1.Molecular biological research and molecular homologous modeling of Bw.03 subgroup
Li WANG ; Yongkui KONG ; Huifang JIN ; Xin LIU ; Ying XIE ; Xue LIU ; Yanli CHANG ; Yafang WANG ; Shumiao YANG ; Di ZHU ; Qiankun YANG
Chinese Journal of Blood Transfusion 2025;38(1):112-115
[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.
2.Effects of coal mine dust on lung function in rats
LIU Yang ; LI Meng ; LU Liyuan ; WANG Ru ; YANG He ; ZHANG Huifang
Journal of Preventive Medicine 2025;37(1):96-101
Objective:
To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis.
Methods:
Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting.
Results:
There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05).
Conclusion
The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.
3.Dapagliflozin on acute kidney injury and prognosis in patients with diabetes mellitus type 2 and acute coronary syndrome after percutaneous coronary intervention
Huifang HAO ; Xiufeng ZHAI ; Qing LI ; Shicheng YANG ; Peng ZHANG
China Pharmacy 2025;36(4):469-474
OBJECTIVE To investigate the impact of dapagliflozin on contrast-induced acute kidney injury (CIAKI) and prognosis in patients with diabetes mellitus type 2 (T2DM) and acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). METHODS Retrospective selection of data on T2DM patients with ACS who underwent PCI treatment in the Cardiology Department of Tianjin Chest Hospital from January 1st 2021 to December 31st 2022. The patients were divided into dapagliflozin group (96 cases) and control group (148 cases) based on whether they received dapagliflozin or not. Renal function indicators were measured for all enrolled patients before PCI and at 48 h and 1 week after PCI, including blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and β2-microglobulin (β2-MG). All patients were followed up for at least 1 year. The incidence of CIAKI and major adverse cardiac event (MACE) during follow-up were recorded for both groups. Logistic regression was used to analyze the impact of dapagliflozin on the occurrence of CIAKI, while the Log-rank test was applied to compare the incidence of MACE between the two groups. Cox regression was employed to analyze the impact of dapagliflozin on prognosis. RESULTS At 48 h and 1 week after PCI, serum levels of Cys-C, KIM-1 and β2-MG were significantly lower in the dapagliflozin group compared to the control group (P<0.05). The incidence of CIAKI was lower in the dapagliflozin group compared to the control group (6.25% vs. 14.86%, P=0.042). Logistic regression analysis revealed that dapagliflozin was an independent protective factor against CIAKI (OR=0.280, 95%CI 0.101-0.780,P=0.015). During the follow-up period, the incidence of MACE was lower in the dapagliflozin group compared to the control group (7.29% vs. 17.57%, P=0.049). Cox regression analysis indicated that dapagliflozin reduced the occurrence of MACE after PCI (HR=0.374, 95%CI 0.161-0.866, P=0.022). CONCLUSIONS With adequate hydration, the use of dapagliflozin does not increase the risk of CIAKI following PCI in T2DM patients with ACS.
4.Herbal Textual Research on Kochiae Fructus in Famous Classical Formulas
Huifang HU ; Liping YANG ; Fei CHEN ; Xiaohui MA ; Ling JIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):247-257
In this paper, by referring to ancient and modern literature, the textual research of Kochiae Fructus has been conducted to clarify the name, origin, distribution of production areas, quality specification, taste and efficacy, harvesting time, processing and compatibility taboo, so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation, it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic, and has been used as the official name throughout history. It is also known by other names such as Dimai, Dikui, and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia, which is consistent throughout history. In the Han dynasty, it was recorded that Kochiae Fructus was produced in Jingzhou(Hubei province), while modern literature records its distribution throughout the country, so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn, and the quality is best when it is full, gray green in color, and no impurities. There are two processing methods for its origin:from the Southern and Northern dynasties to the Ming dynasty, it was dried in the shade, and after the founding of the People's Republic of China, it was dried in the sun. There are few records about the processing of Kochiae Fructus, and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar, and the leaves are taken in April and May, processing in the place of origin is shade drying, the processing methods include burning ash and frying frost, pounding juice and wine soaking. For internal use, it is mostly decocted or mashed, while for external use, it is mostly washed with decoction or taken in a soup bath. Throughout history, it has been recorded that Kochiae Fructus is bitter and cold, and is mainly used for treating bladder fever. After the founding of the People's Republic of China, most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia, it has been recorded that Kochiae Fructus has a pungent and bitter taste, and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness, dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history, it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times, it has been used to regulate the liver, spleen and large intestine meridians, with functions such as clearing heat and detoxifying, and diuresis. Based on the textual research, it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus, and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements, the raw products is taken into medicine.
5.Herbal Textual Research on Cnidii Fructus in Famous Classical Formulas
Huifang HU ; Liping YANG ; Fei CHEN ; Xiaohui MA ; Ling JIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):243-253
In this paper, by referring to ancient and modern literature, the textual research of Cnidii Fructus has been conducted to clarify the name, origin, distribution of production areas, quality specification, nature and flavour, efficacy, harvesting and processing, compatibility taboo and others, so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research, it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic, the materia medica of all dynasties was named Shechuangzi, and there are also aliases such as Shesu, Shemi, and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri, and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty, the origin of Cnidii Fructus was Zibo, Shandong province. During the Five dynasties, it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province, the Song dynasty added Shangqiu in Henan province, and it was considered that Yangzhou, Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China, the origin is clearly distributed throughout the country. For its quality evaluation, generally full grain, gray yellow color, strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month, and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products, mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past, there were also stir-frying with honey, stir-frying with salt and rice wine, immersing and steaming with rice wine and other methods. In recent times, it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter, Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm, acted on the kidney meridian, and had small toxicity. After the founding of the People's Republic of China, most of the literature classified it as a medicine to attack poison, kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness, destroying parasites and elieving itching, warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research, it is suggested that when developing the famous classical formulas containing Cnidii Fructus, the source shall be the dried ripe fruit of C. monnieri, and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas, the raw products can be taken into medicine.
6.Impact of 0.05% cyclosporine eye drops on postoperative ocular surface recovery following pterygium excision with limbal stem cell transplantation
Huifang LIAN ; Qiuhong WEI ; Weisong MA ; Weina GAO ; Chu WANG ; Rong ZHANG ; Chengwen YANG ; Jingjing CAI
International Eye Science 2025;25(12):2056-2060
AIM: To evaluate the efficacy of 0.05% cyclosporine eye drops in promoting ocular surface recovery following pterygium excision combined with autologous corneal limbal stem cell transplantation.METHODS:This study is a prospective randomized controlled trial, selecting 104 cases(104 eyes)of primary pterygium with monocular onset admitted to Baoding First Central Hospital from September 2023 to September 2024 as the initial sample. The patients were divided into an experimental group and a control group using a random number table method, with 52 eyes in each group. Both groups underwent pterygium excision and autologous corneal limbal stem cell transplantation performed by the same surgeon. The control group received tobramycin dexamethasone eye drops combined with 0.3% sodium hyaluronate eye drops, while the experimental group was additionally treated with 0.05% cyclosporine eye drops. The corneal epithelial repair status, ocular surface function [corneal fluorescein staining(FL)score, Schirmer I test(SIt), break-up time of tear film(BUT)] at preoperative and postoperative time points(1 and 3 mo), and dry eye symptoms [ocular surface disease index(OSDI), standard patient evaluation of eye dryness(SPEED)scores]. Additionally, the recurrence rate and postoperative complications were recorded.RESULTS: During the follow-up period, there was 1 case of loss to follow-up in both the experimental group and the control group, with lost to follow-up rate of 1.9%. Finally, 51 cases in each group completed all followed-up. No statistically significant difference was observed in preoperative general characteristics of patients between the two groups(P>0.05), and there was no statistically significant difference in corneal epithelial repair time or suture removal time(all P>0.05). At 1 mo postoperatively, the SIt and BUT decreased in both groups compared to preoperative levels, with the experimental group showing higher values than the control group(all P<0.05). FL scores increased compared to preoperative levels but were lower in the experimental group(all P<0.05). By 3 mo, the SIt, BUT and FL score of the control group were not statistically different from preoperative levels(all P>0.05), whereas the experimental group showed increased SIt and BUT, which were higher than the control group, and reduced FL scores, and decreased FL scores, which was lower than the control group(all P<0.05). At 3 mo postoperatively, both groups showed increased SIt and BUT compared to 1-month values, with the experimental group outperforming the control group(all P<0.05). FL scores decreased in both groups compared to 1-month values, with the experimental group maintaining lower scores(P<0.05). At 1 mo postoperatively, OSDI and SPEED scores were higher than preoperative levels, with the experimental group higher than the control group(all P<0.05); at 3 mo postoperatively, the scores returned to preoperative level(all P>0.05), and the OSDI and SPEED scores of the control group increased and higher than those of the experiment group(all P<0.05); at 3 mo postoperatively, the OSDI and SPEED scores decreased when compared with 1-month preoperative level, and the experiment group was lower than the control group(all P<0.05). There was no difference in the total incidence of postoperative complications between the two groups(P>0.05). According to the statistics of 6 mo follow-up after operation, there was no recurrence in the experimental group, and the recurrence rate was 11.8% in the control group(P<0.05).CONCLUSION: Adjunctive use of 0.05% cyclosporine eye drops after pterygium excision with limbal stem cell transplantation enhances ocular surface recovery, reduces dry eye symptoms, and lowers recurrence rates without compromising corneal epithelial healing or safety.
7.Efficacy and safety of chimeric antigen receptor T cell therapy combined with zanubrutinib in the treatment of relapsed/refractory diffuse large B-cell lymphoma.
Langqi WANG ; Chunyan YUE ; Xuan ZHOU ; Jilong YANG ; Bo JIN ; Bo WANG ; Minhong HUANG ; Huifang CHEN ; Lijuan ZHOU ; Sanfang TU ; Yuhua LI
Chinese Medical Journal 2025;138(6):748-750
8.Modulating active targeting nanoparticle design according to tumor progressions.
Huifang NIE ; Rong HUANG ; Guangwei JIANG ; Wenshuai LI ; Lan YANG ; Meng ZHANG ; Min QIAN ; Wei GUO ; Tao YE ; Rongqin HUANG
Acta Pharmaceutica Sinica B 2025;15(2):1143-1158
Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.
9.Erratum: Author correction to "PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism" Acta Pharm Sin B 13 (2023) 157-173.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2025;15(4):2297-2299
[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].
10.CDH17-targeting CAR-NK cells synergize with CD47 blockade for potent suppression of gastrointestinal cancers.
Liuhai ZHENG ; Youbing DING ; Xiaolong XU ; Huifang WANG ; Guangwei SHI ; Yang LI ; Yuanqiao HE ; Yue GONG ; Xiaodong ZHANG ; Jinxi WEI ; Zhiyu DONG ; Jiexuan LI ; Shanchao ZHAO ; Rui HOU ; Wei ZHANG ; Jigang WANG ; Zhijie LI
Acta Pharmaceutica Sinica B 2025;15(5):2559-2574
Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.


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