This case report describes a 68-year-old male patient diagnosed with primary hepatocellular carcinoma (HCC). After receiving Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT), the tumor significantly reduced in size, and tumor markers alpha fetoprotein (AFP) and abnormal prothrombin (PIVKA-Ⅱ) decreased. Postoperative pathological results showed minimal residual tumor cells, indicating that ⁹⁰Y-SIRT has good efficacy and safety in downstaging and conversion of HCC, thereby facilitating subsequent surgical resection.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Objective To assess the risk of human Spirometra mansoni infections and investigate the knowledge, attitude and practice (KAP) towards sparganosis mansoni among residents in Henan Province, so as to provide insights into formulation of the sparganosis mansoni control measures. Methods Qinling Village in Fugou County of Zhoukou City, Bali Village in Yancheng District of Luohe City, Duzhai Village in Puyang County of Puyang City and Doushan Village in Luoshan County of Xinyang City were sampled as survey sites in Henan Province from July to August 2023, and more than 40 frogs were sampled from ponds or streams in each survey site for detection of Sparganum mansoni infections. At least 150 residents were sampled using a cluster sampling method from each survey site, and the sero-prevalence of anti-S. mansoni IgG antibody was estimated. In addition, a questionnaire survey was conducted on the KAP towards sparganosis mansoni among participants, and the proportion of eligible KAP, rate of correct KAP and KAP scores were calculated. Results A total 229 frogs were collected from 4 survey sites in 2023, and the overall prevalence of S. mansoni infection was 4.37% (10/229) in frogs, with 7.75% (10/129) prevalence in wild frogs and 0 in farm-bred frogs. A questionnaire survey was performed among 649 residents sampled from 4 survey sites, and 649 serum samples were collected. The seroprevalence of anti-S.mansoni IgG antibody was 0.15% (1/649) and the overall proportion of eligible KAP was 23.73% (154/649) among participants. There were age- (χ² = 30.905, P = 0.000), educational level- (χ² = 41.011, P = 0.000), and occupation-specific proportions of eligible KAP among participants (χ² = 10.721, P = 0.005), and the proportion of eligible KAP decreased with age (χ² _trend = 22.717, P = 0.000) and increased with education levels (χ² _trend = 40.025, P = 0.000). The rates of correct KAP towards sparganosis mansoni were 40.81% (2 119/5 192), 96.66% (1 882/1 947) and 63.81% (3 727/5 841) (χ² = 1 913.731, P = 0.000) among residents, respectively. The rates of correct KAP towards sparganosis mansoni varied significantly among survey sites (χ² = 136.872, 42.347 and 255.157; all P values= 0.000, with the highest rate of correct knowledge (51.94%, 748/1 440) and practices (75.86%, 1 229/1 620) in Yancheng District of Luohe City and the highest rate of correct attitudes in Puyang County of Puyang City (99.11%, 446/450) (all P values< 0.05). Conclusions There is still a high transmission risk of sparganosis mansoni in Henan Province, and the KAP towards sparganosis mansoni is required to be improved among residents.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.