1.Meta-analysis of the efficacy and safety total glucosides of paeonia in the treatment of systemic lupus erythematosus
Xiangyan HAO ; Jiahui LENG ; Zhengqi LIU ; Xinchang WANG ; Cong HUANG ; Xiaopeng LI ; Yi LING
China Pharmacy 2026;37(2):232-237
OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia (TGP) in the treatment of systemic lupus erythematosus (SLE). METHODS Randomized controlled trial (RCT) about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Data, and CBM. The search period spanned from the inception of each database to June 1, 2025. After literature screening, data extraction, and quality assessment of the included studies, Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs, involving 1 318 patients, were included. Meta-analysis results showed that compared with western medicine alone, TGP combined with western medicine significantly improved clinical efficacy [OR=4.96, 95%CI(3.41, 7.23), P<0.000 01], complement 3 [MD=0.18, 95%CI (0.13, 0.23), P<0.000 01] and complement 4[MD=0.08, 般021) 95%CI (0.04, 0.11), P<0.000 01], and reduced the levels of immunoglobulin G (IgG) [MD=-3.10, 95%CI (-3.59,-2.62), P<0.000 01], IgA [MD=-0.68, 95%CI (-0.78, -0.58), P<0.000 01], IgM [MD=-0.43, 95%CI (-0.53,-0.34), P<0.000 01], systemic lupus erythematosus disease activity index (SLEDAI) [MD=-1.59, 95%CI (-2.20, -0.99), P<0.000 01], recurrence rate [OR=0.23, 95%CI (0.13, 0.42), P<0.000 01] and the incidence of adverse drug reactions [OR= 0.54, 95%CI (0.36, 0.82), P=0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients, promote the restoration of immunoglobulins and complements, reduce SLEDAI and recurrence rate and has good safety.
2.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
3.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
4.Consistent Detection of Aquaporin-4 Antibodies:A Comparative Analysis Between Fixed and Live Cell-Based Assays
Jing WANG ; Linge WANG ; Xiaolin YANG ; Zhizhong LI ; Jinyu JIANG ; Qiao XU ; Siyuan HUANG ; Qing FU ; Yang YANG ; Rongrong ZHANG ; Lin YANG ; Ai CHEN ; Xiaopeng ZENG ; Ke XU ; Peng ZHENG ; Xinyue QIN ; Jinzhou FENG
Journal of Clinical Neurology 2026;22(2):212-220
Background:
and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease.
Methods:
We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients.
Results:
Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups.
Conclusions
Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.
5.Mining Candidate Genes for Litter Size Traits in English Springer Spaniel Bitches Based on Whole Genome Resequencing
Yilong GAO ; Xingliang HE ; Xiaopeng ZHOU ; Dawei LI ; Xijun BAO ; Laiyou LI
Laboratory Animal and Comparative Medicine 2026;46(3):378-387
ObjectiveCandidate genes related to the regulation of litter size traits in English Springer Spaniel breeding bitches are explored, and the genetic mechanism underlying fertility in this breed is investigated, in order to provide reference molecular markers for genomic selection of high fecundity. MethodsWhole genome resequencing was performed on English Springer Spaniel breeding bitches that had given birth to at least 3 litters, and the bitches were divided into a high-litter-size group and a low-litter-size group according to the average litter size. Selection signal analysis was used to obtain the intersection of fixation index (Fst) and nucleotide diversity (Pi) signals as highly selected regions, and candidate genes were screened based on gene annotation and functional enrichment analysis. ResultsThe average litter size in the high-litter-size group (7.41±1.27) was significantly higher than that in the low-litter-size group (3.82±1.20) (P<0.05), and the total number of live offspring in the high-litter-size group (7.06±1.10) was extremely significantly higher than that in the low-litter-size group (3.67±1.11) (P<0.01). A total of 3 155 706 SNPs were detected in the two groups, 63.09% of which were located in intergenic regions, 33.96% in intronic regions, and 0.38%, 0.57%, and 0.09% in exonic regions, 3' untranslated regions (UTRs), and 5'UTRs, respectively. Among the SNPs in exonic regions, 5 256 were nonsynonymous variants, accounting for 43.55%. A total of 1 752 differential genes were identified after annotation screening. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified 13 candidate genes that may affect reproductive performance and litter size traits, including WDR35, SMAD7, RPGR, RERGL, PGRMC2, LOC482182, GIMD1, COX7B2, COX16, BMPR2, BMP6, BICD1, and SLC9C1. Their functions mainly involve reproductive hormone regulation, embryonic development, GTPase activation, and oocyte apoptosis. ConclusionEnglish Springer Spaniel breeding bitches have undergone significant artificial selection for litter size traits. These 13 candidate genes play key roles in oocyte maturation and regulation during early pregnancy, providing a new molecular basis for elucidating the genetic mechanism of canine reproductive traits.
6.Interpretation of perioperative immunotherapy for lung cancer in 2024 WCLC/ESMO
Jiahe LI ; Xiaopeng REN ; Jiayu LU ; Chenyuan ZHANG ; Ruitao FAN ; Xuxu ZHANG ; Xinyao XU ; Guizhen LI ; Jipeng ZHANG ; Wei LI ; Qiang LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):300-307
The 2024 World Conference on Lung Cancer (WCLC) and the European Society for Medical Oncology (ESMO) Annual Meeting, two of the most prestigious events in oncology, have concluded sequentially. As the most authoritative annual gatherings in lung cancer and the entire oncology field, the WCLC and ESMO conferences brought together top oncology experts and scientists from around the world to share, discuss, and publish the latest cutting-edge advancements in oncology. In both conferences, lung cancer immunotherapy remained a hot topic of considerable interest. This article aims to summarize and discuss the important research progress on perioperative immunotherapy for non-small cell lung cancer reported at the two conferences.
7.Clinical Efficacy of Tonifying Kidney and Replenishing Essence on Asthenospermia Patients with Syndrome of Kidney Essence Deficiency and Effect of This Method on Expression Levels of AMPK/mTORC1 Signaling Pathway-associated Proteins
Yuanjie FU ; Fuhao LI ; Chenghua PENG ; Dong XU ; Guoan YIN ; Xiaopeng HUANG ; Degui CHANG ; Liang DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):141-147
ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group, with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules, while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate (PR), total sperm motility (PR+NP), percentage of normal mitochondrial membrane potential (MMP), and traditional Chinese medicine (TCM) symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally, eight patients were randomly selected from the eligible patients in the observation group, and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK, phosphorylated (p)-AMPK, regulatory-associated protein of mTOR (RAPTOR) and p-RAPTOR, and PTEN-induced putative kinase 1 (PINK1) in sperms from the observation group before and after treatment, as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% (3/33), which was higher than that (3.33%, 1/30) in the control group. The total response rate was 84.8% (28/33) in the observation group and 66.7% (20/30) in the control group, with no statistically significant difference. After treatment, both groups were improved considering PR, PR+NP, MMP, and TCM symptom scores (P<0.01). Moreover, the observation group exhibited more pronounced decreases in TCM symptom scores than the control group (P<0.05), while the changes in PR, PR+NP, and MMP showed no statistical significance between groups. Compared with the control group, the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK (P<0.01). The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 (P<0.01). However, the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period, neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway, lowering the protein level of PINK1, and inhibiting excessive activation of mitophagy.
8.Clinical Efficacy of Tonifying Kidney and Replenishing Essence on Asthenospermia Patients with Syndrome of Kidney Essence Deficiency and Effect of This Method on Expression Levels of AMPK/mTORC1 Signaling Pathway-associated Proteins
Yuanjie FU ; Fuhao LI ; Chenghua PENG ; Dong XU ; Guoan YIN ; Xiaopeng HUANG ; Degui CHANG ; Liang DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):141-147
ObjectiveTo observe the clinical efficacy of tonifying kidney and replenishing essence on asthenozoospermia patients with the syndrome of kidney essence deficiency and the effects of this method on the adenosine 5′-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. MethodsSeventy-two eligible asthenozoospermia patients with the syndrome of kidney essence deficiency treated in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from February 2023 to January 2024 were selected and randomly assigned into an observation group and a control group, with 36 patients in each group. The observation group received oral administration of Guilu Tianjing capsules, while the control group received oral administration of L-carnitine oral solution. The treatment course lasted for 4 weeks in both groups. The observed indicators included sperm progressive motility rate (PR), total sperm motility (PR+NP), percentage of normal mitochondrial membrane potential (MMP), and traditional Chinese medicine (TCM) symptom scores before and after treatment in both groups. A three-month follow-up was instituted to record the conception status of the patients’ spouses. Additionally, eight patients were randomly selected from the eligible patients in the observation group, and four healthy males with normal semen routine examination results were included as the control group for the determination of protein expression. Western blotting was conducted to assess the expression of AMPK, phosphorylated (p)-AMPK, regulatory-associated protein of mTOR (RAPTOR) and p-RAPTOR, and PTEN-induced putative kinase 1 (PINK1) in sperms from the observation group before and after treatment, as well as in the sperms of the control group. ResultsThe pregnancy rate of spouses in the observation group was 9.09% (3/33), which was higher than that (3.33%, 1/30) in the control group. The total response rate was 84.8% (28/33) in the observation group and 66.7% (20/30) in the control group, with no statistically significant difference. After treatment, both groups were improved considering PR, PR+NP, MMP, and TCM symptom scores (P<0.01). Moreover, the observation group exhibited more pronounced decreases in TCM symptom scores than the control group (P<0.05), while the changes in PR, PR+NP, and MMP showed no statistical significance between groups. Compared with the control group, the asthenozoospermia group exhibited upregulations in phosphorylation levels of AMPK and RAPTOR and protein level of PINK (P<0.01). The administration of Guilu Tianjing Capsules led to downregulations in the phosphorylation levels of AMPK and RAPTOR and protein level of PINK1 (P<0.01). However, the protein levels of AMPK and RAPTOR demonstrated no significant difference between before and after treatment. During the study period, neither group of patients exhibited any notable adverse reactions. ConclusionGuilu Tianjing capsules can enhance the sperm motility and percentage of normal mitochondrial membrane potential in asthenozoospermia patients with the syndrome of kidney essence deficiency by downregulating the AMPK/mTORC1 signaling pathway, lowering the protein level of PINK1, and inhibiting excessive activation of mitophagy.
9.TiRobot-assisted minimally invasive treatment of geriatric fragility fractures of the pelvis.
Canhui LI ; Yonghong DAI ; Weiqiong CAI ; Xiaopeng SITU ; Yanhui ZENG ; Xuelian DU ; Shi HONG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(11):1421-1427
OBJECTIVE:
To investigate the effectiveness of TiRobot-assisted minimally invasive treatment for fragility fractures of the pelvis (FFP) in elderly patients.
METHODS:
A retrospective analysis was conducted on the clinical data of 176 patients with FFP who were admitted between July 2018 and July 2024 and met the selection criteria. Among them, 95 patients underwent TiRobot-assisted closed reduction and minimally invasive cannulated screw fixation (robot group), while 81 patients underwent traditional open reduction and plate screw fixation (control group). There was no significant difference in baseline data such as gender, age, fracture classification, disease duration, and preoperative visual analogue scale (VAS) pain scores between the two groups ( P>0.05). The following parameters were recorded and compared between the two groups, including operation time, intraoperative blood loss, intraoperative transfusion rate, volume of intraoperative blood transfusion, maximum incision length, hospital stay, maximum residual displacement, reduction quality, fracture healing time, incidence of complications, VAS scores, Majeed pelvic function scores, and functional grading.
RESULTS:
All surgeries in both groups successfully completed. The robot group exhibited significantly shorter operation time, reduced intraoperative blood loss, lower intraoperative transfusion rate, smaller volume of intraoperative blood transfusion, shorter maximum incision length, and shorter hospital stay compared to the control group ( P<0.05). In the robot group, a total of 14 INFIX internal fixation frames and 280 cannulated screws were implanted, among which 250 screws were rated as excellent, 17 as good, and 13 as poor, resulting in a screw placement excellent and good rate of 95.36%. Radiological review revealed that the excellent and good rate of reduction quality was in 91.58% (87/95) in the robot group and 81.48% (66/81) in the control group, with no significant difference in postoperative maximum residual fracture displacement or reduction quality between the two groups (P>0.05). All patients in both groups were followed up 12-66 months, with an average of 28.9 months, and there was no significant difference in follow-up time between the two groups ( P>0.05). The fracture healing time in the robot group was significantly shorter than that in the control group ( P<0.05). At last follow-up, both groups showed significant improvement in VAS scores compared to preoperative values ( P<0.05); the change values of VAS scores, Majeed scores, and the excellent and good rate of Majeed pelvic function were significantly higher in the robot group than in the control group ( P<0.05). Regarding postoperative complications, there was no significant difference between the two groups in terms of gait changes, secondary surgeries, heterotopic ossification, incision infections, walking difficulties, internal fixation failure, or mortality rates ( P>0.05); however, the incidence of delayed wound healing was significantly lower in the robot group than in the control group ( P<0.05).
CONCLUSION
TiRobot-assisted minimally invasive treatment of elderly FFP is superior to traditional open reduction and internal fixation in terms of surgical trauma control, postoperative rehabilitation speed, and functional recovery.
Humans
;
Male
;
Retrospective Studies
;
Female
;
Minimally Invasive Surgical Procedures/instrumentation*
;
Fracture Fixation, Internal/instrumentation*
;
Pelvic Bones/surgery*
;
Aged
;
Bone Screws
;
Bone Plates
;
Robotic Surgical Procedures/methods*
;
Aged, 80 and over
;
Treatment Outcome
;
Osteoporotic Fractures/surgery*
;
Operative Time
;
Blood Loss, Surgical
;
Fracture Healing
;
Fractures, Bone/surgery*
10.Engineered Escherichia coli Nissle 1917 targeted delivery of extracellular PD-L1-mFc fragment for treating inflammatory bowel disease.
Yuhong WANG ; Lin HU ; Lei WANG ; Chonghai ZHANG ; Wenhao SHEN ; Hongli YANG ; Min LI ; Xin ZHANG ; Mengmeng XU ; Muxing ZHANG ; Kai YANG ; Xiaopeng TIAN
Acta Pharmaceutica Sinica B 2025;15(11):6019-6033
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔpMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

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