In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

Objective:To investigate the efficacy and safety of laparoscopic partial nephrectomy in the treatment of renal tumors with renal score of 10.Methods:From February 2016 to March 2021, 23 patients who underwent laparoscopic partial nephrectomy in Peking University Third Hospital with renal tumors of R. E.N.A.L. score of 10 was studied retrospectively, including 16 cases of male and 7 cases of female, with 11 cases on the right side and 12 cases on the left side. The patients’ age was (55.0±16.4) years, and BMI was (25.4±3.6) kg/m 2. The maximum diameter of the tumor was (3.5±1.4)cm. Laparoscopic partial nephrectomy was performed after complete examination. The observation indexes included operation time, blocking time, complications, postoperative hospital stay and the trifecta (negative surgical margin, blocking time ≤25 minutes, and no perioperative complications). Results:All operations were successfully completed, only 4 cases were converted to open surgery. The median operation time was 153 min(99-346 min). The median blocking time was 27 min(14-60min). The median postoperative hospital stay was 6 d(4-11 d). Postoperative complications occurred in 7 cases(fever in 5 cases, intestinal obstruction in 1 case, postoperative blood transfusion and leg intermuscular venous thrombosis in 1 case). 9 cases (39.1%) achieved the trifecta. 19 cases who completed by laparoscopy, their operation time was 151 min(99-303 min), blocking time was 28 min(18-60 min), postoperative hospital stay was 6 d(4-11 d), fever occurred in 4 cases, and 6 cases achieved the trifecta (31.6%). The follow-up time was 3-62 months, with a median of 32 months, and there was no recurrence or metastasis.Conclusions:Laparoscopic partial nephrectomy is safe and effective in the treatment of renal tumors with renal score of 10.Although the tumor is highly complex, it also achieves the purpose of preserving nephron to the greatest extent. If technical conditions permit, laparoscopic partial nephrectomy could be considered for the treatment of highly complex renal tumors.

From September to November 2019, three patients with Hornet stings were admitted to hospital with acute anaphylaxis and various degrees of organ dysfunction. After hemoperfusion combined with continuous hemodialysis and hormone pulse therapy, 1 patient was successfully treated and 2 patients were not cured. Bee Stings can cause systemic allergic reactions and toxic reactions. In severe cases, acute anaphylaxis, rhabdomyolysis, intravascular hemolysis, abnormal coagulation, and acute liver and kidney injury may occur, myocardial damage and other multi-organ function damage or even failure, is a clinical acute and critical illness, mortality is higher. Through the analysis of the diagnosis and treatment process of these 3 cases, the experience is summarized: the Bee sting should be treated as soon as possible, the early prevention and treatment of multiple organ dysfunction, the choice of accurate blood purification and comprehensive treatment, can effectively improve the prognosis, increase the success rate of treatment.

In order to meet the needs of detection of poisoning-inducing pesticides occurring in poisoning emergency events, this article introduces and discusses the characteristics, scope of application, and advantages and disadvantages of two types of detection technologies: laboratory detection and on-site rapid detection. The sample pre-processing technology suitable for on-site detection is also elaborated.

From September to November 2019, three patients with Hornet stings were admitted to hospital with acute anaphylaxis and various degrees of organ dysfunction. After hemoperfusion combined with continuous hemodialysis and hormone pulse therapy, 1 patient was successfully treated and 2 patients were not cured. Bee Stings can cause systemic allergic reactions and toxic reactions. In severe cases, acute anaphylaxis, rhabdomyolysis, intravascular hemolysis, abnormal coagulation, and acute liver and kidney injury may occur, myocardial damage and other multi-organ function damage or even failure, is a clinical acute and critical illness, mortality is higher. Through the analysis of the diagnosis and treatment process of these 3 cases, the experience is summarized: the Bee sting should be treated as soon as possible, the early prevention and treatment of multiple organ dysfunction, the choice of accurate blood purification and comprehensive treatment, can effectively improve the prognosis, increase the success rate of treatment.

Objective To investigate the target achievement of serum trough concentration of vancomycin in elderly patients routinely treated with vancomycin,and to analyze the influencing factors for vancomycin-associated acute kidney injury(VA-AKI).Methods A single-center retrospective study was conducted by collecting clinical data of elderly inpatients from January 2016 to July 2017 who received intravenous vancomycin therapy and serum vancomycin trough concentration test.Logistic regression was used to analyze the risk factors for VA-AKI.Results A total of 141 patients were enrolled,including 74 males (52.5 ％) and 67 females (47.5 ％).The median (interquartile range)age was 77.0(13.5) years old.Patients with serum vancomycin trough concentrations within 10～ 20 mg/L accounted for 48.9 ％ (69 cases),while those lower than the target value accounted for 23.4 ％ (33 cases),and those higher than the target value accounted for 27.7％ (39 cases).Patients were divided into three groups according to the vancomycin serum trough concentration:＜10 mg/L group,10～20 mg/L group,and ＞20 mg/L group.There were statistically significant differences among the three groups in median(interquartile range) age[74.0 (14.0) years old,76.0 (11.5) years old vs.80.0 (14.0) years old,H =9.506,P =0.009] and the median (interquartile range) vancomycin daily dose [1.5(0.5) g/d,1.5 (0.8) g/d vs.1.5 (0.5) g/d,H =6.131,P =0.047].VA-AKI occurred in 23 patients(16.3 ％).Logistic regression analysis showed that the baseline serum creatinine levels (OR =1.022,95 ％CI:1.001 ～ 1.042,P =0.035)and vancomycin trough concentration(OR =1.058,95 ％CI:1.011～1.106,P=0.015)were influencing factors for VA-AKI.Conclusions The elderly patients with infection who received clinical vancomycin therapy have a low target achievement rate of serum trough concentration.Baseline serum creatinine level and serum vancomycin trough concentration are influencing factors for VA-AKI.

Hypothyroidism is a common adverse reaction in clinical multi-target tyrosine kinase inhibitor (TKI) and may be used as a predictor of efficacy of TKI drugs.Studies show that hypothyroidism is significantly associated with good prognosis in patients with renal cell carcinoma treated with multi-target TKI,which may be related to inhibition of vascular endothelial growth factor receptor pathway,potential off-target effects and inhibition of cell proliferation.Whereas in the patients with hepatocellular carcinoma who received multi-target TKI therapy,hypothyroidism is an indicator of poor prognosis,which is related to the T3/TR pathway regulating liver cancer growth and invasion.The predictive function and mechanism of thyroid hormone levels in different tumor patients receiving multi-target TKI drugs are different,and further research is still needed.

Objective: To investigate the clinical value of multimodal navigation-based virtual reality (MNVR) in the needle biopsy of intracranial eloquent lesions. Methods: From January 2016 to January 2017, 20 patients with intracranial deep-seated lesions involving eloquent brain areas underwent MNVR-aided needle biopsy at Department of Neurosurgery, People′s Liberation Army General Hospital. Preoperatively, MNVR was used to propose and revise the biopsy planning. Intraoperatively, navigation helped trajectory avoid the eloquent structures. Intraoperative MRI (iMRI) was performed to prove the biopsy accuracy and detect the intraoperative complications. Perioperative neurological status, iMRI findings, intraoprative complications, surgical outcome and pathological diagnosis were recorded. Wilcoxon rank-sum test was conducted to compare the preoperative and postoperative neurological scores. Results: MNVR helped revised 45%(9/20) initial biopsy trajectories, which would probably injury the nearby eloquent structures. Navigation helped biopsy trajectories spare the eloquent structures during the operation. No statistical difference was found between postoperative and preoperative neurological status, despite all the lesions were adjacent to eloquent areas. Additionally, 20 patients totally received 21 iMRI scanning. iMRI helped revise incorrect biopsy site in one case and detected intraoperative hemorrhage in another case, both of cases were treated immediately and effectively. No MNVR related adverse events and complications occurred. Conclusions MNVR-aided needle biopsy of intracranial eloquent lesions is a safe, novel and efficient biopsy modality. This technique is helpful to reduce the incidence of surgery related neurological deficits.

Objective: To explore the clinical useness of intraoperative functional neuronavigation and fluorescent indocyanine green(ICG) angiography as well as electrophysiological evaluation during microsurgical resection of cerebral arteriovenous malformations (AVM). Methods: A series of 42 consecutive cases with AVM underwent microsurgery by intraoperative functional neuronavigation at Department of Neurosurgery of People′s Liberation Army General Hospital from January 2009 to February 2015 were retrospectively analyzed. Of the 42 patients, 29 were males and 13 were females aging from 4 to 62 years (mean age 32.6 years). Preoperative assessment included functional magnetic resonance imaging and diffusion tensor imaging to identify the relationship between lesions and eloquent areas. The results of images were integrated into three-dimensional datasets to achieve intraoperative microscopic-based functional neuronavigation during AVM resection. Operations involved in motor areas and corticospinal tract were performed under continuous electrophysiological monitoring. ICG angiography was performed at pre-dissection, post-clipping of the feeders, and post-resection of the nidus. FLOW 800 software presented a color map and ICG intensity-time curve to demostrate the vascular architecture. Postoperative digital subtraction angiography was re-examined routinely to evaluate the extent of resection. Clinical outcomes were evaluated with the modified Rankin Scale. Results: All patients underwent surgery under intraoperative navigation. Of the 42 patients, total resection was achieved in 36 cases (85.7%, 36/42) including 14 cases of AVM in eloquent areas. A total of 40 ICG angiographies were successfully performed among 11 patients. Average number of ICG injections per operation was 3.6 (ranging from 3 to 6). Feeders were visualized in 10 patients and drainers were visualized in 9 cases. The post-surgical follow-up period varied from 3 months to 70 months (mean 22.5 months). 83.8% of the patients returned to normal work and life during the followed-up period. Conclusion Combining intraoperative neuronavigation and electrophysiological monitoring, as well as fluorescent ICG angiography contribute to microsurgical resection of cerebral AVM effectively in selecting suitable patients, further avoiding neurologic compromise as well.

OBJECTIVETo explore the effects of direct current electric fields on directional migration and arrangement of dermal fibroblasts in neonatal BALB/c mice and the related mechanisms.

METHODSTwelve neonatal BALB/c mice were divided into 4 batches. The skin on the back of 3 neonatal mice in each batch was obtained to culture fibroblasts. Fibroblasts of the second passage were inoculated in 27 square cover slips with the concentration of 5 × 10(4) cells per mL. (1) Experiment 1. Six square cover slips inoculated with fibroblasts of the second passage were divided into electric field group (EF) and sham electric field group (SEF), with 3 cover slips in each group. The cover slips were put in live cell imaging workstation. The cells in group EF was treated with electric power with EF intensity of 200 mV/mm, while simulating process without actual power was given to SEF group (the same below) for 6 h. Cell proliferation rate was subsequently counted. (2) Experiment 2. Six cover slips were divided and underwent the same processes as in experiment 1. Cell movement locus within EF hour (EFH) 6, direction change of cell migration at EFH 0 (immediately), 1, 2, 3, 4, 5, and 6 which was denoted as cos(α), cell migration velocity within EFH 6, direction change of long axis of cell within EFH 6, and direction change of cell arrangement at EFH 0, 1, 2, 3, 4, 5, and 6 which was denoted as polarity value cos[2(θ-90)] were observed under live cell imaging workstation. After EFH 6, the morphological changes in microtubules and microfilaments were observed with immunofluorescent staining. (3) Experiment 3. Six cover slips were divided into cytochalasin D group (treated with 1 μmol/L cytochalasin D for 10 min) and colchicine group (treated with 5 μmol/L colchicine for 10 min), with 3 cover slips in each group. The morphological changes in microfilaments and microtubules were observed with the same method as in experiment 2. (4) Experiment 4. Nine cover slips were divided into control group (no reagent was added), cytochalasin D group and colchicine group (added with the same reagents as in experiment 3), with 3 cover slips in each group. Cells in the 3 groups were exposed to an EF of 200 mV/mm for 6 h. Cell movement locus within EFH 6, cell migration velocity within EFH 6, cell polarity values at EFH 0, 3, and 6, and morphological changes of cells at EFH 0 and 6 were observed. Data were processed with independent samples t-test, one-way analysis of variance, and LSD test.

RESULTS(1) There was no statistically significant difference in cell proliferation rate in group EF and group SEF (t=-0.24, P﹥0.05). (2) Within EFH 6, cells in group EF migrated towards the anode of EF, while cells in group SEF moved randomly. At EFH 0, the values of cos(α) of cells in the 2 groups were both 0. The absolute value of cos(α) of cells in group EF (-0.57 ± 0.06) was significantly higher than that in group SEF (0.13 ± 0.09, t=6.68, P<0.01) at EFH 1, and it was still higher than that in group SEF from EFH 2 to 6 (with t values from 5.33 to 6.83, P values below 0.01). Within EFH 6, migration velocity of cells in group EF was (0.308 ± 0.019) μm/min, which was significantly higher than that in group SEF [(0.228 ± 0.021) μm/min, t=-2.76, P<0.01]. Within EFH 6, long axis of cells in group EF was perpendicular to the direction of EF, while arrangement of cells in group SEF was irregular. Cell polarity values in group EF were significantly higher than that in group SEF from EFH 2 to 6 (with t values from -7.52 to -0.90, P values below 0.01). At EFH 6, the morphology of microfilaments and microtubules of cells in EF group was similar to that in SEF group. (3) The fluorescent intensity of microfilaments of cells in cytochalasin D group became weakened, and the filamentary structure became fuzzy. The microtubules of cells in colchicine group became fuzzy with low fluorescent intensity. (4) Within EFH 6, cells in control group migrated towards the anode of EF, while cells in cytochalasin D group and colchicine group moved randomly. Within EFH 6, there was statistically significant difference in migration velocity of cells in the 3 groups (F=6.36, P<0.01). Migration velocity of cells in cytochalasin D group and colchicine group was significantly slower than that in control group (P<0.05 or P<0.01). At EFH 0, 3, and 6, cell polarity values in the 3 groups were close (with F values from 0.99 to 1.51, P values above 0.05). At EFH 0, cells in control group were spindle; cells in cytochalasin D group were polygonal or in irregular shapes; cells in colchicine group were serrated circle or oval. At EFH 6, no morphological change was observed in cells in control group; cells in cytochalasin D group were spindle with split ends on both ends; cells in colchicine group were serrated oval.

CONCLUSIONSThe physiologic strength of exogenous direct current EF can induce directional migration and alignment of dermal fibroblasts in neonatal BALB/c mice. Microfilaments and microtubules are necessary skeleton structure for cell directional migration induced by EF, while they are not necessary for cell directional arrangement induced by EF.

Animals ; Cell Movement ; Cells, Cultured ; Electricity ; Fibroblasts ; cytology ; Mice ; Mice, Inbred BALB C ; Microtubules ; Skin ; cytology