ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

ObjectiveThis Study was conducted to investigate the interaction mechemisms between gutmicrobiota dysregulation and ischemic stroke by establishing a rat model of ischemic stroke and employing fecal microbiota transplantation (FMT). MethodsA preliminary experiment was conducted to establish an antibiotic-induced pseudo-sterile (ABX) rat model through antibiotic treatment, and a cerebral ischemia model was prepared using the middle cerebral artery occlusion (MCAO) method. Fecal microbiota from stroke patients and healthy individuals were transplanted via FMT, followed by behavioral testing. 16S rRNA sequencing was used to analyze the microbial community, hematoxylin and eosin (HE) staining to observe histopathological status, transmission electron microscopy (TEM) to examine the tight junction structure of the small intestine, and enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory factors and intestinal barrier-related markers. Results16S rRNA sequencing of fecal samples showed that compared with the normal control group and the metronidazole group, the abundance and diversity of fecal microorganisms in the quadruple antibiotic group were significantly reduced, indicating successful establishment of the ABX model. After transplanting fecal microbiota from stroke patients into ABX rats, significant changes in gut microbiota composition were observed. Behavioral tests revealed that the MCAO model group showed significant decreases in both horizontal movement and vertical exploration abilities. ELISA results indicated that IL-17 concentration in the ABX+mFMT (antibiotic-treated+model fecal microbiota transplantation) group was lower than in the ABX+cFMT (antibiotic-treated+control fecal microbiota transplantation) group, suggesting that IL-17 may serve as a key inflammatory indicator for evaluating the impact of stroke intervention on gut microbiota. Triphenyltetrazolium chloricle staining (TTC) staining suggested that gut microbiota intervention may increase the risk of stroke. HE staining showed that, except for the control group, all groups exhibited ischemic changes and inflammatory infiltration in brain tissues. TEM revealed that microvilli of small intestinal epithelial cells in the ABX+mFMT group were sparser than those in the ABX+cFMT group, indicating that microbial intervention affects intestinal barrier function. ConclusionThe ABX model established using broad-spectrum antibiotics showed no significant differences in physiological characteristics compared to normal rats, and the findings were consistent with those from germ-free rat models. Stroke prognosis appears to be influenced by intestinal dysbiosis, accompanied by significantly elevated levels of the pro-inflammatory cytokine IL-17, which may exacerbate neural injury via the gut-brain axis. Behavioral experiments indicated that transplantation of gut microbiota from stroke rats impaired cognitive function. Furthermore, IL-17 demonstrated sensitivity to alterations in the gut microbiota, suggesting its potential as a key therapeutic target for stroke intervention.

Wilson disease （WD） is an autosomal recessive disorder of copper metabolism， and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine （TCM） and points out that abnormal natural endowment is the core etiology and pathogenesis of WD， with internal accumulation of copper toxicity as the manifestation， liver/spleen/kidney dysfunction as the root cause， and intermingled “toxin， stasis， phlegm， and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD， including stagnation of liver Qi， internal retention of damp-heat， phlegm-stasis-heat accumulation syndrome， liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency， and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM， thereby giving full play to the advantages of TCM in the treatment of this disease.

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections. METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed. RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples. CONCLUSION Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.
Humans ; Blood Donors ; Hepatitis B/blood* ; China/epidemiology* ; Adult ; Male ; Female ; Hepatitis D/epidemiology* ; Middle Aged ; Hepatitis B virus/immunology* ; Hepatitis B Antibodies/blood* ; Young Adult ; DNA, Viral/blood* ; Hepatitis B Surface Antigens/blood* ; Prevalence ; Adolescent

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr⁺ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat⁺Oxtr⁺ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals ; Receptors, Oxytocin/metabolism* ; Male ; Brain/growth & development* ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism* ; Single-Cell Analysis ; Gene Expression Regulation, Developmental ; RNA, Messenger/metabolism* ; Animals, Newborn

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*