1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Advances in the Application of Forensic Microbiome Analysis in Tissue Source Inference
Hewen YAO ; Chaoran SUN ; Shuangshuang WANG ; Yuxiang ZHOU ; Zhirui ZHANG ; Feng SONG ; Haibo LUO
Journal of Sichuan University (Medical Sciences) 2025;56(5):1419-1426
Forensic microbiology,a pivotal discipline within forensic science,focuses on microorganisms as the primary subject of study and applies life science technologies to analyze microbial evidence in criminal and civil investigations.Tissue source inference plays a crucial role in forensic investigations,facilitating case assessment and crime scene reconstruction.The application of microbiome analysis in tissue source inference benefits from the tissue specificity and spatiotemporal stability of human microbial communities.This article provides a systematic review of recent advances in tissue source inference based on microbiome analysis,covering technological development,research trends,and practical applications.Finally,the challenges confronted in practice in forensic microbiology and the future prospects for its development are summarized.
3.Molecular epidemiological investigation of Babesia infection in small mammals in the Jinsha River Basin,Yunnan Province
Fan WANG ; Yun ZHANG ; Zongti SHAO ; Yuqiong LI ; Ennian PU ; Zhihai HE ; Mingguo YAO ; Shuangshuang BIE ; Jiafu JIANG ; Chunhong DU
Chinese Journal of Zoonoses 2025;41(7):767-774
This study was aimed at understanding the Babesia species makeup and distribution in small mammals in Jinsha River Basin of Yunnan Province,and the Babesia carriage status in small mammals in this area,to provide a scientific basis for the preven-tion and control of Babesia disease.A total of 1 493 small mammals belonging to 5 orders,10 families,25 genera,and 54 species were captured from 10 counties(cities)in the Jinsha River Basin of Yunnan Province in various agricultural and forest environments.DNA was extracted from liver and tick tissues,and 150 bp fragments of Babesia 18S rRNA were detected through molecular biological methods.The positive samples showed amplification of a 1 600 bp target fragment of 18S rRNA.Species characteristics were assessed through sequence comparison and phylogenetic analysis.A total of 14 small mammals infected with Babesia were detected in six coun-ties(cities)of Jinsha River Basin,Yunnan Province,with a positivity rate of 0.93%(14/1 493).The Otsu and Kobe types of Babesia voles were analyzed,and their sequences were compared with the sequences from human Babesia cases with high similarity and close evolutionary relationships.The positivity rates were 2.34%(3/128)in Qiaojia County,2.06%(2/97)in Yongshan County,1.88%(4/213)in Yuanmou County,1.03%(3/291)in Deqin County,0.95%(1/105)in Shangri-La City,and 0.78%(1/128)in Shuifu County.The positive small mammals belonged to one order,two families,six genera,and the following eight species:P.leucurus 5.56%(1/18),R.brunneusculus 3.36%(4/119),M.minutus 3.33%(1/30),E.custos 2.94%(1/34),N.confucianus 2.65%(3/113),N.fulvescens 2.35%(2/85),A.latronum 1.16%(1/86),and A.draco 0.98%(1/102).The detection of Babesia in M.minutus was re-poorted first time.Small animals infected with Babesia were detected in all three habitats and altitudes,and higher infection rates were observed in forest regions between 1 500 and 2 500 meters and high-altitude residential areas.Babesia infection was found in many small mammals in several counties(cities)along Jinsha River in Yunnan Province,and the epidemic status of Babesia in these areas warrants attention.
4.Molecular epidemiological investigation of Babesia infection in small mammals in the Jinsha River Basin,Yunnan Province
Fan WANG ; Yun ZHANG ; Zongti SHAO ; Yuqiong LI ; Ennian PU ; Zhihai HE ; Mingguo YAO ; Shuangshuang BIE ; Jiafu JIANG ; Chunhong DU
Chinese Journal of Zoonoses 2025;41(7):767-774
This study was aimed at understanding the Babesia species makeup and distribution in small mammals in Jinsha River Basin of Yunnan Province,and the Babesia carriage status in small mammals in this area,to provide a scientific basis for the preven-tion and control of Babesia disease.A total of 1 493 small mammals belonging to 5 orders,10 families,25 genera,and 54 species were captured from 10 counties(cities)in the Jinsha River Basin of Yunnan Province in various agricultural and forest environments.DNA was extracted from liver and tick tissues,and 150 bp fragments of Babesia 18S rRNA were detected through molecular biological methods.The positive samples showed amplification of a 1 600 bp target fragment of 18S rRNA.Species characteristics were assessed through sequence comparison and phylogenetic analysis.A total of 14 small mammals infected with Babesia were detected in six coun-ties(cities)of Jinsha River Basin,Yunnan Province,with a positivity rate of 0.93%(14/1 493).The Otsu and Kobe types of Babesia voles were analyzed,and their sequences were compared with the sequences from human Babesia cases with high similarity and close evolutionary relationships.The positivity rates were 2.34%(3/128)in Qiaojia County,2.06%(2/97)in Yongshan County,1.88%(4/213)in Yuanmou County,1.03%(3/291)in Deqin County,0.95%(1/105)in Shangri-La City,and 0.78%(1/128)in Shuifu County.The positive small mammals belonged to one order,two families,six genera,and the following eight species:P.leucurus 5.56%(1/18),R.brunneusculus 3.36%(4/119),M.minutus 3.33%(1/30),E.custos 2.94%(1/34),N.confucianus 2.65%(3/113),N.fulvescens 2.35%(2/85),A.latronum 1.16%(1/86),and A.draco 0.98%(1/102).The detection of Babesia in M.minutus was re-poorted first time.Small animals infected with Babesia were detected in all three habitats and altitudes,and higher infection rates were observed in forest regions between 1 500 and 2 500 meters and high-altitude residential areas.Babesia infection was found in many small mammals in several counties(cities)along Jinsha River in Yunnan Province,and the epidemic status of Babesia in these areas warrants attention.
5.Factors associated with nursery care institution attendance for children aged 0 - 3 years old and the basic characteristics of nursery care institutions that children were enrolled in
Wenhong DONG ; Xinmeng YAO ; Xin XU ; Lina LYU ; Shasha WANG ; Shuangshuang ZHENG ; Lei WANG ; Bingquan ZHU ; Jie SHAO
Chinese Journal of Child Health Care 2024;32(2):122-126
【Objective】 To understand factors associated with children′s attendance at nursery care institutions (NCIs) and the basic characteristics of the NCIs children were enrolled in, so as to provide scientific evidence for policymakers. 【Methods】 During November 2020 and January 2021, parents who visited the Department of Child Health Care in six selected maternal and children′s hospitals, as well as nearby NCIs in Zhejiang were invited to finish an online questionnaire. Information such as children′s sociodemographic characteristics, parents′ knowledge, attitude and practice regarding nursery and feeding, etc. were collected. A total of 1 756 questionnaires were collected. 【Results】 Compared to children who were not in NCIs, children enrolled in NCIs were older (94.4% of children ≥24 months vs. 30.1%, χ2=835.27), more likely to be from the local area (87.2% vs. 81.4%,χ2=12.25), more likely to have parents with a college degree (mother: 83.6% vs. 74.2%, χ2=35.29; father: 79.9% vs. 70.0%, χ2=27.01), had a higher prevalence of family annual income >200 000 CNY (49.5% vs. 28.2%, χ2=110.49), and were less likely to have their grandparents available to take care of them (16.7% vs. 26.8%, χ2=31.4) The difference all have great significant.(P<0.05). In a multivariate Logistic regression model, the older the child, the more likely they were to attend an NCI (for children aged 6 - 23 months, OR=6.70; for children aged 24 - 35 months, OR=134.03; and for children aged 36 - 42 months, OR=699.33; P<0.05). Family annual income was positively associated with children′s attendance at NCIs (for those earning 100 000 - 200 000 CNY/year, OR=1.63; for those earning 200 000 - 500 000 CNY/year, OR=2.96; and for those earning >500 000 CNY/year, OR=4.62, P<0.05). Conversely, the higher the level of grandparent involvement in daily care, the lower the attendance at NCIs (for children cared for by both parents and grandparents, OR=0.57; for those primarily cared for by grandparents, OR=0.26, P<0.05). For children who used to stay at NCIs, 82.8% stayed at institutions that only recruited children aged 0 - 3 years, 97.4% spent their whole day in NCIs, and 71.4% spent less than 3 000 CNY per month for NCI services. Additionally, over 95% of parents were satisfied with the food and care services in NCIs, as well as their children′s physical development in NCIs. However, 32.1% of NCIs were reported by parents as having no room for breastfeeding. 【Conclusions】 Children′s age, grandparent involvement in routine care, and family annual income are the main factors associated with children′s attendance at NCIs. There is a greater need for more affordable and community-based NCIs, particularly for children under 2 years old. Additionally, more attention should be paid to the quality surveillance, assessment and management of NCIs.
6.Efficacy comparison of 0.01% atropine eye drops combined with defocus incorporated multiple segment spectacle lenses or highly aspherical lenslets in delaying the progression of myopia in adolescents
Xiang LI ; Xiaoli MAO ; Shuangshuang YAO
International Eye Science 2024;24(10):1640-1644
AIM: To compare the effects of defocus incorporated multiple segments(DIMS)lens with highly aspherical lenslets(HAL)on delaying the progression of myopia in adolescents.METHODS: Clinical randomized controlled study. Totally 301 students aged 7-12 who underwent optometry in our hospital from January 2021 to June 2023 were randomly divided into two groups. The first group consisted of 154 patients who were fitted with DIMS lenses(DIMS group). In the second group, 147 cases were fitted with HAL(HAL group). Both groups used 0.01% atropine eye drops to control myopia and all students wore glasses for more than 12 h every day. The spherical equivalent(SE)and axial length(AL)after rapid mydriasis were recorded. The data of the right eyes were taken, and the results after fitting for 12 mo were compared between the two groups.RESULTS: Multiple linear regression analysis showed that baseline age was significantly correlated with the changes of SE and AL(all P<0.01). After controlling baseline variables, the adjusted changes in SE for 12 mo after wearing glasses in the DIMS group and HAL group were -0.41±0.18 and -0.34±0.13 D, respectively(P<0.001); the changes of AL in the DIMS group and HAL group were 0.31±0.08 and 0.27±0.06 mm, respectively(P<0.001). Patients were divided into younger group(7-9 years old)and older group(10-12 years old). The changes in SE(t=2.250, P=0.025)and AL(t=3.120, P=0.002)of the younger group who wearing DIMS lens were greater than those with HAL after 12 mo, and the same was true in the older group(t=5.931, 5.033, both P<0.001).CONCLUSION: Under the condition of combined use of 0.01% atropine eye drops, HAL is more effective than DIMS lens in controlling myopia diopter and AL of adolescents.
7.Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis
Shuangshuang PENG ; Wei LI ; Zhaoya ZHOU ; Biao ZHANG ; Chaoshan WANG ; Xiaohong PU ; Wen YANG ; Jun YANG ; Hongyan WU ; Yao FU ; Jieyu CHEN ; Xiangshan FAN
Chinese Journal of Clinical and Experimental Pathology 2023;39(11):1328-1333
Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0%)and 3(8.3%)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5%)(P<0.001)and 9 cases(52.9%)(P=0.001)were present in mIMA.There were 5 cases(13.9%)of high nuclear grade of IMA and 10 cases(58.8%)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5%in IMA,but 60.0%and 80.0%in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6%,21.9%,and 9.4%,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100%,20%,20%and 100%,6.7%,6.7%,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0%(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7%(5/12)and 33.3%(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4%)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1%)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.
8.Chronic intestinal pseudo-obstruction as the initial manifestation of small cell lung carcinoma
Xintong WU ; Shuangshuang LU ; Bingjian WANG ; Xinyu YAO ; Wei ZHANG ; Junfang MA ; Shaohua ZHUANG ; Jian HUANG ; Yuzhou JIN ; Wenjia LIU
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):382-384
This article reports a case of small cell lung cancer with chronic intestinal pseudo-obstruction as the initial manifestation in the Changzhou No.2 People′s Hospital, and reviews relevant literature reports in order to improve clinicians′ understanding of paraneoplastic syndrome associated with small bowel obstruction and reduce missed diagnosis and misdiagnosis.
9.Chronic intestinal pseudo-obstruction as the initial manifestation of small cell lung carcinoma
Xintong WU ; Shuangshuang LU ; Bingjian WANG ; Xinyu YAO ; Wei ZHANG ; Junfang MA ; Shaohua ZHUANG ; Jian HUANG ; Yuzhou JIN ; Wenjia LIU
Chinese Journal of Inflammatory Bowel Diseases 2023;07(4):382-384
This article reports a case of small cell lung cancer with chronic intestinal pseudo-obstruction as the initial manifestation in the Changzhou No.2 People′s Hospital, and reviews relevant literature reports in order to improve clinicians′ understanding of paraneoplastic syndrome associated with small bowel obstruction and reduce missed diagnosis and misdiagnosis.
10.Establishment of Cryosectioning Method and Histochemical Localization Analysis of Volatile Oil and Coumarin Components of Ferula ferulaeoides
Yuanyuan ZHAO ; Ying MA ; Shuangshuang LIU ; Mengmeng LIU ; Xin LU ; Jiaqi YAO ; Siwei ZHANG ; Yun ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(13):161-166
ObjectiveTo establish the frozen section method of Ferula ferulaeoides, and to study the histochemical localization of volatile oil and coumarins in different organs of F. ferulaeoides. MethodThe roots, stems, petioles and leaves of F. ferulaeoides were used as materials to investigate the concentration of sucrose protectant, liquid nitrogen flash-freezing time, embedding conditions, section thickness, freezing temperature and time and post-treatment methods, the most suitable section conditions were screened by comparing the integrity, microscopic effect, elongation and clarity of frozen sections. Sudan Ⅳ staining method and fluorescence microscopy were used to locate the volatile oil and coumarins of F. ferulaeoides. ResultThe optimal conditions for frozen sections of the roots, stems, petioles and leaves of F. ferulaeoides were as follows:10%, 15% and 20% gradient sucrose as the protectant for roots, 10%, 20% and 30% gradient sucrose as the protectant for stems and petioles, 20%, 25% and 30% gradient sucrose as the protectant for leaves, glue-water (2∶1) as the embedding agent, quick-freeze in liquid nitrogen for 20 s, warmed up at -25 ℃ for 30 min, sliced at -20 ℃ with the thickness of 25 μm, rinsed with the same concentration of sucrose solution (gradient sucrose solution selected the last concentration), and the slices placed on the ice pack for a period of time and stored at room temperature. Among them, the concentration of sucrose protectant was the most important factor. The results of histochemical localization showed that volatile oil and coumarins in four organs of F. ferulaeoides were mainly distributed in resin canal. ConclusionFrozen section of F. ferulaeoides is established for the first time with high rate of slicing and simplified steps, its volatile oil and coumarins are mainly accumulated in resin canal.

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