OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

Objective:To observe the improving effects of Tuina(Chinese therapeutic massage)plus exercise therapy on joint alignment and walking function in children with genu varum(GV).Methods:Sixty-six children with GV were divided into an exercise therapy group and a Tuina plus exercise therapy group using the random number table method,with 33 cases in each group.Both groups received identical exercise therapy,while the Tuina plus exercise therapy group was additionally offered Tuina manipulation treatment.The intervention course lasted 12 weeks in both groups.Before and after the intervention,the three-dimensional gait analysis was adopted to assess the spatiotemporal parameters,kinematics,and kinetic characteristics of lower-limb joints in children with GV.Results:The GV angle was reduced after intervention in the Tuina plus exercise therapy group(P<0.05),but there was no significant change in the exercise therapy group(P>0.05).After treatment,the Tuina plus exercise therapy group demonstrated a notable decrease in the step length,walking speed,peak forefoot adduction angle,and peak ankle inversion moment(P<0.05),suggesting the correction of the ankle joint's compensatory pathological changes.In the exercise therapy group,the foot progression angle(FPA)and gait deviation index(GDI)increased markedly after the intervention(P<0.05),indicating improved overall kinematic function.Conclusion:The combined use of Tuina manipulations and exercise therapy can produce significant effects in correcting the knee joint's torsion,both coronally(GV angle)and horizontally(ankle inversion moment,FPA,and forefoot adduction angle),while exercise therapy alone can markedly improve the overall kinematic parameters(FPA and GDI).

Objective:To establish a rapid quantitative model for the determination of moisture,extractives,and content in Pollen Typhae.Methods:Near-infrared spectra of 91 batches of Pollen Typhae samples were collected.Spectral preprocessing was performed using S-G,MSC,SNV,and CWT methods.Variable selection was conducted using CARS,SPA,and VIP methods,and compared with full-spectrum modeling.Partial least squares(PLS)mod-els were established for the quantitative determination of moisture,total ash,extractives,and content.The model performance was evaluated by calculating the coefficient of determination for the calibration set and validation set(R2 c,R2v),root mean square error of calibration and validation(RMSEc,RMSEv),and residual prediction devia-tion(RPD).Results:The PLS models for moisture,extractives,and content in Pollen Typhae showed R2c and R2v values greater than 0.9,RMSEc and RMSEv values approaching 0,and RPD values greater than 3.Conclusion:In this study,near-infrared spectroscopy was used to construct quantitative prediction models for moisture,extractives,typhaneoside,and isorhamnetin-3-O-neohesperidoside content in Pollen Typhae.This method enables rapid detection of the main quality control indicators of Pollen Typhae,providing strong technical support for its quality supervision.

Objective:To establish a rapid quantitative model for the determination of moisture,extractives,and content in Pollen Typhae.Methods:Near-infrared spectra of 91 batches of Pollen Typhae samples were collected.Spectral preprocessing was performed using S-G,MSC,SNV,and CWT methods.Variable selection was conducted using CARS,SPA,and VIP methods,and compared with full-spectrum modeling.Partial least squares(PLS)mod-els were established for the quantitative determination of moisture,total ash,extractives,and content.The model performance was evaluated by calculating the coefficient of determination for the calibration set and validation set(R2 c,R2v),root mean square error of calibration and validation(RMSEc,RMSEv),and residual prediction devia-tion(RPD).Results:The PLS models for moisture,extractives,and content in Pollen Typhae showed R2c and R2v values greater than 0.9,RMSEc and RMSEv values approaching 0,and RPD values greater than 3.Conclusion:In this study,near-infrared spectroscopy was used to construct quantitative prediction models for moisture,extractives,typhaneoside,and isorhamnetin-3-O-neohesperidoside content in Pollen Typhae.This method enables rapid detection of the main quality control indicators of Pollen Typhae,providing strong technical support for its quality supervision.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

This case report describes the diagnostic and therapeutic management of a 67-year-old fe-male with a 40-year history of Sj?gren disease(SjD)who was hospitalized for evaluation of recurrent fever lasting over one month.The patient's initial diagnosis of SjD was established four decades earlier based on clinical manifestations,serological findings,and evidence of glandular damage.Her clinical presenta-tion included recurrent parotid gland enlargement accompanied by sicca symptoms,notably persistent xerostomia and xerophthalmia,followed by progressive dental caries.Serological studies demonstrated positivity for antinuclear antibodies,anti-SSA/Ro,and anti-α-fodrin antibodies.Objective assessments confirmed significant ocular involvement(Schirmer's test≤5 mm/5 min)and pulmonary interstitial changes on chest CT,consistent with the 2016 American College of Rheumatology and European League Against Rheumatism(ACR/EULAR)classification criteria for SjD.The patient's condition remained sta-ble under low-dose corticosteroids and disease-modifying anti-rheumatic drugs(DMARDs)until the re-cent onset of prolonged fever,necessitating evaluation for fever of unknown origin.Differential diagnoses considered disease flare,infection,and malignancy.The European Sj?gren's Syndrome Disease Activity Index(ESSDAI)score was 5 points,indicating moderate systemic disease activity.Initial laboratory in-vestigations revealed no evidence of infection,and empirical anti-infective therapy proved ineffective.No-tably,despite the absence of lymphadenopathy,laboratory findings including borderline positive IgM λ M-protein,elevated lactate dehydrogenase,hyperferritinemia,and increased β2-microglobulin levels raised suspicion for lymphoproliferative disorders,given the established association between SjD and lymphoma.Bone marrow aspiration showed no significant abnormalities,but PET/CT imaging detected hypermetabolic lesions in the left breast and right distal femur,suggesting potential malignancy.Subse-quent histopathological examination of the breast lesion confirmed non-Hodgkin's lymphoma(NHL),specifically diffuse large B-cell lymphoma(DLBCL)of the germinal center B-cell(GCB)subtype.Treatment with R-CHOP chemotherapy(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)induced complete metabolic remission after three cycles.However,she subsequently developed treatment-related complications,including myelosuppression and pulmonary infection.This case underscores the importance of maintaining a high index of suspicion for atypical site involvement in SjD patients,particularly when lymphoma risk factors are present.Comprehensive differential diagnosis should include lymphoma and other malignancies,and the diagnostic value of PET/CT and histopatholog-ical examination in disease evaluation is emphasized.SjD complicated by breast lymphoma is exceptional-ly rare,and its pathogenesis may involve lymphocytic infiltration,abnormal activation of lymphocytes,formation of ectopic germinal centers in the breast,and eventual malignant transformation.These mecha-nisms require further investigation through clinical and basic research studies.

This case report describes the diagnostic and therapeutic management of a 67-year-old fe-male with a 40-year history of Sj?gren disease(SjD)who was hospitalized for evaluation of recurrent fever lasting over one month.The patient's initial diagnosis of SjD was established four decades earlier based on clinical manifestations,serological findings,and evidence of glandular damage.Her clinical presenta-tion included recurrent parotid gland enlargement accompanied by sicca symptoms,notably persistent xerostomia and xerophthalmia,followed by progressive dental caries.Serological studies demonstrated positivity for antinuclear antibodies,anti-SSA/Ro,and anti-α-fodrin antibodies.Objective assessments confirmed significant ocular involvement(Schirmer's test≤5 mm/5 min)and pulmonary interstitial changes on chest CT,consistent with the 2016 American College of Rheumatology and European League Against Rheumatism(ACR/EULAR)classification criteria for SjD.The patient's condition remained sta-ble under low-dose corticosteroids and disease-modifying anti-rheumatic drugs(DMARDs)until the re-cent onset of prolonged fever,necessitating evaluation for fever of unknown origin.Differential diagnoses considered disease flare,infection,and malignancy.The European Sj?gren's Syndrome Disease Activity Index(ESSDAI)score was 5 points,indicating moderate systemic disease activity.Initial laboratory in-vestigations revealed no evidence of infection,and empirical anti-infective therapy proved ineffective.No-tably,despite the absence of lymphadenopathy,laboratory findings including borderline positive IgM λ M-protein,elevated lactate dehydrogenase,hyperferritinemia,and increased β2-microglobulin levels raised suspicion for lymphoproliferative disorders,given the established association between SjD and lymphoma.Bone marrow aspiration showed no significant abnormalities,but PET/CT imaging detected hypermetabolic lesions in the left breast and right distal femur,suggesting potential malignancy.Subse-quent histopathological examination of the breast lesion confirmed non-Hodgkin's lymphoma(NHL),specifically diffuse large B-cell lymphoma(DLBCL)of the germinal center B-cell(GCB)subtype.Treatment with R-CHOP chemotherapy(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)induced complete metabolic remission after three cycles.However,she subsequently developed treatment-related complications,including myelosuppression and pulmonary infection.This case underscores the importance of maintaining a high index of suspicion for atypical site involvement in SjD patients,particularly when lymphoma risk factors are present.Comprehensive differential diagnosis should include lymphoma and other malignancies,and the diagnostic value of PET/CT and histopatholog-ical examination in disease evaluation is emphasized.SjD complicated by breast lymphoma is exceptional-ly rare,and its pathogenesis may involve lymphocytic infiltration,abnormal activation of lymphocytes,formation of ectopic germinal centers in the breast,and eventual malignant transformation.These mecha-nisms require further investigation through clinical and basic research studies.

Objective:To observe the improving effects of Tuina(Chinese therapeutic massage)plus exercise therapy on joint alignment and walking function in children with genu varum(GV).Methods:Sixty-six children with GV were divided into an exercise therapy group and a Tuina plus exercise therapy group using the random number table method,with 33 cases in each group.Both groups received identical exercise therapy,while the Tuina plus exercise therapy group was additionally offered Tuina manipulation treatment.The intervention course lasted 12 weeks in both groups.Before and after the intervention,the three-dimensional gait analysis was adopted to assess the spatiotemporal parameters,kinematics,and kinetic characteristics of lower-limb joints in children with GV.Results:The GV angle was reduced after intervention in the Tuina plus exercise therapy group(P<0.05),but there was no significant change in the exercise therapy group(P>0.05).After treatment,the Tuina plus exercise therapy group demonstrated a notable decrease in the step length,walking speed,peak forefoot adduction angle,and peak ankle inversion moment(P<0.05),suggesting the correction of the ankle joint's compensatory pathological changes.In the exercise therapy group,the foot progression angle(FPA)and gait deviation index(GDI)increased markedly after the intervention(P<0.05),indicating improved overall kinematic function.Conclusion:The combined use of Tuina manipulations and exercise therapy can produce significant effects in correcting the knee joint's torsion,both coronally(GV angle)and horizontally(ankle inversion moment,FPA,and forefoot adduction angle),while exercise therapy alone can markedly improve the overall kinematic parameters(FPA and GDI).

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Objective:To analyze the association between sleep status and ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.Methods:It was a cross sentional study. Hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring from May 2021 to April 2023 in Shanghai Xinzhuang Town were enrolled. The demographic information and sleep status of patients were obtained from the questionnaire. A TM-2430 blood pressure monitor was used to measure 24-hour ambulatory blood pressure, and the relevant indicators, including blood pressure level and blood pressure coefficient of variation were documented. The association between sleep status and blood pressure indicators was analyzed with multivariate linear regression model.Results:A total 1 135 patients aged (65.07±12.61) years were enrolled, and 473 (41.67%) of whom were males. The sleep time was<7 hours in 76 cases, 7- 8 hours in 219 cases and >8 hours in 840 cases; the bedtime was earlier than 22∶00 in 415 cases, between 22∶00 and 23∶00 in 474 cases and later than 23∶00 in 246 cases; the wake-up time was before 6∶00 in 230 cases, between 6∶00 and 7∶00 in 521 cases and after 7∶00 in 384 cases. Multivariate linear regression analysis showed that after controlling for gender and age, the sleep time was negatively associated with diurnal, noctumal and 24-hour diastolic blood pressure levels (all P<0.05), and positively associated with diurnal and noctumal systolic blood pressure coefficient of variation, noctumal diastolic blood pressure coefficient of variation, and 24-hour systolic blood pressure coefficient of variation (all P<0.05).The bedtime was positively associated with diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), diastolic blood pressure (all P<0.05); and negatively associated with diurnal systolic blood pressure coefficient of variation, diurnal diastolic blood pressure coefficient of variation, noctumal systolic blood pressure coefficient of variation, 24-hour systolic blood pressure coefficient of variation, and 24-hour diastolic blood pressure coefficient of variation (all P<0.05). The wake-up time was positively associated with diurnal systolic blood pressure, diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), and positively associated with diurmal systolic blood pressure and diastolic blood pressure (both P<0.05). Conclusion:Sleep status is closely associated with ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.