ObjectiveDonkey hide is the sole legally designated raw material for the preparation of the traditional Chinese medicine Ejiao. The quality stability of donkey hide during preservation directly determines the efficacy and safety of Ejiao. This study focuses on the dynamic succession of microbial communities during the preservation of donkey hides from different origins, aiming to clarify the correlation between microbial biodiversity difference and the degradation profiles of hide collagen and critical biochemical components, thereby providing a theoretical foundation for developing targeted preservation strategies based on microbial regulation. MethodsDonkey hides originating from four different regions were subjected to an accelerated microbial aging assay to simulate the spoilage process. The microbial community succession was analyzed using high-throughput sequencing. Microstructure changes and pore structure characteristics were assessed by scanning electron microscopy and mercury intrusion porosimetry, respectively. Additionally, the content of major components, including lipids, proteins, and sugars were determined by biochemical methods. ResultsAfter 96 h of aging, the collagen fiber structure in Africa donkey hides (ADH) exhibited significant degradation and collapse, followed by Xinjiang donkey hides (XDH). Instead, the microstructure of Dong’e black donkey hides (DDH) and Peru donkey hides (PDH) remained relatively intact. The porosities of DDH, XDH, PDH, and ADH increased from 27.9%, 15.7%, 30.3%, and 46.2% to 36.5%, 52.6%, 42.8%, and 57.7%, respectively, during the aging process, which suggested that the originally compact fiber structure was disrupted by microbial aging. Fourier transform infrared spectrometer analysis revealed the amide bands in XDH exhibited relatively weak intensity, and no collagen amide I band was observed in ADH. Meanwhile, the lipid and protein contents decreased in all four types of donkey hides, indicating that these components served as the primary nutrient sources for the growth of microorganism. Notably, the most severe collagen degradation was observed in XDH and ADH. A substantial increase was detected in the total soluble sugar in PDH aging solution and hydroxyproline in the ADH aging solution, respectively. These results indicated that donkey hides exhibit distinct patterns of structural degradation and nutrient utilization. Furthermore, the viable cells number of donkey hides increased sharply after 48 h of aging. Metagenomic analysis revealed that the relative abundance of Euryarchaeota in ADH, PDH and XDH declining from initial 93.19%, 97.73% and 30.08% to 0.79%, 1.43% and 0.02% after 96 h, respectively. Conversely, a significantly increase was observed in the abundance of Bacillota, with a marked increase in ADH, peaking at 92.75%. Additionally, the abundance of Pseudomonadota in PDH increased from 0.10% to 87.84%, suggesting that Bacillota and Pseudomonadota may be key factors exacerbating donkey hide spoilage. Unlike the other three types of donkey hides, the dominant bacterial phylum in DDH shifted from Pseudomonadota to Bacteroidota, characterized by a substantial abundance increase of Bacteroidota from 0.13% to 44.22%. ConclusionRegional variation in origin significantly influence the microbial aging of donkey hides, leading to distinct patterns of structural deterioration and differential nutrient utilization. Therefore, implementing origin-specific preservation strategies, through the precisely controlling environmental factors to suppress harmful phyla such as Bacillota and Pseudomonadota, is crucial for enhancing the storage quality of donkey hides.

Objective: To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures. Methods: Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC). Results: A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively. Conclusions The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.

Objective:To present a set of clinically representative quality assurance (QA) test cases for stereotactic radiosurgery (SRT) plans of multiple intracranial metastases, in order to assess the plan quality and machine execution capabilities.Methods:Based on the clinical characteristics of multiple brain metastases, four groups of test cases with three target volumes (TVs), six TVs, nine TVs, and TVs near organs at risk (OARs) were designed. For these cases, SRT plans were developed, and plan quality was assessed using metrics including the Radiation Therapy Oncology Group conformality index (RTOG CI), gradient index (GI), homogeneity index (HI), and the volume of normal brain tissue receiving a dose of 24 Gy ( V24 Gy), which was defined as the volume enclosed by the 24 Gy isodose line around the Brain-PTV ( V24 Gy of Brain-PTV). Verification plans were generated for each test case, including the verification of point doses, planar doses (PD), and SRS MapCHECK (SMC) semiconductor matrix planar doses. Compared with the calculated result of the treatment planning system (TPS), the criteria for the γ analysis of planar doses were set at 1 mm/2% and 2 mm/2%. Results:For the four groups of test cases, the mean CI, GI, HI, and V24 Gy of Brain-PTV were 1.04±0.03, 3.79±0.40, 0.73±0.01 and (7.46±3.80) cm 3, respectively. The mean deviations of the point doses were 0.88%±0.98%, 1.47%±0.79%, 1.52%± 0.76%, and 1.17% ± 0.38%, respectively. The mean γ passing rates of the single fields for PDs were greater than 98% at 2 mm/2% and exceeding 96% at 1 mm/2%, and the mean γ pass rates of the SMC semiconductor matrix for PDs were 97.75% ± 2.31% and 99.33% ± 0.62%, at 1 mm/2% and 2 mm/2% respectively. Conclusions:The proposed QA test cases for SRT of multiple intracranial metastases allow for the effective assessments of the plan quality and machine execution capabilities and, thus, can assist various centers in clinical applications.

Objective:To present a set of clinically representative quality assurance (QA) test cases for stereotactic radiosurgery (SRT) plans of multiple intracranial metastases, in order to assess the plan quality and machine execution capabilities.Methods:Based on the clinical characteristics of multiple brain metastases, four groups of test cases with three target volumes (TVs), six TVs, nine TVs, and TVs near organs at risk (OARs) were designed. For these cases, SRT plans were developed, and plan quality was assessed using metrics including the Radiation Therapy Oncology Group conformality index (RTOG CI), gradient index (GI), homogeneity index (HI), and the volume of normal brain tissue receiving a dose of 24 Gy ( V24 Gy), which was defined as the volume enclosed by the 24 Gy isodose line around the Brain-PTV ( V24 Gy of Brain-PTV). Verification plans were generated for each test case, including the verification of point doses, planar doses (PD), and SRS MapCHECK (SMC) semiconductor matrix planar doses. Compared with the calculated result of the treatment planning system (TPS), the criteria for the γ analysis of planar doses were set at 1 mm/2% and 2 mm/2%. Results:For the four groups of test cases, the mean CI, GI, HI, and V24 Gy of Brain-PTV were 1.04±0.03, 3.79±0.40, 0.73±0.01 and (7.46±3.80) cm 3, respectively. The mean deviations of the point doses were 0.88%±0.98%, 1.47%±0.79%, 1.52%± 0.76%, and 1.17% ± 0.38%, respectively. The mean γ passing rates of the single fields for PDs were greater than 98% at 2 mm/2% and exceeding 96% at 1 mm/2%, and the mean γ pass rates of the SMC semiconductor matrix for PDs were 97.75% ± 2.31% and 99.33% ± 0.62%, at 1 mm/2% and 2 mm/2% respectively. Conclusions:The proposed QA test cases for SRT of multiple intracranial metastases allow for the effective assessments of the plan quality and machine execution capabilities and, thus, can assist various centers in clinical applications.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

Epilepsy is a chronic disease characterized by recurrent,sudden,and excessive synchronous discharge of neurons in the brain,leading to transient brain dysfunction,and inflammatory responses in specific regions within the central nervous system are common features of epilepsy.In recent years,there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy,which activates the unfolded protein response,then regulate and control nuclear factor kappa-B(NF-κB),efficiently induces glial cell activation through the release of pro-inflammatory signals,in turn affects epileptogenesis and seizures by triggering neuroinflammation.This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology,aiming to provide insights for a deeper understanding of epilepsy.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F