Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

Objective To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. Methods All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. Results A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. Conclusions The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.

Objective To construct a universal influenza mRNA vaccine and evaluate its immunogenicity.Methods The antigen sequence of hemagglutinin(HA),nucleoprotein(NP)and matrix protein 2 ectodomain(M2e)in influenza A/California/04/2009 was optimized.HA,NP and 3 tandem M2e(3M2e)were cloned into pcDNA3.1 vector,respectively.Then the mRNAs were synthesized by linearization,in vitro transcription,enzymatic capping and enzymatic tailing,and named as mRNA-HA,mRNA-NP and mRNA-3M2e,respectively.The protein expression of the 3 kinds of mRNAs in 293T cells was detected by immunofluorescence assay.Comb-mRNA vaccine was prepared by enveloped mRNA-HA,mRNA-NP and mRNA-3M2e with lipid nanoparticles,respectively,and the particle size and potential were identified.Twenty-eight 6-week-old female BALB/c mice(18～22 g)were randomly divided into LNP group(n=14)and Comb-mRNA group(n=14).Hemagglutination inhibition(HI)method and microneutralization(MN)test were used to evaluate the serum antibody titer induced by Comb-mRNA vaccines.The mice were infected by 5LD50 wild-type H1 N1 influenza virus to evaluate the protective efficacy.Results The mRNA-HA,mRNA-NP and mRNA-3M2e were successfully constructed,and the 3 mRNAs could be expressed in 293T cells.The average size of mRNA encapsulated by lipid nanoparticles was 119.53±6.5 nm,and the average potential was-8.23±1.3 mV.The geometric mean titer(GMT)of HI and MN in the Comb-mRNA group were 179.6 and 201.6,compared with the LNP group.The ratio of IFN-γ+CD4+/CD8+Tcells was increased.The Comb-mRNA group could provide protection against 5LD50 wild type influenza H1 N1 virus after 2 weeks of booster immunization.Conclusion Comb-mRNA,an influenza vaccine candidate,can induce immune responses and protect mice from influenza virus challenge.

Objective:To explore the effects of aerobic exercise on learning and memory functions, hippocampal synaptic plasticity and the ADPN signaling pathway in diabetic rats.Methods:6-week-old male SD rats were randomly divided into a blank control group(NC group)and a high-fat diet group, and a rat model for diabetes was induced by feeding rats in the high-fat diet group with a high-fat diet combined with intraperitoneal instillation of low-dose streptozotocin(STZ)for 5 weeks.Rats in the high-fat diet group were further divided into a diabetic group(DC group)and a diabetic aerobic exercise group(DM group)after successful establishment of the model.Rats in the DM group were subjected to aerobic exercise for eight weeks and then the Morris water maze test was conducted to assess learning and memory functions, relevant serum markers were measured, Golgi staining was used to examine synaptic changes in the hippocampus, and Western blot was carried out to detect hippocampal protein expression levels of adiponectin(ADPN), AMP-activated protein kinase(AMPK), glucose transporter 4(GLUT4), synaptic plasticity-related protein synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)for rats in each group.Results:Serum FBG and HBA1c in diabetic rats were markedly significantly decreased after 8 weeks of aerobic exercise( P<0.01), and serum ADPN and insulin were significantly increased after 8 weeks of aerobic exercise( P<0.05).When test results from the three groups of rats compared, the F value was 69.248 for FBG, 6.740 for INS, 7.017 for HBA1C and 14.315 for serum ADPN.The results of the water maze test and hippocampal Golgi staining showed that the escape latency of diabetic rats was highly significantly decreased after 8 weeks of aerobic exercise( P<0.01).The platform crossing times, the number of dendritic branches and the dendritic spine density in the hippocampal CA3 region of diabetic rats were significantly increased after 8 weeks of aerobic exercise( P<0.05).When results from the three groups of rats were compared, the F value was 13.934 for escape latency, 5.864 for platform crossing times, 9.307 and 6.734 for the number of dendritic branches and the density of dendritic spine in hippocampal CA3 region.Hippocampal PSD-95, SYN, ADPN, p-AMPK, and GLUT4 protein expression levels of diabetic rats were significantly increased( P<0.05)after 8 weeks of aerobic exercise.When results from the three groups of rats were compared, the F value was 15.137 for SYN, 5.415 for PSD-95, 9.687 for ADPN, 27.761 for GLUT4, and 9.298 for p-AMPK. Conclusions:Eight weeks of aerobic exercise can improve the learning and memory functions of diabetic rats, and the mechanisms may be related to exercise-induced hippocampal ADPN/AMPK/GLUT4 signaling activation in rats, leading to enhanced synaptic plasticity in the hippocampus.

Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) on postoperative acute kidney injury (AKI) in elderly patients undergoing long-time abdominal surgery.Methods:The medical records from elderly patients of both sexes, aged ≥ 65 yr, with a duration of operation ≥ 8 h and American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective first abdominal surgery for gastrointestinal tumors at the Shanxi Provincial People′s Hospital from October 1, 2016 to June 30, 2022, were collected from the electronic medical record database. Patients were divided into conventional fluid therapy group (group C) and GDFT group (group G) according to whether GDFT was employed during operation. In group C, blood pressure was maintained ≥90/60 mmHg or mean arterial pressure≥65 mmHg, and urine output more than 30 ml/h. In group G, the stroke volume variation was maintained ≤13%, and cardiac index ≥2.5 L·min -1·m -2. The patient general characteristics, requirement for fluid, urine output, blood loss, requirement for vasoactive agents and abdominal hyperthermic perfusion, and operation time were recorded during operation. The development of AKI within 72 h after operation and development of other complications (pneumonia, anastomotic leakage, surgical site infection, septic shock, arrhythmia) after operation were recorded. The length of hospital stay and 30-day mortality after operation were recorded. Results:A total of 125 patients were included in this study, with 41 patients in group C and 84 patients in group G. Postoperative AKI occurred in 19 patients, with an incidence of 15.2%. Compared with group C, the requirement for colloid, total volume of fluid infused and urine volume were significantly decreased during operation, the requirement for vasoactive agents was increased during operation ( P<0.05), the risk of postoperative AKI was reduced ( OR=0.23, P<0.05), and no significant change was found in the incidence of other postoperative complications, 30-day mortality, and length of hospital stay in group G ( P>0.05). Conclusions:GDFT can reduce the risk of AKI in the elderly patients undergoing long-time abdominal surgery.

Objective:To compare the surgical outcomes of robotic natural orifice specimen extraction surgery (NOSES) and robotic-assisted radical resection for rectal cancer.Methods:A retrospective analysis using propensity score matching (PSM) was conducted on 547 patients who had undergone radical resection of rectal cancer at the First Affiliated Hospital of Nanchang University from June 2018 to March 2024. The study cohort comprised 157 patients in the robotic NOSES group and 390 in the robotic-assisted group. PSM was used in a 1:1 manner to match relevant general clinical preoperative data of the study patients (age, sex, body mass index, preoperative comorbidities, abnormal preoperative carcinoembryonic antigen (>6.5 μg/L) and carbohydrate antigen 19-9 levels (>27 kU/L), preoperative American Society of Anesthesiologists score, tumor diameter, tumor distance from the anal margin, and TNM stage), with a clamp value of 0.05. After performing PSM to match the general clinical data of the two groups of patients, 77 patients in each of the robotic NOSES and robotic-assisted groups were included in the analysis. We found no statistically significant difference in preoperative general clinical data between the robot NOSES and robot-assisted groups ( P>0.05). We compared the surgical outcomes, postoperative recovery, postoperative pathological data, and incidence of complications between the robotic NOSES and robot-assisted groups. Results:Compared with the robot-assisted groups. the robot NOSES group had a significantly shorter time to first postoperative passage of flatus (48 [38, 50] hours vs. 56 [50, 60] hours, Z=-7.513, P<0.001), time to taking a liquid diet (60 [54,63] hours vs. 66 [62, 72] hours, Z=-6.303, P<0.001), lower pain scores (3 [3, 4] vs. 4 [4, 5], Z=-5.237, P<0.001), and lower incision infection rates (0 vs. 5 [6.5%], χ 2=5.237, P=0.028) within 24 hours after surgery ( P<0.05). However, there were no significant differences in surgical time, intraoperative blood loss, postoperative hospital stay, postoperative anastomotic complications, or incidence of other complications between the two groups (all P>0.05). Conclusion:Robotic NOSES surgery is a safe and feasible procedure for resecting rectal cancer and postoperative recovery is faster after robotic NOSES than after standard robot-assisted surgery.

Objective:To compare the surgical outcomes of robotic natural orifice specimen extraction surgery (NOSES) and robotic-assisted radical resection for rectal cancer.Methods:A retrospective analysis using propensity score matching (PSM) was conducted on 547 patients who had undergone radical resection of rectal cancer at the First Affiliated Hospital of Nanchang University from June 2018 to March 2024. The study cohort comprised 157 patients in the robotic NOSES group and 390 in the robotic-assisted group. PSM was used in a 1:1 manner to match relevant general clinical preoperative data of the study patients (age, sex, body mass index, preoperative comorbidities, abnormal preoperative carcinoembryonic antigen (>6.5 μg/L) and carbohydrate antigen 19-9 levels (>27 kU/L), preoperative American Society of Anesthesiologists score, tumor diameter, tumor distance from the anal margin, and TNM stage), with a clamp value of 0.05. After performing PSM to match the general clinical data of the two groups of patients, 77 patients in each of the robotic NOSES and robotic-assisted groups were included in the analysis. We found no statistically significant difference in preoperative general clinical data between the robot NOSES and robot-assisted groups ( P>0.05). We compared the surgical outcomes, postoperative recovery, postoperative pathological data, and incidence of complications between the robotic NOSES and robot-assisted groups. Results:Compared with the robot-assisted groups. the robot NOSES group had a significantly shorter time to first postoperative passage of flatus (48 [38, 50] hours vs. 56 [50, 60] hours, Z=-7.513, P<0.001), time to taking a liquid diet (60 [54,63] hours vs. 66 [62, 72] hours, Z=-6.303, P<0.001), lower pain scores (3 [3, 4] vs. 4 [4, 5], Z=-5.237, P<0.001), and lower incision infection rates (0 vs. 5 [6.5%], χ 2=5.237, P=0.028) within 24 hours after surgery ( P<0.05). However, there were no significant differences in surgical time, intraoperative blood loss, postoperative hospital stay, postoperative anastomotic complications, or incidence of other complications between the two groups (all P>0.05). Conclusion:Robotic NOSES surgery is a safe and feasible procedure for resecting rectal cancer and postoperative recovery is faster after robotic NOSES than after standard robot-assisted surgery.

Vector flow imaging(VFI)is an innovative ultrasound flow measurement technology.Compared with the traditional color Doppler and spectral Doppler,VFI has the advantages of independence of angle correction and direct acquisition of real-time amplitude and direction of flow.Transverse oscillation(TO)method is one of the effective methods for vector flow imaging.However,a complete and detailed algorithm validation process based on commercial ultrasound machines is still lacking due to more complex convex probes.This study starts with introducing the imaging process and principle of transverse oscillation vector flow technique,and calculates the error between the set velocity value and the measured velocity value through the simulation experiment,and verifies the error between the set velocity value and the measured velocity value through the Doppler flow phantom experiment.Among them,the velocity value measured by the TO vector flow technique in the simulation experiment is 0.48 m/s and the preset value is 0.50 m/s,the error between them is-4％.The velocity values are 8.33,11.14,14.44 and 16.67 cm/s measured by the Doppler flow phantom experiment,the actual velocity values are 7.97,10.78,14.06 and 17.34 cm/s,the errors between them are all within±5％.Both experiments verify the feasibility of using vector flow technique on abdominal convex probe.

Objective To investigate the role and possible mechanisms of transactive response DNA binding protein 43 (TDP-43)in mediating neuronal injury induced by oxidative stress in mouse neuro-2a (N2a)cells and mouse pain sensitization.Methods ①To evaluate the optimal induction concentration,N2a cells were treated with different concentrations of H2O2,and the cells were divided into control group,200,400 and 800 μmol/L H2O2 groups.②To assess the optimal induction duration,N2a cells were treated with 400 μmol/L H2O2,and the cells were divided into control group,and the cell groups treated for 6,12 and 24 h,respectively.③To validate the mitochondrial DNA (mtDNA)release pathway,cyclosporin A (CsA) was used to inhibit the mitochondrial permeability transition pore (mPTP),and the cells were divided into control group,24 h H2O2 group and 24 h H2O2+CsA group.④To validate TDP-43-mediated cellular damage,the cells were divided into control group,24 h H2O2 group and 24 h H2O2+siTDP-43 group.⑤Cell viability was assessed using CCK-8 assay,while cell proliferation was determined using EdU assay.Western blot analysis was employed to examine the expression levels of TDP-43,neuronal nuclei (NeuN),cyclic GMP-AMP synthase (cGAS),and stimulator of interferon genes (STING).qPCR was utilized to measure the release of mtDNA.Immunostaining was conducted to observe intracellular expression of TDP-43,and Calcein AM staining was employed to evaluate mPTP opening status.⑥To elucidate the role of TDP-43 in neuropathic pain (NP),24 healthy SPF male C57BL/6J mice (6～8 weeks old,25～30 g)were randomly divided into control group,chronic constriction injury (CCI)group,and CCI+siTDP-43 group.In 1 d before and 7,14 and 21 d after surgery,intrathecal injections of siTDP-43 were administered.Mechanical and thermal pain thresholds of the mice were assessed using von Frey filaments and radiant heat,respectively,on 1 preoperatively and 1,3,5,7,14 and 21 d postoperatively.Immunofluorescence assay was conducted on 21 d postoperatively to examine the changes in TDP-43 and NeuN in the lumbar spinal dorsal horn (L5-L6).Results Oxidative stress induced a significant increase in TDP-43 protein level in N2a cells,prompted mtDNA release through mPTP,markedly up-regulated the expression of cGAS and STING,and consequently impacted the viability of N2a cells (P<0.05).CsA treatment inhibited mPTP channel opening and thus effectively blocked mtDNA release (P<0.05),down-regulated TDP-43 and thus significantly reduced mtDNA release,suppressed the expression of cGAS and STING,and finally restored the proliferation ability of N2a cells (P<0.05).The mechanical and thermal pain thresholds exhibited a significant decrease since 5 d after CCI,which then persisted until 21 d (P<0.05).The expression of TDP-43 in spinal cord dorsal horn neurons was increased in the mice in 21 d after CCI (P<0.05),and intrathecal injection of siRNA inhibited TDP-43 expression and effectively increased the mechanical and thermal pain thresholds in the CCI mice (P<0.05).Conclusion Oxidative stress induces an up-regulation in TDP-43 protein in neurons,which stimulates the release of mtDNA into the cytoplasm through mPTP,and subsequently activates the cGAS/STING pathway,and finally,results in neuronal injury and pain sensitization in CCI mice.

Objective To investigate the effects of damaged nerve-derived mitochondrial DNA (mtDNA)on GRP75 protein expression,mitochondrial Ca2+level and apoptosis in human glioblastoma cell line U-87MG (U87)cells,and its mechanism of inducing pain sensitization in mice.Methods Chronic constriction injury (CCI) of the sciatic nerve was used to establish a mouse model of neuropathic pain (NeP).A total of 20 male C57BL/6 mice (6～8 weeks old,weighing 20～30 g)were randomly divided into sham group,and CCI-7,-14 and CCI-21 d groups.Paw withdrawal mechanical threshold (PWMT)was measured,and the changes in mtDNA content in the spinal cord were detected with quantitative real-time PCR (qPCR).After mtDNA was extracted from human neuroblastoma cells (SH-SY5Y)treated with H2O2,U87 cells were treated with mtDNA at a dose of 0～1 ng/μL.CCK-8 assay was utilized to detect cell viability,and the appropriate concentration was selected according to the results.Then U87 cells were divided into:control group,mtDNA group,mtDNA+GRP75 inhibitor (MKT-0771 μg/mL)group,mtDNA+calcium chelator (BAPTA-AM10 μmol/L)group,and mtDNA+MKT-077+BAPTA-AM group.MKT-077 and BAPTA-AM were pre-treated in 2 h before mtDNA treatment,respectively.Western blotting was employed to assess the expression of glucose-regulated protein 75 (GRP75) protein,and endoplasmic reticulum-mitochondrial colocalization staining was conducted to observe the endoplasmic reticulum-mitochondrial junction.Calcium ion fluorescent probe was used to measure mitochondrial Ca2+levels.The oxidative stress and function of mitochondria were evaluated by reactive oxygen species (ROS)and mitochondrial membrane potential.PI fluorescent labeling was employed to examine apoptotic rate of U87 cells.Results Compared with the sham group,the cytochrome C oxidase I (CO1)and nicotinamide adenine dinucleotide dehydrogenase 1 (ND1),which were utilized to measure mtDNA content in the spinal cord of mice in the CCI-21 group,were increased (1.01±0.20 vs 2.22±0.26,P<0.05,1.00±0.12 vs 1.79±0.07,P<0.05).CCK-8 assay showed that mtDNA (1 ng/μL) inhibited U87 cell viability (P<0.01).mtDNA (0.2 ng/μL) up-regulated the expression of GRP75 protein (P<0.05),promoted endoplasmic reticulum-mitochondrial coupling,and consequently increased mitochondrial Ca2+level (109.4±62.6 vs 540.3±150.3,P<0.05)and production of ROS (P<0.05).After MKT-077 or/and BAPTA-AM treatment,the level of mitochondrial Ca2+was decreased,the mitochondrial membrane potential was improved,and the apoptotic rate of U87 cells was reduced by PI assays (mtDNA vs mtDNA+MKT-077:18.39±2.09 vs 13.22±1.42,P<0.05;mtDNA vs mtDNA+BAPTA-AM:18.39±2.09 vs 12.09±1.53,P<0.05;mtDNA vs mtDNA+MKT-077+BAPTA-AM:18.39±2.09 vs 11.65±2.09,P<0.05).Conclusion Damaged nerve-derived mtDNA can up-regulate the expression of GRP75,interfere with mitochondrial Ca2+level and exacerbate mitochondrial oxidative stress to induce apoptosis in U87 cells,which may be a novel mechanism involved in NeP formation.