1.Exploring Mechanism of Xiaoqinglongtang Against High Altitude Pulmonary Edema Based on Integrative Pharmacology Model
Rongrong WANG ; Chuchu WANG ; Qi XU ; Qin JIAN ; Junzhi LIN ; Ruli LI ; Chuan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):137-148
ObjectiveTo explore the potential mechanism of Xiaoqinglongtang(XQL) in the prevention and treatment of high altitude pulmonary edema(HAPE) by network pharmacology, molecular docking, and molecular dynamics simulation, and to verify it by in vivo animal model. MethodsIn this study, the active ingredients, drug targets, and HAPE-related targets of XQL were collected from BATMAN-TCM, GeneCards, and Online Mendelian Inheritance in Man(OMIM) databases. The protein-protein interaction(PPI) network was constructed by using intersection targets, and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part, a mouse model of HAPE induced by hypobaric hypoxia(simulated 6 000 m altitude for 48 h) was established. The control effect was evaluated by hematoxylin-eosin(HE) staining, lung tissue water content, lung tissue wet/dry weight ratio, real-time quantitative polymerase chain reaction(Real-time PCR) detection of gene expression levels, and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL, 2 142 targets, 716 HAPE-related targets, and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin (IL)-6, tumor necrosis factor (TNF), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α) were screened. The results of GO analysis of common targets involved 738 biological processes(BP), 72 cellular components(CC), and 135 molecular functions(MF). KEGG analysis effectively enriched two important signaling pathways: Phosphoinositol 3-kinase (PI3K)/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia(6 000 m, 48 h), the lung tissue water content, lung tissue wet/dry weight ratio, and pathological injury score of the model group were significantly increased(P<0.01), accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium, a significant increase in inflammatory cells, a significant widening of the alveolar septum, and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes(P<0.01). The results of inflammatory factor expression showed that compared with the control group, the model group showed significantly up-regulated expression of TNF-α, IL-6, and IL-1β in the lung tissue(P<0.01). Compared with the model group, the XQL administration group had significantly decreased expression of inflammatory factors(P<0.05, P<0.01). The mRNA expression of key pathway related genes PI3K, Akt1, mammalian target of rapamycin(mTOR), and HIF-1α was significantly increased in the model group(P<0.01), and decreased in a concentration-dependent manner after XQL administration(P<0.05, P<0.01). The expression levels of key proteins PI3K, phosphorylation(p)-PI3K, Akt1, p-Akt1, mTOR, p-mTOR, and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group, the model group showed increased expression of key proteins(P<0.05, P<0.01). Compared with the model group, the XQL administration group exhibited decreased expression of key proteins(P<0.05, P<0.01). ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.
2.Exploring Mechanism of Xiaoqinglongtang Against High Altitude Pulmonary Edema Based on Integrative Pharmacology Model
Rongrong WANG ; Chuchu WANG ; Qi XU ; Qin JIAN ; Junzhi LIN ; Ruli LI ; Chuan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):137-148
ObjectiveTo explore the potential mechanism of Xiaoqinglongtang(XQL) in the prevention and treatment of high altitude pulmonary edema(HAPE) by network pharmacology, molecular docking, and molecular dynamics simulation, and to verify it by in vivo animal model. MethodsIn this study, the active ingredients, drug targets, and HAPE-related targets of XQL were collected from BATMAN-TCM, GeneCards, and Online Mendelian Inheritance in Man(OMIM) databases. The protein-protein interaction(PPI) network was constructed by using intersection targets, and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part, a mouse model of HAPE induced by hypobaric hypoxia(simulated 6 000 m altitude for 48 h) was established. The control effect was evaluated by hematoxylin-eosin(HE) staining, lung tissue water content, lung tissue wet/dry weight ratio, real-time quantitative polymerase chain reaction(Real-time PCR) detection of gene expression levels, and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL, 2 142 targets, 716 HAPE-related targets, and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin (IL)-6, tumor necrosis factor (TNF), protein kinase B1 (Akt1), and hypoxia-inducible factor-1α (HIF-1α) were screened. The results of GO analysis of common targets involved 738 biological processes(BP), 72 cellular components(CC), and 135 molecular functions(MF). KEGG analysis effectively enriched two important signaling pathways: Phosphoinositol 3-kinase (PI3K)/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia(6 000 m, 48 h), the lung tissue water content, lung tissue wet/dry weight ratio, and pathological injury score of the model group were significantly increased(P<0.01), accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium, a significant increase in inflammatory cells, a significant widening of the alveolar septum, and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes(P<0.01). The results of inflammatory factor expression showed that compared with the control group, the model group showed significantly up-regulated expression of TNF-α, IL-6, and IL-1β in the lung tissue(P<0.01). Compared with the model group, the XQL administration group had significantly decreased expression of inflammatory factors(P<0.05, P<0.01). The mRNA expression of key pathway related genes PI3K, Akt1, mammalian target of rapamycin(mTOR), and HIF-1α was significantly increased in the model group(P<0.01), and decreased in a concentration-dependent manner after XQL administration(P<0.05, P<0.01). The expression levels of key proteins PI3K, phosphorylation(p)-PI3K, Akt1, p-Akt1, mTOR, p-mTOR, and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group, the model group showed increased expression of key proteins(P<0.05, P<0.01). Compared with the model group, the XQL administration group exhibited decreased expression of key proteins(P<0.05, P<0.01). ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.
3.Clinical comprehensive evaluation of four Chinese patent medicines in the treatment of hyperlipidemia
Mingzhu ZHANG ; Yizhuo QIN ; Xianshuai TANG ; Lei ZHENG ; Jinfang SONG
China Pharmacy 2026;37(6):708-712
OBJECTIVE To evaluate the clinical comprehensive value of four Chinese patent medicines (Xuezhikang, Zhibitai, Zhibituo, Jiangzhiling) in the treatment of hyperlipidemia, and provide a reference for rational clinical drug use. METHODS A clinical comprehensive evaluation index system was established in accordance with the Evidence and Value: Impact on Decision-Making (EVIDEM) framework and Technical Guideline for Clinical Comprehensive Evaluation of Cardiovascular Drugs (2022 edition, trial implementation). CNKI, Wanfang data, VIP, PubMed, ScienceDirect, Embase and official websites were retrieved to collect the literature such as drug instructions, guidelines and consensus statements, and systematic reviews/meta-analyses for the four Chinese patent medicines. A comprehensive evaluation was conducted from seven dimensions: effectiveness, safety, economy, suitability, accessibility, innovation and characteristics of traditional Chinese medicine. RESULTS This evaluation index system included 7 first-level indicators, 15 second-level indicators and 30 third-level indicators. Xuezhikang achieved the highest comprehensive evaluation score of 81.4 points, and was classified as class Ⅰ recommendation. Zhibitai with 76.0 points and Zhibituo with 60.9 points were both classified as class Ⅱ recommendation. Jiangzhiling with 48.8 points was classified as class Ⅳ recommendation. CONCLUSIONS Xuezhikang demonstrates the optimal clinical comprehensive value for treating hyperlipidemia. Zhibitai exhibits certain advantages in terms of safety and characteristics of traditional Chinese medicine; Zhibituo shows a moderate performance in all aspects; Jiangzhiling has a relatively low score. Appropriate medicines can be selected clinically according to actual conditions and patients’ characteristics.
4.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
5.Transverse dimensional changes following Twin-Block and slow maxillary expansion therapy in adolescents with Angle Class Ⅱ division 1 malocclusion: a cone-beam computed tomography study
PAN Yinti ; QIN Changtao ; ZHENG Yi ; GUO Anjie ; SUN Xin ; CHEN Zhixing ; MO Shuixue
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(5):471-482
Objective:
To investigate the effects of a Twin-Block appliance combined with slow maxillary expansion (SME) on transverse dental and skeletal parameters in adolescent patients with Angle Class Ⅱ division 1 malocclusion, and to provide a reference for clinical orthodontic practice.
Methods:
This retrospective study was approved by the Institutional Ethics Committee. A total of 21 adolescents with Class Ⅱ division 1 malocclusion who underwent two-phase treatment with a Twin-Block appliance combined with SME at the Department of Orthodontics, College & Hospital of Stomatology, Guangxi Medical University, in 2021 to 2023 were consecutively enrolled. In the first phase, a functional appliance was used to coordinate the skeletal relationship between the maxilla and mandible by leveraging growth potential. In the second phase, a fixed appliance was employed for fine adjustments of the dental arches based on the specific condition. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T0) and after the first phase of functional correction (T1). Transverse measurements at the first molar region, including molar buccolingual inclination, dental arch width, and basal bone width, were performed using Dolphin 3D Imaging software. Changes between T0 and T1 were statistically analyzed.
Results:
After the first phase of treatment, the left and right maxillary first molars showed a significant increase in buccal inclination by 5.47° ± 1.38° and 5.35° ± 1.61°, respectively (P<0.001). The arch width in the maxillary first molar region also increased by (2.68 ± 1.14) mm, and the basal bone width increased by (1.14 ± 1.24) mm (all P<0.001). The proportion of skeletal expansion accounted for an average of 42.86%, while dental expansion accounted for 57.14%. No statistically significant changes were observed in any mandibular transverse measurements (all P>0.05).
Conclusion
In adolescent patients with Angle Class Ⅱ division 1 malocclusion accompanied by maxillary transverse deficiency, Twin-Block appliance combined with SME can effectively expand maxillary dental arch and basal bone width while improving sagittal relationship, thereby correcting transverse discrepancy. The maxillary width changes were predominantly dental.
6.Protective effect of modified University of Wisconsin preservation solution containing α 2-adrenergic receptor agonists and noble gases on isolated amputated skeletal muscle of rats
Zhengwei XUE ; Zhigang QIN ; Xiangfeng LIU ; Jieyu LI ; Ling JIANG ; Xiao LI ; Jianbo MA ; Guanlei LIU ; Pengfei ZHENG ; Ying TANG ; Peng LI ; Jianteng GU
Chinese Journal of Trauma 2025;41(11):1112-1122
Objective:To develop a modified University of Wisconsin preservation solution (UW solution) containing α 2-adrenergic receptor agonists (dexmedetomidine) and noble gases (argon) and investigate its protective effect on the isolated amputated skeletal muscle of rats. Methods:Sixty male SD rats were selected to establish a hindlimb cold preservation/perfusion model and were divided into blank control group, hypothermic storage group, UW solution perfusion group, and modified UW solution perfusion group using a random number table, with 15 rats in each group. Simultaneously, a cold preservation model of rat skeletal muscle myoblasts (L6 cells) was established and the rats were also divided into four groups in the same way. Animal models were prepared in different ways: In the blank control group, the hindlimbs received no special treatment; In the hypothermic storage group, the amputated hindlimbs were stored in a dry centrifuge tube at 4℃ for 18 hours; In the UW solution perfusion group, the amputated hindlimbs were perfused with UW solution and then stored in a centrifuge tube containing UW solution at 4℃ for 18 hours; In the modified UW solution perfusion group, the amputated hindlimbs were perfused with modified UW solution (containing 0.1 nmol/L dexmedetomidine and 50% volume fraction of argon) and then stored in a centrifuge tube containing the modified UW solution at 4℃ for 18 hours. Cell models were treated as follows: In the blank control group, L6 cells were cultured under standard conditions; In the hypothermic storage group and UW solution group, L6 cells were treated with conventional culture medium or UW solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours; In the modified UW solution group, L6 cells were treated with the modified solution, stored in argon-filled sealed bags at 4℃ for 8 hours, and then rewarmed and cultured for 6 hours. After sample collection, skeletal muscle morphology, tissue edema and ultrastructure features were assessed by HE staining, wet-to-dry weight ratio, and transmission electron microscopy, respectively. Additionally, L6 cell morphology was examined by light microscopy. L6 cell viability was determined by cell counting kit-8 (CCK-8) assay (expressed as absorbance A value). Expression levels of glutathione peroxidase 4 (GPX4) protein in both skeletal muscle tissue and L6 cells were evaluated by immunofluorescence staining and Western blot, respectively.Results:After 18 hours of in vitro preservation of rat isolated amputated limbs, the following results were obtained: (1) HE staining results showed that the muscle fiber morphology of the modified UW solution perfusion group was close to that of the blank control group. Moreover, the area ratio of skeletal muscle cells in the modified UW solution perfusion group was significantly higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). (2) The wet-dry weight ratio results showed that there was no statistically significant difference among the modified UW solution perfusion group, the blank control group and UW solution group ( P>0.05), with significantly lower ratios in all three groups than that in the hypothermic storage group ( P<0.05). (3) Transmission electron microscopy results revealed that the modified UW solution perfusion group showed no statistically significant differences in ultrastructural metrics, including myofiber diameter, sarcomere length, mitochondrial short-axis/long-axis ratio, and mitochondrial cristae count, compared with those in the blank control group ( P>0.05), and performed significantly better than both the hypothermic storage group and UW solution perfusion group ( P<0.05). (4) Morphological observation of L6 cells showed that the cellular morphology was regular in the modified UW solution perfusion group, close to that in the blank control group, while it was severely damaged in the hypothermic storage group. Moreover, the cells were reduced in number and partially damaged in the UW solution group. The sequence of cell viability expressed as absorbance A value was blank control group >modified UW solution perfusion group > UW solution perfusion group > hypothermic storage group, with statistically significant differences among the four groups ( P<0.05). (5) Immunofluorescence staining showed that there was no statistically significant difference in fluorescence intensity of GPX4 protein expression between the modified UW solution perfusion group and blank control group ( P>0.05), while the fluorescence intensity was higher in the modified UW solution perfusion group than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Western blot analysis showed that the relative expression level of GPX4 in the modified UW solution group was significantly lower than that in the blank control group ( P<0.05), but higher than that in the hypothermic storage group and UW solution perfusion group ( P<0.05). Conclusion:The modified UW solution can stabilize the expression level of GPX4 protein, thereby inhibiting ferroptosis and alleviating cold preservation injury in both rat amputated isolated limb skeletal muscle tissue and L6 cells.
7.Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries (version 2025)
Fulin TAO ; Jinlei DONG ; Gang WANG ; Xianzhong MA ; Guanglin WANG ; Jiandong WANG ; Zhanying SHI ; Wei FENG ; Shiwen ZHU ; Gang LYU ; Guangyao LIU ; Dahui SUN ; Yuqiang SUN ; Ming LI ; Weixu LI ; Yan ZHUANG ; Kaifang CHEN ; Dapeng ZHOU ; Qishi ZHOU ; Zhangyuan LIN ; Chengla YI ; Longpo ZHENG ; Jianzhong GUAN ; Zhiyong HOU ; Shuquan GUO ; Xiaodong GUO ; Xiaoshan GUO ; Xiaodong QIN ; Hua CHEN ; Shicai FAN ; Dongsheng ZHOU ; Lianxin LI
Chinese Journal of Trauma 2025;41(8):709-720
Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.
8.Bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma: a multicenter retrospective study
Shuchao QIN ; Yi MIAO ; Zhaoliang ZHANG ; Jie ZHANG ; Yuye SHI ; Yuqing MIAO ; Weiying GU ; Weicheng ZHENG ; Zhuxia JIA ; Guoqiang LIN ; Haiwen NI ; Xiaohong XU ; Min XU ; Xiaoyan XIE ; Ling WANG ; Yun ZHUANG ; Wei ZHANG ; Ping LIU ; Jianyong LI ; Wenyu SHI
Chinese Journal of Hematology 2025;46(9):820-826
Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.
9.Association between genotype and phenotype in children with Phenylalanine hydroxylase deficiency in Lianyungang area
Shuang LIU ; Qin ZHENG ; Dandan CUI ; Wei WANG ; Leilei WANG ; Guanghua LUO
Chinese Journal of Medical Genetics 2025;42(6):648-659
Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.
10.Evaluating the effectiveness of a primary care general practitioner rotation training program based on three core competencies
Wei ZHOU ; Weilin LI ; Peihong LIU ; Beibei QIN ; Xinting ZHENG ; Xinyi MEI
Chinese Journal of General Practitioners 2025;24(10):1240-1245
Objective:To evaluate the effectiveness of a rotation training program for primary care general practitioners (GPs) in Taizhou, China, designed around three core competencies.Methods:A longitudinal study was conducted. A total of 111 primary care GPs participating in the 1st to 5th sessions of the Taizhou GP rotation training program at Taizhou Hospital (the designated training center) in Zhejiang Province from July 2022 to December 2024 were included. Based on the World Organization of Family Doctors (WONCA) competency model, combined with literature review and expert consultation, 15 potential training components were identified. A needs assessment survey among primary care GPs was then conducted, leading to the finalization of three core competencies for the training: ①Evidence-based management of common diseases, frequently-occurring diseases, and common symptoms; ②Early identification, management, and referral of critically ill patients; ③Chronic disease management and health promotion capabilities. A 4-month full-time immersion training program was structured around these competencies, comprising three phases: theoretical training (1 week), clinical comprehensive skills training (14 weeks), and primary care practice training (1 week). Assessments included a pre-and post-training theoretical knowledge test and a final clinical assessment. The final assessment utilized a three-station Objective Structured Clinical Examination (OSCE) evaluating patient consultation, clinical reasoning & decision-making, and clinical procedural skills. A self-administered satisfaction survey was also distributed post-training.Results:The 111 participants were predominantly aged 30-49 years (72.1% (80/111)), held bachelor′s degrees (87.4% (97/111)), were licensed physicians (78.4% (87/111)), and had junior or intermediate professional titles (87.4% (97/111)). Post-training theoretical scores were significantly higher than pre-training scores (76.26±7.00 vs. 69.94±6.40, t=-10.45, P<0.001). All participants 100%(111/111) passed the final OSCE assessment. The mean scores for the OSCE stations were: patient consultation 85.99±7.30, clinical reasoning & decision-making 82.72±7.61, and clinical procedural skills 89.60±5.65. Satisfaction rates were 100.0% (111/111) for the overall program, the three-phase design, the core competency training content, theoretical training, clinical skills training, and clinical rotation departments. Satisfaction was 98.2% (109/111) for the 4-month full-time duration, 99.1% (110/111) for the "2+X" clinical rotation model (2 weeks each in General Practice and Emergency Medicine+elective rotations in 4 other departments), and 97.3% (108/111) for the primary care practice base. Conclusions:The competency-based rotation training program for primary care GPs in Taizhou effectively enhanced participants′ theoretical knowledge and clinical practical skills, and achieved high levels of participant satisfaction. This model offers valuable insights for optimizing primary care GP training in similar settings.


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