Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

The application of immune checkpoint inhibitors has changed the treatment paradigm for advanced non-small cell lung cancer(NSCLC).However,interruption of immune checkpoint inhibitor therapy due to intolerable adverse effects or due to disease progression has become a problematic issue in the treatment of advanced NSCLC.Whether immune checkpoint inhibitors rechallenge therapy is possible after interruption of immune checkpoint inhibitor therapy has been proposed and remains controversial.This article summarizes the types of immune checkpoint inhibitor rechallenge and therapeutic strategies for advanced NSCLC,and finds that patients with NSCLC who have interrupted their immunotherapy due to immune-related adverse events and clinical decision-making can still achieve a better favorable clinical outcomes.It is hypothesized that immune checkpoint inhibitor rechallenge for NSCLC after drug resistance is an alternative salvage therapy.

The application of immune checkpoint inhibitors has changed the treatment paradigm for advanced non-small cell lung cancer(NSCLC).However,interruption of immune checkpoint inhibitor therapy due to intolerable adverse effects or due to disease progression has become a problematic issue in the treatment of advanced NSCLC.Whether immune checkpoint inhibitors rechallenge therapy is possible after interruption of immune checkpoint inhibitor therapy has been proposed and remains controversial.This article summarizes the types of immune checkpoint inhibitor rechallenge and therapeutic strategies for advanced NSCLC,and finds that patients with NSCLC who have interrupted their immunotherapy due to immune-related adverse events and clinical decision-making can still achieve a better favorable clinical outcomes.It is hypothesized that immune checkpoint inhibitor rechallenge for NSCLC after drug resistance is an alternative salvage therapy.

Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.

Objective:To investigate whether myocardial inflammation and apoptosis are involved in right ventricular dysfunction (RVD) induced by injurious mechanical ventilation with high tidal volume (VT) in rats.Methods:Total 30 adult male SD rats were randomly divided into the control group (CON group), the low VT ventilation group (LVT group) and the injurious mechanical ventilation group (HVT group), with 10 rats in each group. The CON group was maintained spontaneous breathing, the LVT group and HVT group were ventilated with different VT 6 mL/kg and 20 mL/kg for 4 hours, respectively. The right jugular vein and the left carotid artery were catheterized and connected with the PowerLab biological signal acquisition and analysis system to record heart rate (HR), mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (+dp/dt max). Echocardiography was performed to measure left ventricular end-diastolic diameter (LVEDd), right ventricular end-diastolic diameter (RVEDd), tricuspid annulus plane systolic migration (TAPSE) and myocardial performance index (MPI). The rats were sacrified by cervical dislocation. Specimens of right ventricle tissues were taken for hematoxylin-eosin (HE) staining, and morphological changes of right ventricle tissues were observed under light microscope. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3, apoptosis-related proteins Bax and Bcl-2.Results:HR, MAP, +dp/dt max gradually decreased, while RVSP gradually increased in different group with the increase of VT ventilation. There was no significant difference between the CON group and LVT group. However, there was a statistically significant difference with respect to these index in HVT group as compared to CON group and LVT group [HR (bpm): 397.6±5.7 vs. 433.0±4.8, 441.6±7.8; MAP (mmHg, 1 mmHg≈0.133 kPa): 102.0±2.4 vs. 108.5±2.2, 110.6±2.1; +dp/dt max (mmHg/s): 2 357.65±62.80 vs. 2 661.27±55.62, 2 679.43±75.13; RVSP (mmHg): 28.8±1.0 vs. 22.6±10.8, 21.9±0.4; all P < 0.05]. Echocardiography findings showed that RVEDd/LVEDd and MPI gradually increased, TAPSE gradually decreased in different group with the increase of VT ventilation. There was no significant difference between the LVT group and CON group. However, there was a statistically significant difference with respect to these indexes in HVT group as compared to the CON group and LVT group [RVEDd/LVEDd: 0.36±0.02 vs. 0.26±0.01, 0.23±0.02; MPI: 1.23±0.03 vs. 0.84±0.04, 0.86±0.03; TAPSE (mm): 1.65±0.03 vs. 1.88±0.02, 1.91±0.04; all P < 0.05]. Histopathological observation of the right ventricle tissue showed that myocardial cells of the rats in the CON group were orderly arranged and uniformed in size. In the LVT group, there was a small amount of inflammatory cell infiltration in the myocardial interstitium, while in the HVT group, the myocardial cell arrangement was obviously disordered, the structure was obviously damaged, and more inflammatory cell infiltration was found. RT-PCR and Western blotting analysis showed that the mRNA and protein expressions of IL-6, TNF-α, caspase-3 and Bax in HVT group were significantly higher than those in the LVT group and CON group [mRNA expression (2 -ΔΔCt): IL-6 were 1.97±0.07 vs. 1.09±0.02, 1.02±0.03, TNF-α were 1.69±0.10 vs. 1.10±0.03, 1.05±0.04, caspase-3 were 1.82±0.09 vs. 1.08±0.02, 1.06±0.03, Bax were 2.19±0.14 vs. 1.07±0.03, 1.04±0.03; protein expression (gray value): IL-6 were 0.64±0.02 vs. 0.38±0.03, 0.31±0.04, TNF-α were 0.50±0.04 vs. 0.16±0.01, 0.15±0.01, caspase-3 were 0.58±0.02 vs. 0.29±0.01, 0.25±0.02, Bax were 0.50±0.03 vs. 0.21±0.01, 0.26±0.02; all P < 0.05], and the mRNA and protein expressions of Bcl-2 in the HVT group were lower than those in the LVT group and CON group [mRNA expression (2 -ΔΔCt): 1.23±0.05 vs. 1.43±0.05, 1.50±0.08; protein expression (gray value): 0.42±0.02 vs. 0.62±0.03, 0.65±0.03, all P < 0.05]. Conclusion:Myocardial inflammation and apoptosis may be involved in RVD induced by injurious mechanical ventilation.

Objective    To propose a path planning method for precise robot-assisted bronchial intervention. Methods    In the MuJoCo dynamic simulation environment, a simulation model and a simulated bronchus model which could accurately represent the motion process of the robot were built. Based on the Informed RRT* algorithm, the known spatial information was used to improve the path planning method and the motion characteristics of the robot were simulated to verify the ability of the robot algorithm to reach the target position. Results    In the dynamic simulation environment, the robot could move as required, and could explore the target point of the planning task in a short time, and the position accuracy was improved by more than 50% compared with the existing electromagnetic navigation and other methods. Conclusion    The established simulation model can restore the motion of the robot, and the robot has the ability to move in the bronchial environment. The proposed method can precisely control the simulated robot to enter the more peripheral airway position. It has the advantages of accuracy and faster speed than traditional manual interventional surgery, and can be used for the human-machine coordinated control task of robot-assisted bronchoscopy.

Objective:To explore the treatments and outcomes of heart and kidney transplantation(HKTx)and summarize its management experiences.Methods:From October 2016 to October 2020, clinical data, treatment strategies and prognosis of 11 patients received HKTx were analyzed retrospectively.In 11HKTx cases, the ratio of male-to-female was 10∶1, the age(50.6±12.9)years and the preoperative body mass index(26.72±3.29)kg/m 2.The preoperative cardiac function was class Ⅳ and the preoperative left ventricular ejection fraction(29.40±4.48)%.All patients were in uremic state pre-operation and underwent regular dialysis.The mean duration of dialysis was 2.5(0.5-7.0)years, preoperative creatinine 753.5(434-1144)μmol/L and preoperative predictive glomerular filtration rate 5.59(3.93-17.23)ml/(min preop 2). Non-staged transplant was performed and donor heart and kidney were from the same donor.The median time of cold cardiac ischemia 2.75(2.5, 4.0)hours, the median time of cold renal ischemia 9(8.5, 15.0)hours and the median time from the end of heart transplantation to the beginning of kidney transplantation 2(1.0, 3.5)hours.The immunosuppressive regimen was a combination of tacrolimus, mycophenolate mofetil and methylprednisolone. Results:Normal cardiac function and renal function normalized in 9 cases.At Month 6 post-operation, the postoperative left ventricular ejection fraction was(57.55±2.51)%, creatinine 107.7(85-132)μmol/L and urine volume in 24h 1988(1800-2200)ml.The long-term survival time was 6-62 months.No such complications as infection or rejection occurred in 9 patients.The cardiac function was class Ⅰ at Month 6 post-operation.One patient died from pulmonary mucor infection at Month 4 post-operation.Another death was due to gastrointestinal fungal infection at Month 1 after HKTx.Conclusions:HKTx is an effective treatment for end-stage heart disease with renal failure.

Oridonin is one of the main anti-tumor active ingredients of Rabdosiae Rubescentis Herba. In the development process of a variety of malignant tumors, such as liver cancer, breast cancer, cervical cancer, pancreatic cancer, lung cancer, gastric cancer, esophageal cancer, colon cancer, etc, it has a significant inhibitory effect. Oridonin plays the rold of anti-tumor effect mainly by inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and migration, inducing tumor cell autophagy, reducing telomerase activity and reversing the drug resistance of the tumor cell.

Objective:To investigate the effects of theta burst stimulation(TBS)mode repeated transcranial magnetic stimulation (r-TMS) in the left prefrontal on negative symptoms and cognitive function in the elderly chronic schizophrenic patients.Methods:Totally 48 patients with stable chronic senile schizophrenia (24 cases in r-TMS treatment group and 24 cases in r-TMS pseudo stimulation control group) were selected. The treatment group was given the TBS mode r-TMS performed in the left dorsolateral prefrontal cortex. The control group was given pseudo stimulation at the same site. Before and after treatment, the brief psychiatric rating scale(BPRS), scale for assessment of negative symptoms(SANS), and positive and negative syndrome scale(PANSS)were used to assess mental symptoms, while Mattis-dementia rating scale(MDRS-2)and social adaptation functioning evaluation(SAFE)were used to assess cognitive function and social function. SPSS 20.0 was used for statistical analysis.Comparisons of the differences between inter groups and intra groups were conducted by independent sample t test and paired t-test. Results:(1)There were significant differences in the total score of PANSS scale((60.17±3.73), (56.67±3.12)), the negative symptom subscale score of PANSS((20.88±2.94), (17.96±2.33)) and the score of SANS((30.67±1.66), (30.25±1.45)) before and after treatment in the treatment group (all P<0.05). The D-value before and after treatment in the scores of BPRS ( t=3.513, P=0.001), PANSS ( t=6.048, P<0.01), negative symptom subscale ( t=6.610, P<0.01) and SANS ( t=8.239, P<0.01) were significantly different between the two groups. (2)There were significant differences in the scores of MDRS-2 and its sub scales before and after treatment in the treatment group (all P<0.05). The D-value before and after treatment in the scores of MDRS-2 ( t=6.216, P<0.01), attention ( t=4.596, P<0.01), start/maintain ( t=6.424, P<0.01), concept formation ( t=3.974, P<0.01), construction( t=2.194, P=0.033) and memory ( t=3.162, P=0.003) were significantly different between the two groups.(3)There was no significant difference in the SAFE score between the treatment group and the control group before and after treatment ( t=0.138, 0.142, both P>0.05). Conclusion:TBS can improve the negative symptoms and cognitive function in patients with the elderly chronic schizophrenic, but the effect of social function is not clear.

Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.