1.Network meta-analysis of the efficacy and safety of dual amoxicillin-based regimens for Helicobacter pylori eradication
Ziwen SONG ; Xinmiao YUAN ; Liyuan LUO ; Yufang HE ; Lingshu YANG ; Yixu HUANG ; Jianpeng SHE ; Peihan WEI ; Sihan GUO ; Fei DUAN
China Pharmacy 2026;37(8):1074-1079
OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) for Helicobacter pylori (Hp) eradication. METHODS Randomized controlled trial (RCTs) on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and VIP data. The search time frame was from database inception to September 5, 2025. After literature screening, data extraction, and quality assessment, a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included, encompassing 8 therapeutic regimens: PPI combined with high-dose amoxicillin for 14 days (TR1), PPI combined with low-dose amoxicillin for 14 days (TR2), P-CAB combined with high-dose amoxicillin for 7 days (TR3), P-CAB combined with high-dose amoxicillin for 14 days (TR4), P-CAB combined with high-dose amoxicillin for 10 days (TR5), P-CAB combined with low-dose amoxicillin for 7 days (TR6), P-CAB combined with low-dose amoxicillin for 14 days (TR7), and P-CAB combined with low-dose amoxicillin for 10 days (TR8). The network meta-analysis results showed that, in terms of intention-to-treat Hp eradication rates, the eradication rates of TR5 and TR4 were significantly higher than those of TR3, TR8, TR6 and TR1 ( P <0.05). The surface under the cumulative ranking curve (SUCRA) values from highest to lowest were: TR4 (89.7%)>TR5 (82.3%)>TR7 (71.5%)> TR2 (48.6%)>TR1 (43.9%)>TR8 (28.7%)>TR3 (22.7%)>TR6 (12.6%). Regarding safety, the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 ( P <0.05). The SUCRA values from highest to lowest were: TR1 (91.3%)>TR4 (79.8%)>TR5 (55.0%)>TR7 (50.9%)>TR8 (41.3%)>TR2 (36.4%)>TR3 (27.6%) >TR6 (17.7%). CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy, the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.
2.Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain
Jiao LI ; Qi LI ; Shuang CHENG ; Jiayi SONG ; Xiaohui GUO ; Xiang WANG ; Di CHENG ; Kefeng FAN ; Ju WANG
Journal of Environmental and Occupational Medicine 2026;43(4):475-484
Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11+0 to 13+6 weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35+0 to 37+6 weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L−1, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g−1 (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.
3.Mechanisms of Antidepressant Effect of Zhizi Houpotang and Its Herbal Pairs Based on NLRP3/GSDMD Signaling Pathway
Chang CHEN ; Ziwen GUO ; Tingyu SONG ; Yan WANG ; Baomei XIA ; Weiwei TAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):72-80
ObjectiveTaking classical herbal pair compatibility research as the entry point, this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine (TCM) formula Zhizi Houpotang, and to elucidate its antidepressant mechanism, with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group, a chronic unpredictable mild stress (CUMS) depression model group, a Zhizi Houpotang full-formula group (6 g·kg-1·d-1), a Magnoliae Officinalis Cortex (MOC)-Aurantii Fructus Immaturus (AFI) herbal pair group (4.2 g·kg-1·d-1), a Gardeniae Fructus (GF)-MOC herbal pair group (4.2 g·kg-1·d-1), a GF-AFI herbal pair group (3.6 g·kg-1·d-1), and a positive drug group (fluoxetine, 12 mg·kg-1·d-1). Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 (Ibal) and the purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) in the prefrontal cortex (PFC). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 (Panx1), P2RX7, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, GSDMD, postsynaptic density protein 95 (PSD95), and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group, the depression model group exhibited significant depressive-like behaviors. In addition, the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased (P<0.01), the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated (P<0.01), and the protein expression levels of Panx1, P2RX7, NLRP3, ASC, Caspase-1, and GSDMD in the PFC were significantly upregulated (P<0.01). In contrast, the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated (P<0.01), and neuronal dendritic spine density was significantly reduced (P<0.01). Compared with the model group, the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators (P<0.01). The GF-AFI herbal pair group improved all the above indicators except P2RX7, Caspase-1, GSDMD, and PSD95 (P<0.05, P<0.01). In contrast, the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair, GF-MOC, can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling, thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously, it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density, promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula, and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.
4.Phenotypic distribution and population genetic frequency analysis of ABO and Rh blood group antigens among voluntary blood donors in Yantai
Hewei SONG ; Xiaojun ZHANG ; Qun XU ; Xiangzhong LIU ; Nan GUO ; Di SUN
Chinese Journal of Blood Transfusion 2026;39(1):69-75
Objective: To investigate the distribution characteristics of ABO and Rh blood group antigen phenotypes among blood donors in the Yantai, Shandong. Methods: Blood samples from 310 180 voluntary blood donors in Yantai collected from January 2019 to December 2023 were tested for ABO and Rh blood group antigens using standard serological methods. RhD-negative samples were further typed for C, c, E, and e antigens. Population genetic analysis of blood groups was performed: allele frequencies were inferred from ABO phenotypes, and Rh allele/haplotype frequencies were estimated based on the proportion of RhD-negative donors and CcEe antigen typing, followed by Hardy-Weinberg equilibrium testing. Results: The phenotypic distribution frequency of ABO blood groups was B(32.72%)>O(28.93%)>A(27.65%)>AB(10.70%). The inferred allele frequencies were r(53.74%)>q(24.78%)>p(21.48%), consistent with Hardy-Weinberg equilibrium (P>0.05). A total of 1 872 Rh-negative donors (0.603%) were identified. The most common Rh phenotypes were ccdee (59.56%) and Ccdee (30.18%). The distribution of Rh antigen phenotypes deviated significantly from Hardy-Weinberg equilibrium (χ
=37.15, P<0.001), with the cde haplotype showing the highest frequency. There was no statistically significant difference in ABO blood group distribution between RhD-positive and RhD-negative donors (P>0.05). Conclusion: The ABO blood group distribution among voluntary blood donors in Yantai is generally stable and consistent with population genetic equilibrium, whereas the Rh antigen phenotype distribution deviates from equilibrium, indicating potential underlying genetic structural differences.
5.Analysis of the changes in intestinal microbiota of patients with moderate to severe acne based on 16S rRNA high-throughput sequencing technology
Shichao JIANG ; Xiaomeng WANG ; Zheng CHEN ; Song QIAO ; Fan YANG ; Birong GUO
Acta Universitatis Medicinalis Anhui 2026;61(1):98-103
ObjectiveTo explore the relationship between acne vulgaris and gut microbiota. MethodsA total of 29 clinical cases diagnosed with moderate-to-severe acne vulgaris and 26 healthy individuals as control subjects were recruited. Fecal specimens were collected from all participants, and further analysis of gut microbial communities was performed by leveraging high-throughput sequencing techniques that target the hypervariable regions of 16S rRNA genes. ResultsAssociations between acne vulgaris and alterations in gut microbiota were identified. At the phylum level, the relative abundance of Bacteroidota exhibited a statistically significant elevation in the acne vulgaris cohort when compared with the healthy control group (P<0.01), while Cyanobacteria was significantly lower in the acne group (P<0.01). At the genus level, the top five different bacterial taxa in both groups were Bacteroides, Escherichia⁃Shigella, Klebsiella, Roseburia, and Parabacteroides. Among them, Bacteroides, Roseburia, and Parabacteroides were more abundant in acne patients. Linear discriminant analysis identified five biomarkers all belonging to the Bacteroidota phylum in the acne and control groups. These biomarkers belong to the phylum Bacteroidetes. ConclusionThere are significant differences in the composition of intestinal microbiota between acne patients and healthy people. Changes in the richness of specific bacterial genera may become new targets for the diagnosis and treatment of acne.
6.Effect of mussel-derived antimicrobial peptide-coated modified prosthesis on prevention of early periprosthetic joint infection and regulation of bone transfer
Bo LIU ; WUHUZI·WULAMU ; Guangzhao ZHU ; Xiaobin GUO ; Ziyue SONG ; Xingbu MENG ; Junjie HU ; Xiaogang ZHANG
Chinese Journal of Tissue Engineering Research 2026;30(2):278-287
BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.
7.Effect of mussel-derived antimicrobial peptide-coated modified prosthesis on prevention of early periprosthetic joint infection and regulation of bone transfer
Bo LIU ; WUHUZI·WULAMU ; Guangzhao ZHU ; Xiaobin GUO ; Ziyue SONG ; Xingbu MENG ; Junjie HU ; Xiaogang ZHANG
Chinese Journal of Tissue Engineering Research 2026;30(2):278-287
BACKGROUND:Periprosthetic joint infection is the most common cause of early failure after total knee replacement.The current methods of preventing periprosthetic joint infection by improving the surface of the prosthesis have limitations to varying degrees.OBJECTIVE:To construct a coating material that can stably improve the surface of the implant,prevent the initial floating bacterial infection of periprosthetic infection,and regulate the bone transfer function around the implant.METHODS:(1)Material preparation:YGF polypeptide(which promotes bone formation),LL-37 polypeptide(with antibacterial properties)and YGF+LL-37 composite peptide were prepared by Fmoc solid phase peptide synthesis technology.The titanium-based materials were immersed in the three polypeptide solutions for 2 hours to obtain YGF coating,LL-37 coating and composite peptide coating coated titanium sheets.(2)In vitro experiment:Uncoated titanium sheets and coated titanium sheets were co-cultured with Escherichia coli(or Staphylococcus aureus)and the colonies were counted by plate method.MC3T3 cells were inoculated on the surface of uncoated titanium sheet and coated titanium sheet,respectively.Alizarin red staining was used to observe the calcium salt deposition on the surface of the material.Western blot assay was used to detect the protein expression of RUNX2,osteocalcin,osteopontin,and bone morphogenetic protein 2.(3)Animal experiment:24 SD rats were randomly divided into three groups:the blank group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal;the control group(n=8)was implanted with uncoated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension;the experimental group(n=8)was implanted with composite peptide coated titanium nails in the femoral medullary canal+intra-articular injection of Staphylococcus aureus suspension.After 5 weeks of implantation,micro-CT examination,hematoxylin-eosin staining and immunohistochemical staining of femur specimens were performed.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with uncoated titanium sheet and YGF coated titanium sheet,LL-37 coated and composite peptide coated titanium sheet could significantly inhibit the growth and reproduction of Escherichia coli and Staphylococcus aureus.Compared with uncoated titanium sheets and LL-37-coated titanium sheets,YGF-coated and composite peptide-coated titanium sheets could promote calcium salt deposition in osteoblasts and increase the protein expression of RUNX2,osteocalcin,osteopontin and bone morphogenetic protein 2.(2)Animal experiment:Micro-CT test showed that the control group had less bone mass than the blank group and the experimental group.Hematoxylin-eosin staining showed that there was a large amount of fibrous tissue around the nail channel in the control group,only a small amount of tissue fibrosis around the nail channel in the blank group,and only a small amount of tissue fibrosis around the nail channel in the experimental group.Immunohistochemical staining showed that the protein expression of interleukin 1β and tumor necrosis factor α in the control group was higher than that in the blank group and the experimental group,and the expression of osteocalcin,RUNX2 and osteopontin in the experimental group was higher than that in the blank group and the control group.(3)The results show that the titanium-based material coated with YGF+LL-37 composite peptide coating has good antibacterial ability and can promote bone transfer around the implant.
8.Association between warning signs of psychological and behavioral development problems with emotional and behavioral problems in preschool children
LUO Meifang, SONG Qiying, ZHAO Xiaoli, GUO Yuqin, ZOU Li
Chinese Journal of School Health 2026;47(5):661-665
Objective:
To explore the association between warning signs of psychological and behavioral development problems with emotional and behavioral problems in preschool children in Bao an District, Shenzhen, so as to provide an empirical basis for optimizing psychological screening strategies in kindergartens.
Methods:
From September 2023 to August 2024, a total of 49 804 preschool children aged 4-6 years from all 401 kindergartens in Bao an District were enrolled as study subjects. The Warning Signs Checklist for Screening Psychological, Behavioral and Developmental Problems of Children and the parent version of the Strengths and Difficulties Questionnaire (SDQ) were used to assess children s developmental status and emotional and behavioral problems, respectively. Multivariable Logistic regression analysis was used to examine the association between warning signs and emotional and behavioral problems, stratified by sex.
Results:
The overall positive screening rate for developmental warning signs was 1.5%, and the detection rate for high risk in the SDQ total difficulties score was 6.3%. Multivariable Logistic regression analysis revealed that after adjusting for age, children who screened positive for warning signs exhibited a significantly higher risk of elevated SDQ total difficulties and subscale scores compared to those who screened negative, across both sexes (a OR boys =1.66-13.42, a OR girls =2.04-22.15, all P <0.01). The only exceptions were gross motor skills and conduct problems in boys, and personal social skills and conduct problems in girls. Notably, abnormalities in the personal social domain demonstrated the strongest association with emotional/behavioral problems (a OR boys =7.72-13.42, a OR girls =3.88-22.15), followed by the language domain (a OR boys =4.63-9.23, a OR girls =3.78-14.41) (all P <0.01).
Conclusion
A positive screening result for warning signs, particularly in the personal social and language domains, serves as a strong indicator of emotional and behavioral problems in preschool children.
9.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
10.The Effects of Qufeng Tongqiao Cough-Relieving Decoction (祛风通窍止咳方) on Cough Sensitivity,TRPV4 in Lung and Nasal Mucosal Tissues,and Neurogenic Inflammation in a Guinea Pig Model of Upper Airway Cough Syndrome
Jingshu LUO ; Jianling MA ; Liqing SHI ; Kun JI ; Song LIU ; Yuhan FAN ; Xianli LI ; Zhaodi GUO
Journal of Traditional Chinese Medicine 2025;66(5):518-525
ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction (祛风通窍止咳方, QTCD) in the treatment of upper airway cough syndrome (UACS). MethodsTwenty-four guinea pigs were randomly divided into blank group, model group, traditional Chinese medicine (TCM) group, and inhibitor group, with six guinea pigs in each group. Except for the blank group, guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection, followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling, the TCM group was administered QTCD 0.9 g/(100 g·d) by gavage, the inhibitor group received the transient receptor potential vanilloid receptor 4 (TRPV4) inhibitor GSK2193874 1 mmol/L, 5 min by nebulisation, and the blank group and model group were given 2 ml/(100 g·d) normal saline by gavage once daily. After 7 days of treatment, a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8) in serum, bronchoalveolar lavage fluid (BALF), and nasal lavage fluid (NLF) were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the protein levels of TRPV4, substance P (SP), and calcitonin gene-related peptide (CGRP) in lung and nasal mucosal tissues. Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of TRPV4, SP, and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group, while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group, the model group showed increased cough frequency, serum IgE level, and IL-6 and IL-8 levels in serum, BALF, and NLF. The protein levels of TRPV4, SP, and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated (P<0.05 or P<0.01). Compared with the model group, the TCM group and inhibitor group showed reduced cough frequency, serum IgE level, and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum, BALF, and NLF, reduced IL-6 in BALF, reduced IL-8 in NLF, and decreased TRPV4, SP, and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues (P<0.05 or P<0.01). Compared with the TCM group, the inhibitor group had increased serum IgE, IL-6, and IL-8 levels, increased IL-6 level in BALF, and increased IL-8 levle in NLF, but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues (P<0.01). ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway, improving airway neurogenic inflammation, alleviating inflammatory responses, and reducing cough hypersensitivity.


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