Heat stroke (HS), also known as severe sunstroke, is one of the most serious heat-related disorders, characterized by rapid onset, rapid progression, aggressive condition, and high morbidity and mortality. The occurrence and development of HS are closely related to pathophysiological processes such as inflammation, oxidative stress, cell death, and coagulation failure. With the gradual discovery of the pathogenic mechanisms of HS, some drugs or therapeutic approaches targeting its molecular regulatory pathways have shown clinical promise. This review intends to provide an overview of research advances in HS types, pathogenic mechanisms, preclinical and clinically relevant therapeutic strategies, as well as to highlight the potential clinical applications of HS-related biomarkers and therapeutic targets with a view to informing the clinical management of HS.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Objective To screen the epithelial mesenchymal transformation(EMT)-related genes in lung adenocarcinoma,perform functional enrichment analysis and construct protein interaction network(PPI).Ac-cording to the competitive endogenous RNA(ceRNA)hypothesis and the effect of gene expression on the prognosis of patients,the ceRNA network was constructed.Methods The differentially expressed genes be-tween lung adenocarcinoma tissues and normal tissues were screened by gene expression map and tumor ge-nome map database,and the genes were imported into GenClip3 to obtain EMT-related genes.Metascape was used to perform gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis,and STRING database was used to construct PPI and obtain EMT key genes.The relationship between key genes and prog-nosis was analyzed by Kaplan-Meier analysis.Analysis tools such as miRTarbase,miRNet database,and EN-CORI were used to construct ceRNA networks.Results In this study,156 lung adenocarcinoma EMT-related genes and their key genes cadherin 1,interleukin-6,matrix metalloproteinase-9,platelet endothelial cell adhe-sion molecule,cyclin-dependent kinase inhibitor 2A,α1-Ⅰcollagen gene,secreted phosphoprotein 1,TIMP in-hibitor of matrix metalloproteinase-1,caveolin-1 and Zeste homologue enhance core 2(EZH2)-1 were identi-fied.The PPI of key genes was predicted,and the therapeutic drugs targeting these key genes including salvia miltiorrhiza,ginseng lu,ginseng leaf and ginseng flower were also predicted.The prognostic ceRNA regulatory network of EZH2/hsa-miR-101-3p/GSEC was constructed.Conclusion This study describes using bioinfor-matics methods system in the process of EMT gene interactions,according to the lung adenocarcinoma pa-tients clinical data to construct the prognosis of the EMT process related ceRNA network,for the treatment and prognosis of lung adenocarcinoma judgment provides a new way of thinking.

Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To verify the protective effect of terazosin on cognitive function of rats after whole-brain irradiation (WBI) and to investigate its mechanism.Methods:A total of 64 1-month-old male SD rats were randomly divided into the untreated control group, terazosin group, irradiation group and irradiation plus terazosin group (combination group). WBI was administered at a single dose of 20 Gy in the irradiation and combination groups. The open field test and the Morris water maze (MWM) test were used to evaluate the effect of terazosin on cognitive function after WBI.Starting from the three aspects of juvenile neuron apoptosis, neurogenesis disorderand microglia activation, the possible cellular mechanism wasassayed by double-label immunofluorescence staining for BrdU (bromodeoxyuridine) / NeuN, DCX(Doublecortin) / Caspase-3 and single-label immunofluorescence staining for Iba-1 (ionized calcium binding adaptor molecule-1).Results:Terazosin intervention improved the short-term memory retention of irradiated rats ( P=0.032). After terazosin treatment, the number of DCX + cells in the combination groupwas increased by approximately 35% compared with that in the irradiation group ( P=0.038). The number of BrdU +/NeuN + cells in the combination group was increased by approximately 15% than that in the irradiation group ( P>0.05). The number of Iba-1 + cells in the irradiation plus terazosin group was decreased by 49% compared with that in the irradiation group ( P=0.036). Conclusion:Terazosin may reduce the hippocampal juvenile neuron loss and inhibit neuroinflammation via microglia activation, which can alleviate WBI-induced cognitive dysfunction to a certain extent.

Objective:To investigate the efficacy and safety of radiotherapy for all metastases in patients with metachronous oligo-metastatic prostate cancer after radical treatment.Methods:From October 2011 to February 2021, 41 patients with prostate cancer with less than 5 metastases after radical treatment were retrospectively analyzed in a single center. The median age at radiotherapy was 68 (57-81) years. Forty patients (98%) received androgen deprivation therapy (ADT). There were 28 patients in the hormone sensitive (HSPC) group and 13 patients in the hormone resistant (CRPC) group. The median initial PSA was 24.4 (7.4-399.0) ng/ml. Tumor stage: T 2 stage 11 patients, T 3 stage 27 patients, T 4 stage 3 patients.30 patients were in N 0 stage and 11 patients in N 1 stage. Gleason score was 7 in 12 patients, 8 in 9 patients, 9 in 18 patients, and 10 in 2 patients.33 patients were treated with surgery, and 8 patients were treated with radiotherapy. The time span from diagnosis to metastasis was 3.1 (0.2-1.8) years. Conventional imaging examination (CT/ MRI/bone scan) before radiotherapy was used in 7 patients, and PSMA PET/CT examination was used in 34 patients.The median PSA before radiotherapy was 1.3(0.1-33.8) ng/ml. There were 62 metastases in 41 patients, including 1 lesion in 28 patients, 2 lesions in 9 patients, 3 lesions in 2 patients, and 5 lesions in 2 patients. Fifty-four patients had bone metastases and eight had retroperitoneal lymph node metastases. Twenty-two bone metastases were located in the pelvis, 18 in the vertebral body, 12 in the ribs, one in the femur and one in the sternum.The median metastatic volume was 5.8(0.2-81.7) cm 3.Daily image-guided rotational intensity modulated radiotherapy was used to cover all metastases.Dose segmentation modes include 37.5Gy/7.5Gy/5F, 60Gy/3Gy/20F, 65-70Gy/2.6-2.8Gy/25F.The median biological effective dose (BED 3) was 120 (67-147) Gy. The primary endpoint was biochemical progression-free survival (BPFS), the secondary endpoints were acute and late toxic side effects, local relapse-free survival (LPFS), and overall survival (OS). Results:The median follow-up time was 21 months (range 5-72 months). All patients completed radiotherapy, and 16 patients had grade 1 to 2 acute toxicity and side effects, and no grade 3 or above acute and late stage side effects. 1-year LPFS was 97.1%.The 1-year and 2-year BPFS were 77.5% and 59.2%, respectively. The median BPFS time was 29 months (range 13.9-44.2 months). Univariate analysis showed that the HSPC group ( P<0.001) and the group with total metastatic volume ≤ 5.8cm 3 ( P=0.010) had higher BPFS. The median BPFS time was 37 months in the retroperitoneal lymph node metastases subgroup and 17 months in the bone metastases subgroup ( P=0.141). In the HSPC group, the median BPFS was 30(22-38) months. After radiotherapy, PSA decreased in all 28 patients, and increased in 6 patients. The median BPFS was 12(4-18) months. In the CRPC group, the median BPFS was 4(0-8) months. PSA decreased in 10 patients (76.9%) after radiotherapy, and PSA decreased in 6 patients. The median BPFS was 5(3-28) months. Three patients’PSA did not decrease after radiotherapy, and they were treated with new endocrine therapy drugs, chemotherapy, immunotherapy and other systemic therapy. Conclusions:For patients with metachronous metastases after radical treatment, full coverage radiotherapy has good safety and high local control rate. HSPC patients and patients with low tumor load could be recommended to receive radiotherapy for all metastatic lesions preferentially, and patients with only retroperitoneal lymph node metastases may have better prognosis after radiotherapy than patients with bone metastases.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective:To investigate whether irradiated U251 glioma cells can induce bystander effects in unexposed neural stem cells (NSCs) thus affecting its proliferation, stemness and differentiation.Methods:The cells were divided into NSCs group, NSCs+ U251 group (co-cultured with U251) and NSCs+ IR U251 group (co-cultured with 10 Gy irradiated U251). Glioma cells and NSCs were co-cultured in a transwell insert set. Cell counting and neurosphere diameter measuring were carried out to evaluate the proliferation and neurosphere formation ability of NSCs. Immunofluorescence assay was performed to detect the expression of Nestin protein to evaluate the stemness maintenance of NSCs, and to measure the expression levels of Tuj1 and GFAP proteins, the number of neuronal dendrites, synaptic length, the number of glial protrusions, as well as the length of glial protrusions.Results:The number of NSCs cultured with irradiated U251 cells was obviously smaller than that of NSCs cultured with sham-irradiated U251 cells ( t=2.52, P<0.05). The neurosphere formation ability of NSCs and the percentage of Nestin positive NSCs after co-culture with irradiated U251 cells significantly reduced in comparison with those after co-culture with sham-irradiated U251 cells ( t=-3.50, P<0.05). The percentages and the extent of NSCs differentiating into neuronal cells and glial cells( t=6.09, P<0.05)decreased obviously after co-culture with irradiated U251 cells in comparison with those after co-culture with sham-irradiated U251 cells. Conclusions:Irradiated glioma cells can significantly inhibit the proliferation, stemness and differentiation of unexposed NSCs due to bystander effect.