BACKGROUND:Cellular pyroptosis is an important pathological mechanism of cerebral ischemia/reperfusion injury.Buyang Huanwu Tang is a classic formula for the clinical treatment of ischemic stroke in traditional Chinese medicine,and cellular pyroptosis may be an effective target of Buyang Huanwu Tang in the treatment of cerebral ischemia/reperfusion injury.OBJECTIVE:To observe the effect and mechanism of Buyang Huanwu Tang on pyroptosis in brain tissues of middle cerebral artery occlusion/reperfusion rats.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,model group,Astragalus membranaceus group and Buyang Huanwu Tang group.Except for the sham operation group,all groups were subjected to middle cerebral artery occlusion for ischemia for 2 hours and reperfusion for 72 hours.The rats in the Astragalus membranaceus group and Buyang Huanwu Tang group were continuously gavaged with the corresponding volume of drugs until ischemia and reperfusion for 72 hours after awakening from the modeling,once in the morning and once in the evening.Zea Longa score was used to observe the neurological deficits of rats.TTC staining was performed to observe cerebral infarct size in rats.Hematoxylin-eosin staining was used to observe the pathological changes of the brain tissue.Immunofluorescence was used to observe the co-expression of Tunel and Cleaved-Caspase-1 in the brain tissue and the expression of the junction protein ASC.Immunohistochemistry and western blot were used to detect the expression of pyroptosis-related proteins in rat brain tissues.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the neurological deficit score of rats was significantly higher in the model group(P<0.01),and compared with the model group,the neurological deficit score of rats was significantly lower in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).(2)Compared with the model group,the volume ratio of cerebral infarction was lower in the Astragalus membranaceus group and Buyang Huanwu Tang group(P<0.01).(3)In the model group,the nuclei of neuronal cells in the brain tissue were deeply stained or lysed,and arrangement of the cells was disorganized.Compared with the model group,the pathologic damage of the brain was less severe in the Buyang Huanwu Tang group and the Astragalus membranaceus group.(4)Compared with the sham operation group,the number of Tunel and Cleaved-Caspase-1 double-positive cells and immunofluorescence intensity of ASC in the brain tissue was significantly increased in the model group,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β was significantly elevated in the model group(P<0.01).Compared with the model group,the number of Cleaved-Caspase-1 and Tunel double-positive cells,immunofluorescence intensity of ASC,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β were all significantly decreased in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).The results indicate that Buyang Huanwu Tang and its monarch drug Astragalus membranaceus can effectively alleviate brain tissue injury in rats with middle cerebral artery occlusion and reperfusion,and its mechanism may be related to the inhibition of neuronal cell pyroptosis.

BACKGROUND:Cellular pyroptosis is an important pathological mechanism of cerebral ischemia/reperfusion injury.Buyang Huanwu Tang is a classic formula for the clinical treatment of ischemic stroke in traditional Chinese medicine,and cellular pyroptosis may be an effective target of Buyang Huanwu Tang in the treatment of cerebral ischemia/reperfusion injury.OBJECTIVE:To observe the effect and mechanism of Buyang Huanwu Tang on pyroptosis in brain tissues of middle cerebral artery occlusion/reperfusion rats.METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,model group,Astragalus membranaceus group and Buyang Huanwu Tang group.Except for the sham operation group,all groups were subjected to middle cerebral artery occlusion for ischemia for 2 hours and reperfusion for 72 hours.The rats in the Astragalus membranaceus group and Buyang Huanwu Tang group were continuously gavaged with the corresponding volume of drugs until ischemia and reperfusion for 72 hours after awakening from the modeling,once in the morning and once in the evening.Zea Longa score was used to observe the neurological deficits of rats.TTC staining was performed to observe cerebral infarct size in rats.Hematoxylin-eosin staining was used to observe the pathological changes of the brain tissue.Immunofluorescence was used to observe the co-expression of Tunel and Cleaved-Caspase-1 in the brain tissue and the expression of the junction protein ASC.Immunohistochemistry and western blot were used to detect the expression of pyroptosis-related proteins in rat brain tissues.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the neurological deficit score of rats was significantly higher in the model group(P<0.01),and compared with the model group,the neurological deficit score of rats was significantly lower in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).(2)Compared with the model group,the volume ratio of cerebral infarction was lower in the Astragalus membranaceus group and Buyang Huanwu Tang group(P<0.01).(3)In the model group,the nuclei of neuronal cells in the brain tissue were deeply stained or lysed,and arrangement of the cells was disorganized.Compared with the model group,the pathologic damage of the brain was less severe in the Buyang Huanwu Tang group and the Astragalus membranaceus group.(4)Compared with the sham operation group,the number of Tunel and Cleaved-Caspase-1 double-positive cells and immunofluorescence intensity of ASC in the brain tissue was significantly increased in the model group,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β was significantly elevated in the model group(P<0.01).Compared with the model group,the number of Cleaved-Caspase-1 and Tunel double-positive cells,immunofluorescence intensity of ASC,and the expression of Cleaved-Caspase-1,NLRP3,interleukin 18,and interleukin 1β were all significantly decreased in the Buyang Huanwu Tang group and the Astragalus membranaceus group(P<0.01).The results indicate that Buyang Huanwu Tang and its monarch drug Astragalus membranaceus can effectively alleviate brain tissue injury in rats with middle cerebral artery occlusion and reperfusion,and its mechanism may be related to the inhibition of neuronal cell pyroptosis.

Purpose To examine the contemporary state of pathological diagnosis for granulomatous lobular mastitis(GLM)in China.Methods Pathologists from across the nation were invited to engage in an online questionnaire survey,which ad-dressed pertinent topics such as the frequency of GLM diagnosis cases,the modalities of pathology reporting,and advancements in etiological research.The collected data were analyzed utili-zing the x2 test or Fisher's exact test.Results A survey of 702 pathologists included 26.9％(189/702)chief physicians,43.3％(304/702)deputy chief physician,26.1％(183/702)attending physicians,and 3.7％(26/702)residents.Partici-pants were from tertiary general hospitals(77.6％,545/702),traditional Chinese medicine hospitals(7.7％,54/702),ma-ternal and child specialty hospitals(6.1％,43/702),and on-cology specialty hospitals(4.0％,28/702).In 2023,there were over 45,000 mastitis diagnoses.A significantly higher per-centage of chief physicians(60.8％,115/189)and deputy chief physicians(52.6％,160/304)could diagnose specific mastitis types compared to attending and resident physicians(x2=23.537,P＜0.001),with"GLM"being the most common diagnosis(55.1％,81/147).In diagnostic work,78.06％(548/702)of pathologists consider patient clinical information,19.2％(135/702)screen specimens for pathogens using special staining,only 6.0％(42/702)of pathologists indicated that their hospitals routinely perform tissue culture for pathogens,with corynebacterium being the most common.Additionally,11.4％(80/702)reported that clinicians regularly test serum sex hormones,most frequently for elevated prolactin,while 7.1％(50/702)check autoimmune status,frequently detecting antibodies without clinical symptoms.Chief physicians had a significantly better understanding of the etiology of GLM com-pared to other physicians(x2=11.969,P=0.003;P=0.007).A majority of pathologists indicated a lack of guidelines for GLM pathology diagnosis(49.4％,347/702)and report standards(76.4％,536/702).Nearly all(97.4％)agreed on the need to establish a consensus for GLM diagnosis.Conclu-sion GLM pathological diagnosis is currently inconsistent and lacks standardization,highlighting the urgent need for a guiding consensus for pathologists.

Background With urbanization and residential space expansion, ecological environment and human health issues have become hot social topics. Forest health, as a way of seeking health in nature, has begun to receive public attention in the context of the gradually increasing sub-healthy population and various psychological and physical diseases at a young age. Objective To systematically evaluate the effects of forest therapy on selected physical and mental health indicators. Methods Relevant research literature was retrieved from domestic and international databases (China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Service System, Web of Science, ScienceDirect, PubMed, Embase, and Cochrane Library), with a time range from database establishment to January 31, 2023. Relevant data were extracted for meta-analysis to explore the relationship between forest therapy and selected psychological and physiological indicators. Results A total of 85 articles were included, and the meta-analysis results showed that better scores of Profile of Mood States, Positive and Negative Affect Scale, Beck Depression Inventory, and State Trait Anxiety Scale were found in the forest group than those in the urban group (P<0.05); the levels of systolic blood pressure, diastolic blood pressure, heart rate, sympathetic nerve indicator [ln (LF/HF)], salivary cortisol, and serum inflammatory factors were lower in the forest group than in the urban group, while parasympathetic nerve indicator [ln (HF)] level was higher in the forest group than in the urban group (P<0.05). The results of subgroup analysis showed that the changes in heart rate (SMD=−1.62, 95%CI: −2.41, −0.82), ln (HF) (SMD=1.29, 95%CI: 0.73, 1.85), ln (LF/HF) (SMD=−1.49, 95%CI: −2.13, −0.86), and salivary cortisol (SMD=−0.53, 95%CI: −0.81, −0.25) were more significant when the duration of forest therapy was ≤ 0.5 h, the recovery effect on emotional state was better in the >0.5~3 h group (such as tension SMD=−2.40, 95%CI: −3.21, 1.59), and the reduction effects on systolic blood pressure (SMD=−0.53, 95%CI: −1.03, −0.03) and diastolic blood pressure (SMD=−0.42, 95%CI: −0.88, 0.04) were better in the >3 h group. Seated meditation showed better recovery effects on multiple indicators of Profile of Mood States (such as fatigue SMD=−2.26, 95%CI: −3.07, −1.45), while walking showed better recovery effects on physiological indicators such as blood pressure (systolic blood pressure SMD=−0.57, 95%CI: −1.07, −0.06; diastolic blood pressure SMD=−0.72, 95%CI: −1.36, −0.07) and heart rate (SMD=−1.51, 95%CI: −2.38, -0.64). Except for blood pressure, the health benefits of forest therapy in the younger age group were generally better than those in the middle-aged and elderly group. Conclusion Relaxed and comfortable psychological feeling is reported when practicing forest therapy; it can lower blood pressure and heart rate, regulate the autonomic nervous system; it can also reduce the release of stress hormones and lower serum levels of inflammatory factors, exerting an auxiliary recovery effect on cardiovascular and immune system disorders. At the same time, the therapy duration, form, and age of the subjects have a certain impact on the effects of forest therapy practice.

Purpose To examine the contemporary state of pathological diagnosis for granulomatous lobular mastitis(GLM)in China.Methods Pathologists from across the nation were invited to engage in an online questionnaire survey,which ad-dressed pertinent topics such as the frequency of GLM diagnosis cases,the modalities of pathology reporting,and advancements in etiological research.The collected data were analyzed utili-zing the x2 test or Fisher's exact test.Results A survey of 702 pathologists included 26.9％(189/702)chief physicians,43.3％(304/702)deputy chief physician,26.1％(183/702)attending physicians,and 3.7％(26/702)residents.Partici-pants were from tertiary general hospitals(77.6％,545/702),traditional Chinese medicine hospitals(7.7％,54/702),ma-ternal and child specialty hospitals(6.1％,43/702),and on-cology specialty hospitals(4.0％,28/702).In 2023,there were over 45,000 mastitis diagnoses.A significantly higher per-centage of chief physicians(60.8％,115/189)and deputy chief physicians(52.6％,160/304)could diagnose specific mastitis types compared to attending and resident physicians(x2=23.537,P＜0.001),with"GLM"being the most common diagnosis(55.1％,81/147).In diagnostic work,78.06％(548/702)of pathologists consider patient clinical information,19.2％(135/702)screen specimens for pathogens using special staining,only 6.0％(42/702)of pathologists indicated that their hospitals routinely perform tissue culture for pathogens,with corynebacterium being the most common.Additionally,11.4％(80/702)reported that clinicians regularly test serum sex hormones,most frequently for elevated prolactin,while 7.1％(50/702)check autoimmune status,frequently detecting antibodies without clinical symptoms.Chief physicians had a significantly better understanding of the etiology of GLM com-pared to other physicians(x2=11.969,P=0.003;P=0.007).A majority of pathologists indicated a lack of guidelines for GLM pathology diagnosis(49.4％,347/702)and report standards(76.4％,536/702).Nearly all(97.4％)agreed on the need to establish a consensus for GLM diagnosis.Conclu-sion GLM pathological diagnosis is currently inconsistent and lacks standardization,highlighting the urgent need for a guiding consensus for pathologists.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.