Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess， and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 （STAT3）/vascular endothelial growth factor （VEGF） signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine， 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method， with 30 cases in each group. The control group received conventional treatment， while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7^th， 14^th and 21^st day after operation， enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. Hematoxylin eosin （HE） staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 （p-STAT3） and vascular endothelial growth factor （VEGF） proteins， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain， secretion volume score， and healing rate of patients on the 3^rd， 7^th， 14^th， and 21^st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group （P<0.05）. For intra-group comparison， the pain score of the control group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The secretion volume score decreased on the 14^th and 21^st days after operation （P<0.05）. The pain score and secretion volume score of the treatment group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The levels of various inflammatory factors decreased in both groups （P<0.05）. Compared with those on the surgical day， the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7^th and 21^st days after operation （P<0.05）. There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period （P<0.01）. For inter-group comparison， on the 7^th and 14^th days after operation， the pain score in the treatment group was lower than that in the control group. On the 7^th， 14^th and 21^st days after operation， the secretion volume scores and healing rate of the treatment group were better than those of the control group （P<0.05）. The levels of various inflammatory factors in the treatment group were lower than those in the control group （P<0.05）， and the decline rate was faster （P<0.05）. On the 7^th day after operation， the levels of p-STAT3， VEGF protein， and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group （P<0.05）. HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly， and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery， reduce secretions， and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β， IL-6， and TNF-α， reducing the inflammatory response of the wound， upregulating the expression of p-STAT3 and VEGF proteins， and stimulating the STAT3/VEGF signaling pathway， thereby accelerating angiogenesis and promoting wound healing.

The patient was a 56-year-old man who presented with abnormal urinalysis findings of over one month’s duration. Serological tests revealed an elevated serum free light chain κ/λ ratio, and immunofixation electrophoresis detected an IgG-κ monoclonal band. Renal biopsy demonstrated membranous nephropathy, with electron-dense deposits observed in the subepithelial space and mesangium on electron microscopy. Immunofluorescence confirmed glomerular deposits of IgG_1/IgG₃-κ. Based on clinical manifestation, bone marrow flow cytology, and lymph node pathology, the patient was diagnosed with small lymphocytic lymphoma (SLL), and membranous nephropathy with light chain-restricted deposition (IgG₁/IgG₃-κ) secondary to SLL. After receiving obinutuzumab treatment, the patient’s proteinuria partially remitted, the lymph nodes significantly shrank, and clinical remission was achieved.

Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.

Objective To explore the predictive value of artificial intelligence (AI)-based lung nodule CT quantitative analysis for the invasion degree of lung adenocarcinoma spectrum lesions. Methods According to the invasion degree of lung adenocarcinoma spectrum lesions, patients with surgically and pathologically confirmed lung adenocarcinoma spectrum lesions from January to June 2023 in Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University were retrospectively collected and divided into a non-invasive group and an invasive group, including atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma patients in the non-invasive group, and invasive adenocarcinoma patients in the invasive group. All enrolled patients underwent chest CT before surgery, and then the lung nodules were quantitatively analyzed using an AI-based computer-aided diagnosis system to compare the related quantitative parameters of lung nodules that have been surgically removed and pathologically confirmed as lung adenocarcinoma spectrum lesions between the two groups. The relationship between various CT quantitative features and the invasion degree of lung adenocarcinoma spectrum lesions was analyzed. Results A total of 149 patients (149 lesions) were included, including 42 males and 107 females, aged 29-81 (56.35±10.75) years. There were 72 patients in the non-invasive group and 77 patients in the invasive group. Statistical differences were observed between the two groups in long diameter, short diameter, volume, surface area, mass, maximum cross-sectional area, 3D long diameter, maximum CT value, minimum CT value, average CT value, entropy, kurtosis, skewness, malignancy probability and other indicators (P<0.05). Multivariate binary logistic regression analysis showed that long diameter [OR=1.687, 95%CI (1.364, 2.085), P<0.001], average CT value [OR=1.006, 95%CI (1.002, 1.009), P=0.002], and malignancy probability [OR=1.034, 95%CI (1.005, 1.063), P=0.020] were independent risk factors for the invasion degree of lung adenocarcinoma. The predictive model combining the above parameters demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.951, sensitivity of 0.818, and specificity of 0.972. Using a Nomogram to quantify the three independent risk factors, the cross-validation was performed to evaluate the stability of the model, and the average C-index of cross-validation was 0.950, with each fold C-index >0.75, indicating that the prediction performance of the model was stable, and the calibration curve and decision curve indicated good predictive performance. Conclusion The visualization prediction model constructed by AI-based quantitative analysis of lung nodules in CT demonstrates significant discriminative effectiveness in the assessment of invasiveness in lung adenocarcinoma spectrum lesions. This visualization prediction model can provide a quantitative decision-making basis for the preoperative identification of the degree of invasiveness in lung adenocarcinoma spectrum lesions.

Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

To develop a novel immunocastration vaccine for animals,researchers designed and syn-thesized the recombinant plasmid pET-30a-SF which could express the recombinant protein SF.This protein was then conjugated in vitro with the synthetic peptide STGP to prepare the SF-STGP nanoparticle vaccine,and its immunocastration effect on mice was studied.The Spy Catcher and ferritin amino acid sequences were connected via GGGGS,and after codon optimization for E.coli,the recombinant plasmid pET-30a-SF was constructed and transformed into E.coli for in-duced expression.The recombinant protein SF was purified using Ni-column affinity chromatogra-phy and characterized.The peptide STGP,composed of Spy Tag,GnRH,and PADRE connected by GGGS,was conjugated with the recombinant protein SF in vitro.The self-assembled nanoparticles were observed using transmission electron microscopy(TEM)and dynamic light scattering(DLS).The prepared SF-STGP nanoparticles were mixed with MONTANIDE ISA 206 VG at a 1∶1 ratio to form the vaccine,which was then subcutaneously injected into male BALB/c mice for immunocastration evaluation.The recombinant protein SF showed the highest soluble expression when induced at 18 ℃ with 0.25 mmol/L IPTG for 14 h,and the maximum conjugation efficiency with STGP was achieved at a 1∶8 molar ratio.TEM and DLS analyses revealed that both the re-combinant protein SF and SF-STGP could self-assemble into nanoparticles with average diameters of 16.2 nm and 17.8 nm,respectively.Mouse immunization results demonstrated that the SF-STGP nanoparticle vaccine generated specific GnRH antibodies after the first immunization,with the spe-cific antibody D45o reaching its peak at the 10 th week.The SF-STGP+ISA 206 immunization group showed a peak D450 value of 2.8,and the specific antibody levels in all immunization groups were significantly higher than those in the control group(P＜0.05).Additionally,the SF-STGP nanoparticle vaccine effectively reduced serum testosterone levels in mice,with the testosterone concentration in the immunization groups being significantly lower than that in the control group(P＜0.05).Compared to the control group,the immunization group exhibits testicular atrophy.The constructed SF-STGP nanoparticle vaccine proves to be a highly effective immunogen,capable of inducing testicular atrophy and reducing gonadal hormone concentrations,demonstrating excellent castration effects.This study provides new insights into immunocastration vaccines for mammals.

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with thunder-fire moxibustion in treating low back pain with cold-damp. METHODS: Seventy-two patients of low back pain with cold-damp were randomly divided into an observation group (36 cases, 1 case was eliminated) and a control group (36 cases, 1 case dropped out). The control group received acupuncture at Jizhong (GV6), Yaoyangguan (GV3), ashi points, bilateral Shenshu (BL23), Dachangshu (BL25), and Weizhong (BL40) for 30 min daily. The observation group was treated with thunder-fire moxibustion in addition to the same acupuncture regimen as the control group, once daily. Both groups were treated for 6 consecutive days followed by one rest day, for a total duration of 4 weeks. The visual analog scale (VAS) score, Oswestry disability index (ODI) score, Japanese Orthopedic Association (JOA) score, present pain intensity (PPI) score, and serum levels of β-endorphin (β-EP), 5-hydroxytryp tamin (5-HT), and substance P (SP) were compared before and after treatment, and the clinical efficacy was also compared between the two groups. RESULTS: Compared before treatment, the VAS scores, ODI scores, PPI scores, and serum levels of 5-HT and SP were decreased (P<0.01), while JOA scores and serum levels of β-EP were increased (P<0.01) in both groups after treatment. The observation group showed lower VAS, ODI, and PPI scores and serum levels of 5-HT and SP than those in the control group (P<0.05), as well as higher JOA score and serum level of β-EP (P<0.05). The total effective rate in the observation group was 94.3% (33/35), higher than 82.9% (29/35) in the control group (P<0.05). CONCLUSION Acupuncture combined with thunder-fire moxibustion could effectively alleviate pain and improve lumbar function in patients of low back pain with cold-damp, possibly by regulating β-EP, 5-HT, and SP levels.
Humans ; Moxibustion ; Low Back Pain/blood* ; Male ; Female ; Adult ; Middle Aged ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Combined Modality Therapy ; beta-Endorphin/blood* ; Young Adult ; Aged