1.Mechanism of Guihuang Formula in Regulating NLRP3 Inflammasome-mediated Pyroptosis in Treatment of Chronic Prostatitis
Qinghe GAO ; Jianhua FU ; Shengjing LIU ; Ziwei ZHAO ; Ming ZHAO ; Boda GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):108-116
ObjectiveTo observe the mechanism of Guihuang formula in regulating the activation of NOD-like receptor protein 3 (NLRP3) inflammasome and inhibiting pyroptosis in the treatment of type Ⅲ prostatitis. Methods(1) In an animal experiment, 50 Sprague Dawley (SD) rats were randomly divided into a blank group, a model group, and low-dose, medium-dose, and high-dose groups of Guihuang formula, with 10 rats in each group. Except for the blank group, the type Ⅲ prostatitis rat model was prepared for the other four groups.After the modeling was successful, the blank group and the model group were given normal saline intragastrically, and the low-dose, medium-dose, and high-dose groups of Guihuang formula were given intragastrically with Guihuang formula (4.9, 9.8, 19.6 g·kg-1). After 30 days of intragastrical administration, samples were taken for detection. Inflammatory cell infiltration in prostate tissue was observed by hematoxylin-eosin (HE) staining, and serum IL-1β and IL-18 levels were measured by enzyme-linked immunosorbent assay (ELISA). Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined by biochemistry. NLRP3 expression in prostate tissue was assessed by immunohistochemistry, and the expression of NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), and gasdermin D (GSDMD) in prostate tissue was measured by Western blot. (2) In a cell experiment, human normal prostate epithelial cells (RWPE-1 cells) were divided into a blank group, a model group, a Guihuang formula group, and an NLRP3 inhibitor group (MCC950 group). Except for the blank group, the other three groups were stimulated by 100 μg·L-1 lipopolysaccharide (LPS) for 4 h and 5 mol·L-1 adenosine triphosphate (ATP) for 30 min to prepare the pyroptosis model. After successful modeling, blank serum was given to the blank group and the model group. 6.25 μg·mL-1 Guihuang formula drug-containing serum was added to the Guihuang formula group, and MCC950 was added to the MCC950 group on the basis of the model group. Propidium iodide (PI) uptake and Caspase-1 expression were detected by flow cytometry, and lactate dehydrogenase (LDH) level in the cell supernatant was measured by biochemistry. Interleukin (IL)-1β and IL-18 levels of the cell supernatant were determined by ELISA, and the expression of NLRP3, Caspase-1, and GSDMD was detected in Western blot. Results(1) For the animal experiment, compared with the blank group, the model group showed significant infiltration of inflammatory cells in prostate tissue, while the low-dose, medium-dose, and high-dose groups of Guihuang formula showed reduced infiltration of acinar inflammatory cells, reduced degree of glandular epithelial degeneration and interstitial edema, and significantly reduced degree of damage. Compared with those in the blank group, the levels of IL-1β and IL-18 in the serum of the model group were significantly increased (P<0.01). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significant decrease in serum IL-1β and IL-18 levels (P<0.01). Compared with that in the blank group, the serum MDA level in the model group significantly increased (P<0.01). Compared with that in the model group, the MDA level in the low-dose, medium-dose, and high-dose groups of Guihuang formula was significantly reduced (P<0.01). Compared with those in the blank group, the levels of SOD and GSH-Px in the serum of the model group significantly decreased (P<0.05). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significantly increase in SOD (P<0.01). Compared with the model group, the low-dose, medium-dose, and high-dose groups of Guihuang formula showed a significantly increase in GSH-Px (P<0.05). Immunohistochemistry showed that compared with the blank group, the model group had high expression of NLRP3 molecule in prostate tissue. The expression of NLRP3 in the low-dose, medium-dose, and high-dose groups of Guihuang formula was significantly lower than that in the model group. Compared with those in the blank group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins in the prostate tissue of the model group were significantly increased (P<0.01). Compared with those in the model group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins in the low-dose, medium-dose, and high-dose groups of Guihuang formula were significantly inhibited (P<0.01). (2) For the cell experiment, compared with that in the blank group, the PI uptake rate of RWPE-1 cells in the model group significantly increased (P<0.01). Compared with that in the model group, the PI uptake rate of the Guihuang formula group and the inhibitor group significantly decreased (P<0.01). Compared with that in the blank group, the expression of Caspase-1 in the model group was significantly higher (P<0.01). Compared with that in the model group, the Caspase-1 in the Guihuang formula group and the inhibitor group significantly decreased (P<0.01). Compared with the blank group, the model group showed an increase in LDH release (P<0.01). Compared with the model group, the Guihuang formula group and the inhibitor group showed a significantly decrease in LDH release (P<0.01). Compared with those in the blank group, the levels of IL-1β and IL-18 in the supernatant of the model group were significantly increased (P<0.01). Compared with the model group, the Guihuang formula group and the inhibitor group showed a significantly decrease in the levels of IL-1β and IL-18 (P<0.01). Compared with those in the blank group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins significantly increased in the model group (P<0.01). Compared with those in the model group, the protein expression levels of NLRP3, Caspase-1, and GSDMD were significantly reduced in the Guihuang formula group and inhibitor group (P<0.01). ConclusionGuihuang formula can inhibit the activation of Caspase-1, prevent GSDMD cleavation and lysis, and inhibit cell pyrodeath in the treatment of type Ⅲ prostatitis by inhibiting the activation of NLRP3 inflammasome.
2.Adra2a Regulates LPS-Induced Inflammation in Hepatocytes of Lbp-/- Mice via the MAPK Signaling Pathway
Sai LIU ; Bin FU ; Sidi LI ; Zhida CHEN ; Yue ZHANG ; Zhongkun GUO ; Yongan WANG ; Kezhou WANG
Laboratory Animal and Comparative Medicine 2026;46(2):212-221
ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp-/- mice through the MAPK signaling pathway.
3.Expert Consensus on Neurocritical Care Monitoring and Management in Beijing and Tibet(2025)
Drolma PHURBU ; Wenjin CHEN ; Heng ZHANG ; Jian ZHANG ; Xiaomeng WANG ; Guoying LIN ; Wenjun PAN ; Xiying GUI ; Xin CAI ; Chodron TENZIN ; Jianlei FU ; Qianwei LI ; TSEYANG ; Yijun LIU ; Bo LIU ; Tsering DROLMA ; Yudron SONAM ; KYILV ; Samdrup TSERING ; Wa DA ; Juan GUO ; Cheng QIU ; Huan CHEN ; Xiaoting WANG ; Yangong CHAO ; Dawei LIU ; Wenzhao CHAI ; Chenggong HU ; Wanhong YIN ; Shihong ZHU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):59-72
Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.
4.Overview of Physical Biological Research on the Activation of Acupoint Effects by Acupuncture
Junyi LI ; Shiwei TU ; Yangyang LIU ; Baomin DOU ; Zezhi FAN ; Jiangjiang FU ; Jiangqi ZHOU ; Kaiyuan DENG ; Yanwei LI ; Yi GUO
Journal of Traditional Chinese Medicine 2026;67(10):1130-1136
By reviewing the physical biological research on the activation of acupoint effects by acupuncture, this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture, and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells, further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints, and the physical-chemical information transduction mechanism, which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.
5.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
6.Comparison of decompression effects between spine endoscopy hybrid technique and uniportal endoscopic surgery in treatment of lumbar spinal stenosis with bilateral symptom
Song GUO ; Xinhua LI ; Meijun YAN ; Yanbin LIU ; Zhong LIU ; Kewei LI ; Pengcheng LIU ; Beiting ZHANG ; Qiang FU
Chinese Journal of Tissue Engineering Research 2025;29(3):517-523
BACKGROUND:Spinal canal decompression using uniportal endoscopic surgery is a new minimally invasive surgery in the treatment of lumbar spinal stenosis.However,this technique needs a steep learning curve and high requirements for surgical equipment and instruments,which limits its clinical application.We previously use the spinal endoscopy as a monitoring endoscopy and combined with unilateral biportal endoscopy to propose a hybrid technique of spinal endoscopy to achieve coaxial endoscopic operation and hands-separate operation. OBJECTIVE:To compare the clinical outcome of hybrid technique and uniportal endoscopic surgery in treatment of lumbar spinal stenosis with bilateral lower limb pain symptoms. METHODS:Ninety patients diagnosed of lumbar spinal stenosis with bilateral symptoms were included and retrospectively analyzed at First People's Hospital,Shanghai Jiao Tong University from August 2020 to August 2022.44 cases were included in group A(hybrid technique group),while 46 cases were included in group B(uniportal endoscopic surgery).The nerve decompression was observed during the surgery.Operation time,hospital stay time,and expenses were recorded in both groups.The visual analog scale scores of lower back pain and both lower extremities pain,Oswestry disability index scores of quality of life and excellent and good rate of modified Macnab criteria were recorded and compared at preoperative,postoperative 3 days,and postoperative 3 and 6 months. RESULTS AND CONCLUSION:(1)The operation time of group A was significantly shorter than that of group B(P<0.05).(2)The lower back pain and lower extremity pain of the severe side at postoperative 3 days,and 3 and 6 months were significantly relieved in both groups(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days,3 and 6 months than preoperative score in the group A(P<0.05).The visual analog scale score of lower extremity pain on the mild side was significantly decreased at postoperative 3 days than preoperative score in the group B(P<0.05).The visual analog scale scores of lower extremity pain on the mild side at postoperative 3 and 6 months did not show significant difference than preoperative score in the group B.The comparison between the two groups showed that there was no significant difference in the visual analog scale scores of postoperative lower back pain and lower extremity pain of the severe side(P>0.05).The visual analog scale scores of lower extremity pain on the mild side in the group A were significantly lower than those of group B at postoperative 3 and 6 months(P<0.05).(3)The Oswestry disability index scores of both groups at postoperative 3 day were significantly lower than preoperative score(P<0.05),and there was no significant difference between the two groups 3 days after operation.Oswestry disability index scores of group A at postoperative 3 and 6 months were significantly decreased than preoperative score(P<0.05).The Oswestry disability index scores of group B at postoperative 3 and 6 months did not show significant differences than preoperative score(P>0.05).The comparison between the two groups showed the Oswestry disability index scores of group A were significantly lower than group B at postoperative 3 and 6 months(P<0.05).(4)The results of modified Macnab showed that the excellent and good rate of group A was significantly higher than that of group B(95%,78%,P<0.05).(5)It is indicated that the hybrid technique is a new spinal endoscopy technique,which has the advantages of less trauma and faster recovery as a minimally invasive surgery.The clinical outcome of hybrid technique is superior to that of uniportal endoscopic surgery in the treatment of lumbar spinal stenosis with bilateral symptoms.Additionally,it also has the advantages of good operational flexibility and high decompression efficiency as an open surgery.
7.Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis.
Ruo-Fan XI ; Xin LIU ; Yi WANG ; Han-Zhi LU ; Shao-Jie YUAN ; Dong-Jie GUO ; Jian-Yong ZHU ; Fu-Lun LI ; Yan-Juan DUAN
Journal of Integrative Medicine 2025;23(6):721-732
OBJECTIVE:
Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism.
METHODS:
Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway.
RESULTS:
Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin.
CONCLUSION
Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals
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Psoriasis/chemically induced*
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Mice
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AMP-Activated Protein Kinases/metabolism*
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Disease Models, Animal
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Cupping Therapy/methods*
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Signal Transduction
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Imiquimod
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Ion Channels/genetics*
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Male
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Mechanotransduction, Cellular
8.High-risk factors for significant liver histopathological damage in patients with indeterminate phase of chronic HBV infection
Wenchang WANG ; Xuyang LI ; Chunyan WANG ; Mengwen HE ; Yifan GUO ; Yiming FU ; Miao LIU ; Dong JI
Journal of Clinical Hepatology 2025;41(11):2258-2264
ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection, as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022, among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment (2022 edition) were enrolled, and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system, with stages 0 — 4 for inflammation grade (G) and stages 0 — 4 for fibrosis degree (S), and the patients were divided into groups based on the presence of significant necroinflammation (≥G2) and significant liver fibrosis (≥S2). The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors, and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled, among whom 61 (22.5%) had significant necroinflammation (≥G2) and 124 (45.8%) had significant liver fibrosis (≥S2). The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L (for male patients) or ≥19 U/L (for female patients) (odds ratio [OR]=2.69, 95% confidence interval [CI]: 1.39 — 5.21, P=0.003), HBV DNA ≥2 000 IU/mL (OR=2.75, 95%CI: 1.38 — 5.48, P=0.004), and liver stiffness measurement (LSM) ≥6.0 kPa (OR=4.57, 95%CI: 2.17 — 9.62, P<0.001) were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL (OR=1.82, 95%CI: 1.01 — 3.32, P=0.049) and LSM ≥6.0 kPa (OR=2.06, 95%CI: 1.23 — 3.43, P=0.006) were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection, a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.
9.Protective effect of adipose-derived stem cells combined with acellular scaffolds on dorsal root ganglion in rats with sciatic nerve injury and its mechanism
Xiaomin YU ; Qinghua ZHU ; Yilun WANG ; Miao REN ; Zijia LIU ; Yongyi YU ; Yuanliang DU ; Donghui LIU ; Sen GUO ; Xiumei FU
Journal of Jilin University(Medicine Edition) 2025;51(6):1542-1550
Objective:To observe the effects of adipose-derived stem cells(ADSC)combined with acellular scaffold(AS)on the ultrastructure of dorsal root ganglion and the protein and mRNA expression levels of ciliary neurotrophic factor(CNTF),Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phosphorylated STAT3(p-STAT3)in the rats with sciatic nerve injury(SNI),and to clarify the protective effect of ADSC combined with AS on dorsal root ganglion in the SNI rats and its possible mechanism.Methods:The rat ADSCs were isolated and cultured and their multidirectional differentiation potential was detected.The AS of rats was prepared,and ADSCs were injected into the AS to construct tissue-engineered nerve.A total of 36 rats were randomly divided into control group,model group,AS group,and ADSC+AS group.The rats in control group were routinely fed,and the rats in other groups were used to establish the SNI models by resecting 10 mm of right sciatic nerve.The rats in model group received no further treatment,while the rats in AS group and ADSC+AS group were bridged with AS and the constructed tissue-engineered nerve at the two ends of the injured nerve,respectively.At 6 weeks after surgery,transmission electron microscope was used to observe the ultrastructure of dorsal root ganglion of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of CNTF,p-JAK2,and p-STAT3 in dorsal root ganglion of the rats;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of CNTF,JAK2,and STAT3 in dorsal root ganglion of the rats in various groups.Results:After 7 d of primary ADSC culture,a large number of large and long spindle-shaped cells were observed under the inverted microscope,arranged in clusters or whirlpools;red lipid droplets were observed with oil red O staining under microscope,and calcified nodules were observed with Alizarin red staining under microscope,indicating that the isolated and cultured cells had multidirectional differentiation ability.Compared with normal nerve tissue,the level of DNA in AS of rats was significantly decreased(P<0.05).Compared with control group,the nuclear membrane of dorsal root ganglion cells in model group was uneven and serrated,the number of organelles in the cytoplasm was decreased,mitochondria were swollen with broken or missing cristae and unclear structure;the CNTF protein and mRNA expression levels were significantly decreased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly increased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly increased(P<0.01).Compared with model group,the serrated change of nuclear membrane of the dorsal root ganglion cells in AS group was significantly alleviated,the number of organelles in the cytoplasm was increased,and mitochondrial swelling was reduced;in ADSC+AS group,the nuclear membrane of dorsal root ganglion cells tended to be intact,the number of organelles was increased,and mitochondrial swelling and vacuolization were significantly reduced;the CNTF protein and mRNA expression levels in the dorsal root ganglion in AS group and ADSC+AS group were significantly increased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Compared with AS group,the CNTF protein and mRNA expression levels in ADSC+AS group were significantly increased(P<0.05 or P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Conclusion:The application of ADSC combined with AS can improve the ultrastructure of dorsal root ganglion in the SNI rats,and the mechanism may be related to the increased CNTF expression and decreased activation of the JAK2/STAT3 signaling pathway in the dorsal root ganglion by ADSC combined with AS application.
10.Clinical characteristics and contributors to diagnostic delay in autoimmune gastritis
Haofeng LI ; He MA ; Tao FU ; Xinyi HUANG ; Qing SHI ; Yan ZHENG ; Hanning LIU ; Hengqi LIU ; Yan GUO ; Chunhui LAN
Journal of Army Medical University 2025;47(19):2396-2404
Objective To analyze the diagnostic process and clinical characteristics of autoimmune gastritis(AIG)in order to improve the awareness and diagnostic proficiency of this disease.Methods A retrospective cohort study was conducted on 114 patients diagnosed with AIG in Army Medical Center of PLA between January 2021 and June 2024.Comprehensive statistical analysis was performed on clinical data,including demographic characteristics(age,sex),clinical symptoms,comorbidities,diagnostic process,Helicobacter pylori(H.pylori)infection and treatment history,laboratory indicators[results of routine blood test,anemia-related indices,thyroid function,anti-parietal cell antibody(APCA),intrinsic factor antibody(IFA)],and gastrointestinal endoscopic findings(frequency and endoscopic features).Results Among the 114 patients,males accounted for 28.1%(32/114)and females for 71.9%(82/114),and they were at a mean age of 56.3±8.4 years.Predominant symptoms included epigastric/upper abdominal pain(47.4%,54/114)and postprandial fullness(43.0%,49/114),while 24.6%(28/114)reported acid reflux or heartburn.Diagnostic delay occurred in 76.4%(87/114)of patients,with a median delay duration of 11.5 months.Primary diagnostic clues were endoscopic reverse gradient atrophy(significantly more severe mucosal atrophy in the gastric corpus/fundus versus antrum;53.5%,61/114)and repeated H.pylori eradication failure(≥2 attempts;22.8%,26/114).Positivity rate of thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TgAb)was 56.9%(33/58)and 36.2%(21/58),respectively.APCA positive rate was 98.8%(81/82),IFA positive rate was 34.1%(28/82),and dual-antibody rate was 32.9%(27/82).Anemia was present in 25.7%(26/101)of the patients.Gastric neuroendocrine tumors(NET)were found in 12.2%(14/114),intraepithelial neoplasia in 5.3%(6/114),and gastric adenocarcinoma in 0.9%(1/114).Among colonoscopy-examined patients,tubular adenomas occurred in 25.0%(13/52)and colorectal malignancies in 3.4%(2/58).There were 18.4%(21/114)patients having gallbladder-related diseases,7.9%(9/114)having diabetes mellitus,and 1.8%(2/114)of subacute combined degeneration of the spinal cord.Conclusion AIG is frequently associated with diagnostic delay.The reverse pattern of atrophy on endoscopy serves as a critical diagnostic clue,necessitating enhanced recognition in endoscopists.Patients with recurrent H.pylori eradication failure(≥2 attempts)should be evaluated for AIG.


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