BACKGROUND: Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing. METHODS: An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance. RESULTS: KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA. CONCLUSION KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals ; Osteoarthritis/metabolism* ; Signal Transduction/drug effects* ; Rats ; Rats, Sprague-Dawley ; Humans ; Male ; Hypoxia-Inducible Factor 1/metabolism* ; Interleukin-1beta

Yttrium-90(90Y)selective internal radiation therapy(SIRT)is an emerging modality for the treatment of hepatocellular carcinoma(HCC),leveraging the nuclide 90Y to deliver targeted radiation therapy.90Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays.It has high biological effectiveness and robust local control capabilities.In recent years,with the continuous advancement of basic and clinical research,the application of 90Y-SIRT in the conversion treatment of unresectable HCC(uHCC)has made significant progress.However,challenges remain in the clinical application of 90Y-SIRT,including how to improve the efficacy of conversion therapy and how to optimize therapy regimens.This review aims to summarize the research progress of90Y-SIRT in the conversion therapy of uHCC.

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective:To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) .Methods:This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate.Results:(1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions:Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Derived from embryonic stem cells, induced pluripotent stem cells, or adult stem cells, liver organoids not only mimic the tissue structure, gene expression patterns, and genetic characteristics of in vivo liver but also demonstrate significant potential in simulating liver diseases, drug screening, precision medicine, and regenerative medicine. This technology is particularly valuable in modeling various conditions such as malignant liver tumors, liver fibrosis, cirrhosis, viral hepatitis, and a range of genetic and metabolic liver diseases. However, challenges remain in enhancing the derivation and proliferation efficiency of organoids, constructing immune microenvironments, developing functional vascular networks, and achieving standardization and automation in the organoid preparation process. Looking forward, with continued technological advancements and innovations, these issues are expected to be resolved, paving the way for liver organoids to play a more substantial role in clinical and research applications, ultimately contributing significantly to public health. This review comprehensively explores the development and extensive applications of liver organoid technology in the field of biomedical science. The aim is to inform subsequent research.

Objective:To analyze the relationship between allergen reactivity, atopic disease history and clinical features in patients with chronic inducible urticaria (CIndU) .Methods:A retrospective analysis was conducted on clinical data and follow-up results from 168 patients with CIndU in the Department of Dermatology, Southwest Hospital of Army Medical University from June 2014 to June 2015. Associations were analyzed between allergen reactivity, atopic disease history and clinical characteristics (including patient global assessment [PGA] scores, pruritus intensity, dermatology life quality index [DLQI], proportions of cases with complicated angioedema, natural course, etc.) in patients with different CIndU subtypes. Chi-square test, Mann-Whitney U test and Kaplan-Meier survival analysis were used for statistical analysis. Results:Among the 168 patients with CIndU, 117 were diagnosed with symptomatic dermographism (SD) , 32 with cold contact urticaria (CCU) , 5 with heat contact urticaria (HCU) , and 14 with cholinergic urticaria (CholU) ; there were 46 (39.3%) , 14 (43.8%) , 3, and 9 patients with positive skin prick test (SPT) among the patients with SD, CCU, HCU and CholU respectively, and no significant difference was observed in the positive rate of SPT among patients with different CIndU subtypes ( χ2 = 3.86, P = 0.283) . The SPT-positive CIndU patients showed significantly increased PGA scores, pruritus scores, DLQI scores and proportions of cases with complicated angioedema compared with the SPT-negative patients (all P<0.05) ; the CIndU patients with a personal or family history of atopic diseases also showed significantly increased PGA and DLQI scores compared with those without (both P < 0.05) . For different CIndU subtypes, the pruritus scores, PGA scores, DLQI scores, and proportions of cases with complicated angioedema were significantly higher in the SPT-positive SD patients than in the SPT-negative SD patients (all P < 0.05) ; the DLQI scores were significantly higher in the SPT-positive CholU patients than in the SPT-negative CholU patients ( Z = -2.28, P = 0.019) ; the pruritus scores were significantly higher in the CCU patients with a personal or family history of atopic diseases than in those without ( Z =-2.41, P = 0.022) . Conclusion:The allergen reactivity and atopic disease history of CIndU patients were associated with disease severity, pruritus intensity, quality of life, and the proportion of cases with complicated angioedema, but their relationship with the natural course of CIndU needs to be confirmed by further studies.

Objective : To explore the prognostic value of chemoradiotherapy based on the depth of invasion (DOI) in patients with oral squamous cell carcinoma. Methods : Patients with oral squamous cell carcinoma who received surgical treatment in a hospital from 2008 to 2016 were enrolled. The chi-square test was used to compare the effects of DOI on postoperative cervical lymph node metastasis and local recurrence. The effects of chemoradiotherapy on postoperative cervical lymph node metastasis, local recurrence, and survival were analyzed based on the DOI. Results: A total of 111 patients with oral squamous cell carcinoma were included in this study. The postoperative local recurrence rate (P<0.05) and cervical lymph node metastasis rate (P<0.05) of patients with 5 mm < DOI ≤ 10 mm and DOI > 10 mm were significantly higher than those with DOI ≤ 5 mm. The time of postoperative recurrence was concentrated within two years after the operation. The greater the DOI was, the shorter the time to postoperative recurrence (P<0.05). The addition of postoperative chemoradiotherapy did not significantly improve the postoperative local recurrence rate, cervical lymph node metastasis or survival rate of patients with different DOIs (P > 0.05). Conclusion DOI has important predictive value for postoperative recurrence, cervical lymph node metastasis and survival rate. However, DOI cannot be used as an independent index to guide whether chemoradiotherapy is needed after oral cancer surgery.

Objective:To introduce a surgical method and clinical effect of using Masquelet technique combined with skin graft to cover chronic refractory wounds in elderly patients.Methods:From September 2020 to September 2022, 20 elderly patients with wounds of bone or tendon exposure in lower limbs were treated in the Department of Wound Repair, the Second Affiliated Hospital of Wenzhou Medical University. Due to the age and poor general condition of the patients, flap transfer for wound coverage were not allowed. Masquelet technique was therefore applied in the treatment of chronic wounds of such patients. Sizes of wounds were found at 4.5 cm×3.0 cm to 15.0 cm×6.0 cm and all accompanied with tendon and bone exposure, after thorough debridement. Wounds were then sealed with antibiotic bone cement several times. After having induced formation of membrane in wounds, free mesh skin graft was used to cover the refractory wounds. The patients were entered in follow up regularly after surgery at outpatient service, and telephone or video reviews. The wound healing of patients and whether there were related complications in the skin donor area were observed. The number of operation times in the first stage was 1-4 with an average of 1.3 times ± 0.7 times. Lower Extremity Function Scale (LEFS) was used to evaluate the recovery of lower limb function.Results:All 20 wounds healed well. The follow-up time was 3-12 months, with an average of 7.6 months. The appearance and texture of the skin in the wounds area were satisfactory. The mean LEFS was 69.83 point ± 10.82 point.Conclusion:Using Masquelet technique combined with free skin grafting to treat refractory wounds in the elderly patients can achieve satisfactory clinical outcomes. It is a simple and reliable supplement to the wound repair, and can reduce the surgical risk.

Objective:To investigate the clinical effects of expanded frontal flap and flip scar flap in repairing partial nasal defect.Methods:A retrospective observational study was conducted. From January 2012 to January 2022, 26 patients with partial nasal defects who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 19 males and 7 females, aged 5 to 61 years. The surgery was performed in 4 stages. In the first stage, a rectangular skin and soft tissue expander (hereinafter referred to as expander) with suitable rated capacity was planted in frontal region and expanded by injecting water regularly. In the second stage, flip scar flap was grafted to reconstruct nasal inner lining, whose area was about 10% larger than the area of defect. The expanded frontal flap with pedicle was transferred to repair the nasal defect, whose pedicle was supraorbital vessel or supratrochlear vessel on the contralateral side of the defect, and the area of expanded flap was 20% larger than the nasal defect area after resection and flipping of scar flap. The donor site of expanded flap was sutured directly. After 3 weeks of flap transferring, the flap was delayed in the third stage. After 1 week of delaying operation, the pedicle of flap was cut off in the fourth stage. The number, rated capacity, injection volume, and expansion time of embedded expanders were recorded. The occurrences of complications including infection, hematoma, ulceration of expanded flap after the first stage operation, and blood supply disorder or necrosis of flap after operation in the second and fourth stages were observed. All the patients were followed up for 1 year at least, and the color of flap, scar of frontal donor site, symmetry of bilateral eyebrows, and the nasal appearance and ventilated function of external nasal tract were observed.Results:A total of 26 expanders were embedded in 26 patients. The rated capacity of expanders ranged from 100 to 300 mL. The injection volume was 1.0 to 1.5 times of the rated capacity of expanders. The expansion time ranged from 2.5 to 4.0 months, with an average time of 3 months. There were no complications occurred after each operation. The follow-up showed that the color of flap was similar to the normal nasal skin, the scar of frontal region was not obvious, the bilateral eyebrows were basically symmetrical, the nose had excellent appearance, ventilation function of external nasal tract was not affected, while some of the patients had downward rotation or unapparent tip-defining point of nose.Conclusions:Using the flip scar flap to reconstruct the nasal inner lining and pre-expanded frontal flap to reconstruct the nasal skin, without free cartilage transplantation to repair the partial nasal defects can achieve satisfied nasal appearance post operation, without abnormal external nasal ventilation function.

Objective:To investigate the correlation between three-dimensional histogram analysis of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and Gleason score(GS)in prostate cancer(Pca)from two hospital, and its diagnostic efficacy for discriminating low-grade from high-grade Pca.Methods:A total of 102 pathologically confirmed Pca patients in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Traditional Chinese Medical Hospital(TCM Hospital)Affiliated to Zhejiang Chinese Medical University from January 2017 to October 2020 were retrospectively analyzed.The quantitative parameters of Pca, including transport constant(K trans), rate constant(K ep), percent volume of the extravascular extracellular space(V e)and fraction of the Intraplasmic contrast volume(V p), were obtained by manually layer by layer delineating of interested regions of all lesions on the original DCE-MRI imaging.Then the three-dimensional histogram analysis of the above parameters were performed to obtain the minimum, maximum, median, mean, area, 10 thpercentile, 25 thpercentile, 75 thpercentile and 90 thpercentile.The correlations between quantitative parameters and GS, and diagnostic efficiencies were analyzed. Results:102 Pca patients were divided into low-grade prostate cancer group(GS≤3+ 4)(n=44)and high-grade Pca group(GS≥4+ 3)(n=58). There were no statistically significant differences in age and location of lesions between the two groups( P>0.05), but there were statistically significant differences in Gleason score, PSA level and lesion diameter between the two groups( U=0.000, 730.000, 711.000, all P<0.05). The median, mean, 10 thpercentile, 25 thpercentile, 75 thpercentile, 90 thpercentile derived from K trans, and K ep(median, mean, 10%, 25%, 75%, 90%)together with maximum of K transand mean for V e were positively correlated with GS( r=0.405 to 0.583, P<0.05), in which mean of K transhad the highest positive correlation( r=0.583, P=0.000). The histogram parameters derived from V pwere negatively correlated with GS( r=-0.301 to 0.341, P<0.05). The area under ROC of 75th percentile derived from K transwas the highest(0.832). When the cut-off value of 75 thpercentile derived from K transwas ≥0.680/min, its Youden index, sensitivity, and specificity were 0.594, 0.776, 0.818, respectively. Conclusions:The three-dimensional histogram of DCE-MRI quantitative parameters has correlation with GS in Pca patients, can be used to discriminate low-grade from high-grade Pca.