ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin complex 1 （mTORC1） signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules， while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate （PR）， total sperm motility （PR+NP）， percentage of normal mitochondrial membrane potential （MMP）， and traditional Chinese medicine （TCM） symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally， eight patients were randomly selected from the eligible patients in the observation group， and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK， phosphorylated （p）-AMPK， regulatory-associated protein of mTOR （RAPTOR） and p-RAPTOR， and PTEN-induced putative kinase 1 （PINK1） in sperms from the observation group before and after treatment， as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% （3/33）， which was higher than that （3.33%， 1/30） in the control group. The total response rate was 84.8% （28/33） in the observation group and 66.7% （20/30） in the control group， with no statistically significant difference. After treatment， both groups were improved considering PR， PR+NP， MMP， and TCM symptom scores （P<0.01）. Moreover， the observation group exhibited more pronounced decreases in TCM symptom scores than the control group （P<0.05）， while the changes in PR， PR+NP， and MMP showed no statistical significance between groups. Compared with the control group， the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK （P<0.01）. The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 （P<0.01）. However， the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period， neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway， lowering the protein level of PINK1， and inhibiting excessive activation of mitophagy.

The 2024 World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) Annual Meeting, two of the most prestigious events in oncology, have concluded sequentially. As the most authoritative annual gatherings in lung cancer and the entire oncology field, the WCLC and ESMO conferences brought together top oncology experts and scientists from around the world to share, discuss, and publish the latest cutting-edge advancements in oncology. In both conferences, lung cancer immunotherapy remained a hot topic of considerable interest. This article aims to summarize and discuss the important research progress on perioperative immunotherapy for non-small cell lung cancer reported at the two conferences.

OBJECTIVE: To investigate the effectiveness of TiRobot-assisted minimally invasive treatment for fragility fractures of the pelvis (FFP) in elderly patients. METHODS: A retrospective analysis was conducted on the clinical data of 176 patients with FFP who were admitted between July 2018 and July 2024 and met the selection criteria. Among them, 95 patients underwent TiRobot-assisted closed reduction and minimally invasive cannulated screw fixation (robot group), while 81 patients underwent traditional open reduction and plate screw fixation (control group). There was no significant difference in baseline data such as gender, age, fracture classification, disease duration, and preoperative visual analogue scale (VAS) pain scores between the two groups ( P>0.05). The following parameters were recorded and compared between the two groups, including operation time, intraoperative blood loss, intraoperative transfusion rate, volume of intraoperative blood transfusion, maximum incision length, hospital stay, maximum residual displacement, reduction quality, fracture healing time, incidence of complications, VAS scores, Majeed pelvic function scores, and functional grading. RESULTS: All surgeries in both groups successfully completed. The robot group exhibited significantly shorter operation time, reduced intraoperative blood loss, lower intraoperative transfusion rate, smaller volume of intraoperative blood transfusion, shorter maximum incision length, and shorter hospital stay compared to the control group ( P<0.05). In the robot group, a total of 14 INFIX internal fixation frames and 280 cannulated screws were implanted, among which 250 screws were rated as excellent, 17 as good, and 13 as poor, resulting in a screw placement excellent and good rate of 95.36%. Radiological review revealed that the excellent and good rate of reduction quality was in 91.58% (87/95) in the robot group and 81.48% (66/81) in the control group, with no significant difference in postoperative maximum residual fracture displacement or reduction quality between the two groups (P>0.05). All patients in both groups were followed up 12-66 months, with an average of 28.9 months, and there was no significant difference in follow-up time between the two groups ( P>0.05). The fracture healing time in the robot group was significantly shorter than that in the control group ( P<0.05). At last follow-up, both groups showed significant improvement in VAS scores compared to preoperative values ( P<0.05); the change values of VAS scores, Majeed scores, and the excellent and good rate of Majeed pelvic function were significantly higher in the robot group than in the control group ( P<0.05). Regarding postoperative complications, there was no significant difference between the two groups in terms of gait changes, secondary surgeries, heterotopic ossification, incision infections, walking difficulties, internal fixation failure, or mortality rates ( P>0.05); however, the incidence of delayed wound healing was significantly lower in the robot group than in the control group ( P<0.05). CONCLUSION TiRobot-assisted minimally invasive treatment of elderly FFP is superior to traditional open reduction and internal fixation in terms of surgical trauma control, postoperative rehabilitation speed, and functional recovery.
Humans ; Male ; Retrospective Studies ; Female ; Minimally Invasive Surgical Procedures/instrumentation* ; Fracture Fixation, Internal/instrumentation* ; Pelvic Bones/surgery* ; Aged ; Bone Screws ; Bone Plates ; Robotic Surgical Procedures/methods* ; Aged, 80 and over ; Treatment Outcome ; Osteoporotic Fractures/surgery* ; Operative Time ; Blood Loss, Surgical ; Fracture Healing ; Fractures, Bone/surgery*

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Objective To explore the role of transcription factor EB(TFEB)induced by aerobic exer-cise in improving insulin resistance(IR)of skeletal muscles in high-fat diet mice.Method Eighteen male SPF C57BL/6 mice aged 6 weeks were randomly divided into a common diet group(CON),a high-fat diet group(HFD),and a high-fat diet exercise group(HFDE),each of 6.Both high-fat groups were on high-fat diet for 12 weeks.Then the HFDE group underwent daily 60-minute tread-mill exercise with the slope of 0°,at a speed of 12 m/min,5 times per week for 12 weeks.Finally,the glucose tolerance and insulin sensitivity were detected using the intraperitoneal injection glucose tol-erance test(IPGTT)and intraperitoneal injection insulin tolerance test(IPITT).The fasting blood glu-cose and insulin contents were measured by biochemical method,and the IR level was calculated by using the homeostatic model assessment of insulin resistance(HOMA-IR).Moreover,Western blotting was employed to detect the expression of phosphorylated transcription factor EB(pTFEB)and TFEB in skeletal muscle,glucose transporter 4(GLUT4)in cytoplasm and membrane,phosphorylated insulin re-ceptor substrates1(pIRS1),phosphorylated protein kinase B(pAKT),phosphoinositide 3-kinase(PI3K),and phosphorylated akt substrate of 160 kD(pTBC1D4)in skeletal muscle.The correlation of pTFEB and TFEB to insulin signaling pathway-related proteins was analyzed.Results(1)Compared with the CON group,there was a significant increase in the average body weight,IPGTT,blood glucose at each time point of IPGTT,area under curve(AUC),serum insulin,HOMA-IR,protein expressions of pTFEB,total-TFEB and GLUT4 in cytoplasm of the HFD group(P<0.01),but a significant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane of skeletal muscles(P<0.01).However,no significant differences were found between the two groups in the average expression of pTFEB and T-TFEB proteins.(2)Compared to the HFD group,a signifi-cant increase was found in the average body weight,blood glucose at each time point of IPGTT,blood glucose of IPITT at 0 min,30 min and 60 min and AUC,serum insulin,HOMA-IR,expres-sions of pTFEB,T-TFEB and GLUT4 in cytoplasm of HFDE group(P<0.05 or P<0.01),with a signifi-cant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane and T-TFEB in nucleus(P<0.01).(3)TFEB was negatively correlated with the expres-sion of pIRS1,PI3K,pAKT,and pTBC1D4 proteins(r=-0.8642,r=-0.7789,r=-0.8946,r=-0.8040)but positively correlated with cytoplasmic GLUT4(r=0.8532,P<0.01).Moreover,TFEB in the nucleus was of positive correlation with GLUT4 in the cell membrane(r=0.7744,P<0.01).Conclusions High-fat diet can decrease the expression of insulin signaling pathway related proteins in skeletal mus-cles of mice and weaken their insulin action,leading to the disorder of glucose and lipid metabolism.However,aerobic exercise can significantly increase the expression of such proteins to promote insulin function and sensitivity,and relieve disorders in glucose and lipid metabolism.This effect may be achieved through the promotion of skeletal muscle TFEB nuclear translocation,which activates IRS1/PI3K/AKT/TBC1D4/GLUT4 signaling pathway and facilitates GLUT4 membrane translocation,ultimately enhancing glucose uptake in skeletal muscle cells.The authors speculate that the TFEB-mediated insu-lin signaling pathway may be an important molecular pathway for aerobic exercise to improve insulin re-sistance.

Objective To observe the feasibility of 5.0T MR for cardiac imaging.Methods Three patients with heart diseases and 17 healthy volunteers were prospectively enrolled.Cardiac MR(CMR)cine sequence and black blood sequence imaging were performed using 5.0T and 3.0T MR scanner,respectively.The image quality and artifacts degrees were compared between 5.0T and 3.0T CMR images,and the consistency of left ventricular parameters obtained using 5.0T and 3.0T scanners was analyzed.Results No significant difference of image quality nor artifacts degrees was found between 5.0T and 3.0T CMR images(all P＞0.05).The left ventricular end diastolic volume(EDV),end systolic volume(ESV),ejection fraction(EF),stroke volume(SV)and end diastolic mass(EDM)derived from cine images acquired at different fields were in a good agreement(all ICC＞0.75,all P＜0.001).Conclusion 5.0T MR could be used for cardiac imaging,with image quality of cine and black blood sequences comparable to that of 3.0T MR.

Objective To observe the value of susceptibility weighted imaging(SWI)based on 5.0T MRI for diagnosing hepatocellular carcinoma(HCC)complicated with vein tumor thrombi.Methods Totally 63 HCC patients were retrospectively enrolled,among them 17 complicated with vein tumor thrombi.The efficacy of 5.0T SWI for detecting vein tumor thrombus was observed,and the image quality were compared between 5.0T and 3.0T.Results 5.0T SWI displayed vein tumor thrombi in 16 cases,except for 1 case with vein tumor thrombi in the upper segment of the left lateral lobe of the left portal vein.The liver edge score,overall image quality score,signal-to-noise ratio and contrast-to-noise ratio of portal venous phase and hepatobiliary phase in 5.0T enhanced MRI were all higher than those in 3.0T(all P＜0.05).Conclusion 5.0T SWI was helpful for diagnosing HCC complicated with vein tumor thrombi.

Objective:To investigate the correlation between serum albumin, urea nitrogen and Fazekas scores and cognitive function scores in patients with mild and medium ischemic stroke.Methods:Clinical data of 160 patients with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS)≤7 scores admitted to the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from June 2021 to April 2023 were selected for a cross-sectional study. According to the Montreal Cognitive Assessment (MoCA) score, they were divided into normal cognitive group (28 cases) (MoCA≥26 scores), mild to moderate cognitive impairment group (74 cases) (MoCA 15-<26 scores), and severe cognitive impairment group (58 cases) (MoCA<15 scores). Demographic characteristics, serological indicators and imaging data of patients were collected, and the correlation between serum albumin, urea nitrogen and Fazekas scores and the total score of MoCA and the scores of each cognitive domain was analyzed. One-way ANOVA was used for comparison between the normal distribution and homogeneous variance data sets, LSD analysis was used for pairwise comparison, Kruskal-Wallis H test was used between the skew distribution or heterogeneous variance data sets. Bonferroni correction analysis was used for pairwise comparison. Chi-square test or Fisher exact probability method was used after the comparison between the count data sets. Spearman Spearman correlation analysis was performed on serum albumin, urea nitrogen and Fazekas scores with MoCA scores and cognitive domain scores. Multivariate ordered Logistic regression was used to analyze the independent risk factors of cognitive function in acute stage of mild and medium ischemic stroke patients. Results:The incidence of cognitive impairment in patients with acute mild and medium ischemic stroke was 82.50% (132/160). Comparison of age ((56.71±7.35), (60.32±10.20), (66.40±11.88) years old), sex (male/female: (23/5, 58/16, 33/25)), the proportion of education level above high school (25.0%(7/28), 16.2%(12/74), 6.9%(4/58)), hemoglobin ((149.26±14.91), (144.85±16.85), (137.63±17.22) g/L), albumin (39.5 (37.0, 41.2), 38.6(35.6, 40.8), 37.4 (34.5, 39.8) g/L), urea nitrogen (5.30 (4.00, 6.60), 4.81 (4.00, 6.32), 5.86 (4.55, 6.97) mmol/L), Hamilton Anxiety Scale (HAMA) score (5.0 (2.0, 10.0), 7.5 (5.0, 11.0), 10.0 (6.0, 14.3) scores),Hamilton Depression Scale (HAMA) score (5.5 (3.0, 12.5), 7.0 (4.0, 11.0), 9.5 (5.0, 14.0) scores), and Fazekas score (2.00 (1.25, 3.00), 2.00 (1.00, 4.00), 3.00 (2.00, 5.00) scores) among cognitive normal group, mild to moderate cognitive impairment group, and severe cognitive impairment group of patients, the difference were statistically significant (the statistical values were F=9.68, χ 2=9.29, χ 2=30.77, F=5.31, H=7.06, H=6.71, H=12.37, H=8.91, and H=10.96, respectively;the P values were <0.001, 0.010, <0.001, 0.006, 0.029, 0.035, 0.002, 0.012, and 0.004, respectively ). The total score of MoCA was negatively correlated with Fazekas score and serum urea nitrogen, but positively correlated with serum albumin ( r s values were -0.250, -0.168, and 0.212, respectively; P values were 0.001, 0.036, and 0.009, respectively). Serum albumin was positively correlated with scores in visual space and execution, naming, attention and orientation, serum urea nitrogen was negatively correlated with scores in language and orientation, and Fazekas score was negatively correlated with scores in visual space and execution, orientation, attention and language ( r s values were 0.291, 0.196, 0.191, 0.209, -0.205, -0.180, -0.248, -0.193, -0.188, and -0.183, respectively; P values were <0.001, 0.017, 0.020, 0.011, 0.012, 0.027, 0.002, 0.016, 0.020, and 0.023, respectively). Multiple Logistic regression analysis showed that low albumin ( OR=0.884, 95% CI: 0.813-0.963, P=0.005) and high urea nitrogen ( OR=1.195, 95% CI: 1.003-1.425, P=0.047) and high Fazekas scores ( OR=1.401, 95% CI: 1.132-1.733, P=0.002) were independent risk factors for cognitive function, while high education level was a protective factor ( OR=0.062, 95% CI: 0.019-0.202, P<0.001). Conclusion:The incidence of acute cognitive impairment is high in patients with mild and medium ischemic stroke. Higher education level is a protective factor for cognitive function. Low albumin, high urea nitrogen and high Fazekas score are independent risk factors for cognitive function.