BACKGROUND:Acupuncture is an effective method for lumbar pain in lumbar disc herniation,but its mechanism has not yet been clarified.Factors related to the JAK2/STAT3 signaling pathway regulate the body's inflammatory response and are involved in the process of neuropathic pain. OBJECTIVE:To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:sham operation group,model group,acupuncture group,and acupuncture+agonist group,with 10 rats in each group.Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group,acupuncture group,and acupuncture+agonist group.Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment(Yanglingquan,Shenshu,Huantiao,and Dachangshu acupoints)at 3 days after modeling,and acupuncture treatment was given once a day,20 minutes each,for 15 consecutive days.Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1,a JAK2 agonist,into the L4/L5 intervertebral space,once a day,20 minutes each,prior to the acupuncture at 6,12,and 18 days after modeling.Paw withdrawal mechanical threshold was detected before and 3,6,9,12,15,and 18 days after modeling.At 18 days after modeling,serum inflammatory factor levels were detected,hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues,RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues,and western blot was performed to detect the expression of JAK2,p-JAK2 and p-STAT3 proteins in L5-L6 tissues. RESULTS AND CONCLUSION:The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group(P<0.05),the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9,12,15,and 18 days after modeling(P<0.05),and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9,12,15,and 18 days after modeling(P<0.05).The levels of interleukin 6,tumor necrosis factor α,neurotransmitter substance P,and brain neuropeptide Y were elevated in the model group compared with the sham operation group(P<0.05);the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group(P<0.05);and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group(P<0.05).Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group.Moreover,the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group.The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group(P<0.05),were decreased in the acupuncture group compared with the model group(P<0.05),and were increased in the acupuncture+agonist group compared with the acupuncture group(P<0.05).To conclude,acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation,and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Objective: To identify the core symptoms and bridge symptoms in the network structure among adolescents bullying victimization, anxiety and depressive symptoms, and to explore the interrelationships among these three variables, so as to provide a basis for the precise prevention of bullying behaviors and the improvement of adolescents psychological health conditions. Methods: From October to November 2023, a stratified cluster random sampling method was employed to select 4 759 middle and high school students from four cities in Guangxi: Beihai, Guigang, Hechi, and Laibin. The Chinese version of the Olweus Bully/Victim Questionnaire (OBVQ) was used to assess bullying victimization among adolescents, while the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were utilized to assess anxiety and depressive symptoms, respectively. The Bootnet package (version 1.6) in R software (version 4.4.1) was used to construct a network structure and analyze the associations between bullying victimization, anxiety symptoms and depressive symptoms among adolescents. Results: The reporting rates of depressive symptoms, anxiety symptoms, and bullying victimization among adolescents in Guangxi were 24.67%, 16.33%, and 16.58%, respectively. Network analysis revealed that the node with the highest expected influence was "property being taken or damaged", with a standardized expected influence (EI) index of 2.09. The top two nodes in terms of bridge expected influence were "thoughts of self harm or suicide" and "irritability", with standardized bridge expected influence (BEI) indices of 2.15 and 1.27, respectively. The stronger associations were observed between the node "property being taken or damaged" and the nodes "physical attacks such as hitting, kicking, pushing, or shoving" and "ridiculed due to accent", with edge weights of 0.43 and 0.35, respectively. Conclusion Targeting preventive measures against the symptoms with the highest expected influence and bridge expected influence in the network of bullying victimization, anxiety and depressive symptoms among adolescents may be an effective approach to reduce the negative impact of bullying victimization, anxiety and depressive symptoms on adolescents.

This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Pleural mesothelioma （PM） is a rare malignant tumor originating from the pleura. Most patients are already in the advanced stage at the time of diagnosis， resulting in a low overall survival rate. MicroRNA （miRNA）， as key regulators of tumor epigenetic modification， have an intertwined interactive network with PM drug resistance. The mechanisms of drug resistance in PM to chemotherapeutic drugs include increasing drug efflux， reducing drug intake， enhancing DNA repair， and altering drug targets. The mechanisms of resistance to targeted therapy drugs include activating alternative signaling pathways， establishing a favorable tumor microenvironment， and triggering epithelial-mesenchymal transition. MiRNA plays a key part in the aforementioned resistance mechanisms， with some miRNAs promoting the drug sensitivity of cancer cells， while others contribute to increased drug resistance. In light of these key regulatory functions， targeting the dysregulated expression of endogenous miRNAs in the process of resistance formation using miRNA antagonists or miRNA mimics may be an effective therapeutic strategy to reverse drug resistance in PM.

Objective:To explore the effects of pre-transplant controlling nutritional status(CONUT)and post-transplant minimal residual disease(MRD)on prognosis of patients with multiple myeloma(MM)after autologous hematopoietic stem cell transplantation(auto-HSCT).Methods:The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed.The patients were divided into Low-CONUT group(n=62)and High-CONUT group(n=17)according to whether the CONUT score was less than 5.The differences in clinical features,hematopoietic reconstruction,adverse reactions,efficacy and survival between the two groups were compared.In addition,the prognostic risk factors were analyzed and verified by time-dependent ROC curve.Results:The proportions of male patients and bone marrow plasma cells＞30％at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group(both P＜0.05).While,there were no significant differences in hematopoietic reconstruction and adverse reactions(＞grade 2)between the two groups.The complete response(CR)rate and CR+very good partial response(VGPR)rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group(both P＜0.05).After 3 months of transplantation,the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group(P＜0.01),but CR rate did not(P＞0.05).The overall survival(OS)and progression-free survival(PFS)in Low-CONUT group were both superior to those in High-CONUT group(both P＜0.05).Low CONUT score(0-4)before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS(both P＜0.05),while the International Myeloma Working Group(IMWG)high-risk at initial diagnosis and lactate dehydrogenase(LDH)level＞250 U/L before transplantation were only risk factors for PFS(both P＜0.05).Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1-and 2-year OS and PFS,and the combined prediction was more effective.Conclusion:The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the effect of auricular pressure beans(APN)combined with Compound Tung-Leaf Burn Oil(CTBO)on perioperative anxiety and pain in patients undergoing circumcision.Methods:This study included 100 patients undergo-ing circumcision with the disposable circumcision anastomosis stapler in our hospital from August 2023 to November 2023,of whom 50 received routine circumcision nursing care(the control group)and other 50 APN combined with compound CTBO in addition(the ob-servation group).We compared between the two groups the anxiety scores before any intervention,30 minutes before and 24 hours and 10 days after operation,the pain scores 24 hours postoperatively and at the first change of wound dressing,the frequency of 3-day post-operative sleep awakenings,the incidence of complications,and the satisfaction of the patients.Results:Totally,94 patients com-pleted the study,46 in the observation and 48 in the control group.The anxiety scores exhibited no statistically significant difference between the two groups of patients before any intervention(P>0.05),but were markedly lower in the observation than in the control group at 30 minutes before and 24 hours and 10 days after surgery(P<0.05),and so were the pain scores24 hours after surgery and at the first change of wound dressing(P<0.05),and the frequency of 3-day postoperative sleep awakenings(P<0.05).The satis-faction rate of the patients was remarkably higher(P<0.05)while the incidence of complications significantly lower in the observation group than in the control(P<0.05).Conclusion:Auricular pressure beans combined with Compound Tung-Leaf Burn Oil can ef-fectively alleviate perioperative anxiety,reduce postoperative pain and improve satisfaction of the patients undergoing circumcision.