Glu，and MDA were decreased （P<0.05，P<0.01）. Transcriptome analysis indicated that TGP could regulate the glutamate receptor，ionotropic，N-methyl-D-aspartate 2a （GRIN2A）/phospholipase C β₁ （PLCB1）/protein kinase C，gamma （PRKCG） signaling pathway. Compared with the normal group，SA significantly decreased the expression of GRIN2A，PLCB1，and PRKCG genes in the mouse brain （P<0.01），while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration （P<0.05，P<0.01）. ConclusionSA induces significant neurotoxicity in the mouse brain，and TGP significantly alleviates SA-induced neurological damage，potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

Objective To assess the impact of statins combined with sorafenib(SRF)therapy on survival outcomes in patients with metastatic renal cell carcinoma(mRCC).Methods Clinical data of mRCC patients treated in the 908th Hospital of the Joint Security Force from November 2019 to November 2023 were retrospectively analyzed.They were categorized into statin group and non-statin group according to whether they used statins or not,and the differences in the primary endpoint of overall survival(OS),secondary endpoints of progression-free survival(PFS),objective response rate(ORR),and disease control rate(DCR)were compared between the two groups.Results A total of 80 patients were included in the study,with 27 in the statin group and 53 in the non-statin group.There were no statistically significant differences in partial remission,stable disease,disease progression,and DCR between the two groups(P＞0.05);complete remission and ORR were significantly higher in the statin group than in the non-statin group(P＜0.05).Kaplan-Meier analysis showed that,compared with the non-statin group,the median PFS and OS of the statin group were prolonged,and the difference in median PFS between the two groups was statistically significant(P＜0.05).In terms of safety,the incidence of other adverse events was similar in both groups(P＞0.05).Conclusion Statins combined with SRF treatment regimen can improve ORR and DCR and prolong median PFS and OS in patients with mRCC.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

Background/Aims: Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods: The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results: S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Objective: To explore the influence of music training on the response inhibition ability of children with developmental dysplasia, and to provide a theoretical basis for improving the response inhibition ability of children with developmental dyslexia. Methods: From September to October 2020, students from grades 3-6 in a primary school in Shenyang, Liaoning Province were selected. A total of 27 children with dyslexia were selected through literacy test and intelligence test, and 23 children with matched reading level were selected. The Go/No-go experimental paradigm was used to investigate the changes of response inhibition in children with developmental dyslexia before and after ALF music training, induding solfeggio, physical rhythm, music scene performance and chorus. Results: The results before and after music training showed that the main effect in the test stage was significant among two groups[ F(1,48)=6.13, P<0.05, η-p 2=0.11], and The accuracy of post-test [(91.80±0.80)%] was significantly higher than that of pre-test [(89.10±0.90)%]; the accuracy of the children with developmental dyslexia in response to the symbolic stimulus No-go was significantly higher in the post-test [(81.81±10.97)%] than in the pre-test [(73.78±15.26)%]( t =-2.33, P = 0.03 ); the accuracy of reading matched children s response to Chinese characters stimulation No-go was significantly better in the post-test [(85.59±12.11)%] than in the pre-test [(78.33±12.98)%]( t = -2.20, P <0.05). In terms of response time, the post-test scores of developmental dyslexia children [(444.06±77.49)ms] were significantly better than those of pre-test children [(519.01±70.75)ms], and there was no significant difference between symbol stimulus and Chinese stimulus in developmental dyslexia children ( P>0.05). Conclusion Response inhibition is deficient in children with developmental dyslexia. Compared with symbols, the response inhibition ability of Chinese characters is impaired; Music training significantly improved the inhibitory ability of signs in children with developmental dyslexia.