The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To observe the effects of tuina of"three methods and three acupoints"on skeletal muscle α-actin,myostatin(MSTN)and atrophy gene 1(Atrogin1)expression of sciatic nerve injury(SNI)rats;To explore the mechanism of tuina therapy on motor dysfunction.Methods Male SD rats were randomly divided into blank group,sham-operation group,model group and tuina group,with 9 rats in each group.SNI model was established by clamp method in rats of the model group and tuina group.The sciatic nerve was exposed without clamping in rats of the sham-operation group,the blank group was not intervened.7 days after the operation,the intelligent tuina manipulation simulator was used to simulate the point method,dial method and knead method,which were applied to the"Yinmen"(BL37),"Chengshan"(BL57)and"Yanglingquan"(GB34)of rats in the tuina group,once a day,for 20 times.The rats in the sham-operation group and the model group were only grasped and restrained.Rats in the blank group did not receive any intervention.The hind limb muscle strength were evaluated by inclined plate test before modeling,after 10 interventions and 20 interventions.After the intervention,the rats were euthanized.The expressions of α-actin in gastrocnemius muscle tissue were detected by immunofluorescence staining,the expressions of MSTN,Atrogin1 mRNA and protein in gastrocnemius muscle tissue were detected by RT-PCR and Western blot.Results Compared with the blank group and sham-operation group,the model group showed a decrease in hind limb muscle strength(P<0.01),a significant decrease in α-actin expression in gastrocnemius muscle tissue(P<0.01),and a significant increase in MSTN,Atrogen1 mRNA and protein expression(P<0.05,P<0.01).Compared with the model group,the hind limb muscle strength in tuina group significantly increased(P<0.01),the expressions of α-actin significantly increased(P<0.01),and the expressions of MSTN,Atrogin1 mRNA and protein significantly decreased(P<0.05,P<0.01).Conclusion"Three methods and three acupoints"tuina can improve hind limb muscle strength and restore motor function of SNI rats,which is related to the down-regulation of MSTN and Atrogin1 as well as increasing the expression of α-actin in gastrocnemius muscles.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To analyze the influence factors of urinary tract infection after transurethral bipolar plasma enucleation of the prostate (TUPEP) in patients with benign prostatic hyperplasia(BPH), and the early predictive value of serum inflammatory indicators for postoperative urinary tract infection.Methods:A total of 300 patients with BPH who received TUPEP treatment in the Department of Urology, Kailuan General Hospital from January 2021 to August 2023 were selected, according to whether they had urinary tract infections after the operation, they were divided into infection group ( n=117) and non-infection group ( n=183). The clinical data of the two groups were collected, and the serum inflammatory indexes of the two groups were recorded within 24 hours after the operation, including white blood cell count (WBC), neutrophil granulocyte (NE%), high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), procalcitonin (PCT), heparin-binding protein (HBP), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and serum ferritin (SF). The differences of clinical data and serum inflammatory indexes between the two groups were analyzed. The measurement data of normal distribution were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for inter-group comparisons. The measurement data of non- normal distribution were represented by median (interquartile range) [ M ( Q1, Q3)], and the Mann-Whitney U test was used for inter-group comparison. The count data were expressed as cases and percentage, and inter-group comparisons were conducted using the Chi-test. Multivariate Logistic regression analysis was used to explored the influencing factors of urinary tract infections in BPH patients after TUPEP surgery. The receiver operating characteristic (ROC) curve was plotted using GraphPad Prism 8.0.1 medical plotting softwar to evaluate the predictive value of serum inflammatory markers and combined detection of multiple markers for early postoperative urinary tract infections. Results:The duration of disease, history of diabetes, international prostate symptom score (IPSS), prostate volume, preoperative serum prostate-specific antigen (PSA) level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time, and hospitalization time in the infection group were higher than those in the non-infection group ( P<0.05). The preoperative 25-hydroxyvitamin D (25OHD) level and maximum urinary flow rate were lower in the infection group than those in the non- infection group ( P<0.05). Multivariate Logistic regression analysis showed that the course of the disease, history of diabetes, IPSS score, prostate volume, preoperative PSA level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time was positively correlated with urinary tract infection after TUPEP ( B=0.660, 0.242, 0.164, 0.125, 0.230, 0.066, 0.382, 0.022, 0.436, P<0.01), and preoperative 25OHD level and preoperative maximum urinary flow rate were negatively correlated with urinary tract infection after TUPEP ( B=-0.216, -0.372, P<0.01). The levels of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in the infection group were higher than those in the non-infection group ( P<0.001). The ROC curve analysis showed that the area under the curve (AUC) of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in early predicting urinary tract infection after TUPEP in BPH patients were 0.697, 0.775, 0.902, 0.873, 0.884, 0.904, 0.917, 0.823, 0.906, 0.852, 0.807, 0.787. The AUC of the combined detection of multiple serum inflammatory markers was 0.972, the sensitivity and specificity were 93.18% and 96.63%, and the sensitivity and specificity of the combined detection of multiple serum inflammatory markers were higher than those of separate detection. Conclusion:The course of BPH, whether to combine history of diabetes, preoperative IPSS score, prostate volume, preoperative PSA level, preoperative 25OHD level, preoperative maximum urinary flow rate, operation time, intraoperative blood loss, and postoperative catheter indwelling time are influencing factors of urinary tract infection after TUPEP, hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF had certain value in the early prediction of urinary tract infection after TUPEP in patients with BPH, the combination of multiple indicators can improve the predictive value of early urinary tract infection.

To describe the incidence and mortality of adult head and neck cancer (HNC) in different regions worldwide and their temporal trends.

Objective: To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI). Methods: Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF. Results: Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001). Conclusion TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To analyze early improvements in clinical indicators among patients with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), and hypertension (HT) participating in the Chronic Disease Co-Care (CDCC) Pilot Scheme in the Hong Kong Special Administrative Region of the People′s Republic of China (HKSAR). Methods:This longitudinal study enrolled participants with pre-DM, T2DM, and HT who participated in the CDCC Pilot Scheme between November 2023 and May 2024. Baseline clinical data was collected. All participants were managed followed standardized protocols: family doctors issued prescriptions in accordance with the Hong Kong Reference Framework by the Health Bureau of the Government of the HKSAR, District Health Centre (DHC) and DHC Express provided health education, and personalized counseling by allied health professionals (nurses, optometrists, and dietitians). During the screening phase, screening costs, including consultations and related laboratory investigations, were fully covered by the Government of the HKSAR, while partial subsidies were available during the treatment phase. Participants were followed for 6 months. Primary outcomes were glycated hemoglobin A1c (HbA1c) for pre-DM and T2DM, and blood pressure for HT. Secondary outcomes included body mass index (BMI), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the Framingham model-based 10-year cardiovascular risk score. Changes in clinical indicators from baseline to 6 months were analyzed using a linear mixed model, with subgroup analyses by age, sex, and baseline Framingham 10-year cardiovascular disease risk score. Results:A total of 3 910 participants were included in the study, comprising 903 (23.1%) with pre-DM, 478 (12.2%) with T2DM, and 2 529 (64.7%) with HT. Pre-DM participants had an age of (61.4±7.0) years with 641 (71.0%) females; T2DM participants had an age of (60.4±7.4) years with 247 (51.7%) females; HT participants had an age of (60.8±7.9) years with 1 237 (48.9%) females. At 6 months, HbA1c levels declined in the pre-DM and T2DM groups by -0.09% (95% CI:-0.10%--0.07%) and -1.06% (95% CI:-1.21%--0.91%), respectively. In the HT group, systolic blood pressure decreased by 15.3 mmHg (1 mmHg=0.133 kPa) (95% CI:-16.0--14.6 mmHg) and diastolic blood pressure by 8.6 mmHg (95% CI:-9.0--8.1 mmHg). BMI decreased in the three groups, with the largest reduction in the T2DM group (-1.04 kg/m 2, 95% CI:-1.22--0.86 kg/m 2). TC, TG, and LDL-C levels decreased in the three groups (all P<0.05). Subgroup analysis revealed that among HT participants, individuals with a baseline Framingham 10-year cardiovascular disease risk of ≥20% experienced greater reductions in blood pressure compared to those with a risk <20% ( P<0.05). Additionally, male participants demonstrated significantly lower diastolic blood pressure than female participants ( P<0.05). Among participants with T2DM, males exhibited greater reductions in HbA1c levels than females, and participants aged 45-64 years showed significantly lower HbA1c levels compared to those aged 65 years and older (both P<0.05). Conclusions:In the early phase of the CDCC Pilot Scheme, glycemic, blood pressure, lipid, and BMI indicators improved among patients with pre-DM, T2DM, and HT. These effects were particularly pronounced in males and in individuals younger than 65 years of age.

Objectives:To systemically evaluate the efficacy and safety of His-Purkinje conduction system pacing(HPCSP,including His bundle pacing[HBP]and left bundle branch area pacing[LBBAP])combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure.Methods:The PubMed,Cochrane Library,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,and Yiigle were searched for studies on HPCSP combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure since the established until July 31,2024.Meta-analysis was performed using RevMan 5.4 and Stata 15.1.Results:A total of 13 studies were included with 1 071 patients,the success rate of HPCSP combined with atrioventricular node ablation was 93.1%.The meta-analysis results revealed that,in terms of effectiveness outcomes,compared with baseline,left ventricular end-diastolic diameter(mean difference[MD]=-3.11,95%CI:-4.16 to-2.06,P<0.000 01)was significantly reduced,New York Heart Association(NYHA)cardiac function classification(MD=-1.36,95%CI:-1.48 to-1.24,P<0.000 01)was significantly decreased,and left ventricular ejection fraction(MD=9.86,95%CI:7.02 to 12.69,P<0.000 01)was significantly increased during follow-up.The pacing QRS duration was prolonged from baseline after atrioventricular node ablation(MD=7.83,95%CI:2.79 to 12.87,P=0.002);In terms of safety outcomes,HPCSP pacing thresholds remained stable(MD=0.07,95%CI:-0.01 to 0.15,P=0.11)and impedance was decreased(MD=-78.84,95%CI:-120.21 to-37.47,P=0.000 2)during operation and follow-up.The complication rate was 7.9%,the heart failure rehospitalization rate was 4.5%and the mortality rate was 5.8%.Compared with biventricular pacing(BVP),HPCSP was correlated with shorter pacing QRS duration(MD=-39.08,95%CI:-62.35 to-15.80,P=0.001)and higher left ventricular ejection fraction(MD=4.38,95%CI:0.37 to 8.40,P=0.03),there was no significant difference in left ventricular end-diastolic diameter(MD=-9.11,95%CI:-19.93 to 1.72,P=0.100).During follow-up,LBBAP exhibited a lower pacing threshold than HBP(MD=0.61,95%CI:0.23 to 1.00,P=0.002);Endpoint event rates were similar between HBP and LBBP(RR=1.47,95%CI:0.83 to 2.60,P=0.190).Conclusions:Results of this meta-analysis demonstrate that HPCSP combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure is effective and safe.HPCSP is associated with better ventricular electro-mechanical synchronization and cardiac function compared with BVP,and LBBAP pacing parameters are superior to HBP.

Objectives:To systemically evaluate the efficacy and safety of His-Purkinje conduction system pacing(HPCSP,including His bundle pacing[HBP]and left bundle branch area pacing[LBBAP])combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure.Methods:The PubMed,Cochrane Library,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,and Yiigle were searched for studies on HPCSP combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure since the established until July 31,2024.Meta-analysis was performed using RevMan 5.4 and Stata 15.1.Results:A total of 13 studies were included with 1 071 patients,the success rate of HPCSP combined with atrioventricular node ablation was 93.1%.The meta-analysis results revealed that,in terms of effectiveness outcomes,compared with baseline,left ventricular end-diastolic diameter(mean difference[MD]=-3.11,95%CI:-4.16 to-2.06,P<0.000 01)was significantly reduced,New York Heart Association(NYHA)cardiac function classification(MD=-1.36,95%CI:-1.48 to-1.24,P<0.000 01)was significantly decreased,and left ventricular ejection fraction(MD=9.86,95%CI:7.02 to 12.69,P<0.000 01)was significantly increased during follow-up.The pacing QRS duration was prolonged from baseline after atrioventricular node ablation(MD=7.83,95%CI:2.79 to 12.87,P=0.002);In terms of safety outcomes,HPCSP pacing thresholds remained stable(MD=0.07,95%CI:-0.01 to 0.15,P=0.11)and impedance was decreased(MD=-78.84,95%CI:-120.21 to-37.47,P=0.000 2)during operation and follow-up.The complication rate was 7.9%,the heart failure rehospitalization rate was 4.5%and the mortality rate was 5.8%.Compared with biventricular pacing(BVP),HPCSP was correlated with shorter pacing QRS duration(MD=-39.08,95%CI:-62.35 to-15.80,P=0.001)and higher left ventricular ejection fraction(MD=4.38,95%CI:0.37 to 8.40,P=0.03),there was no significant difference in left ventricular end-diastolic diameter(MD=-9.11,95%CI:-19.93 to 1.72,P=0.100).During follow-up,LBBAP exhibited a lower pacing threshold than HBP(MD=0.61,95%CI:0.23 to 1.00,P=0.002);Endpoint event rates were similar between HBP and LBBP(RR=1.47,95%CI:0.83 to 2.60,P=0.190).Conclusions:Results of this meta-analysis demonstrate that HPCSP combined with atrioventricular node ablation for the treatment of atrial fibrillation combined with heart failure is effective and safe.HPCSP is associated with better ventricular electro-mechanical synchronization and cardiac function compared with BVP,and LBBAP pacing parameters are superior to HBP.