INTRODUCTION: Odour recognition is influenced by culture. Odour identification tests need to be adapted to a population to accurately assess olfactory function. This study's objectives were to validate the Singapore version of the Sniffin' Sticks (SS-Sg) and a locally-developed odour recognition test (Scentsor) for Singapore. METHOD: This prospective study was performed in 3 otolaryngology outpatient clinics in 3 phases (1 May to 15 November 2024). Phase 1 was a survey evaluation of 93 odour descriptors to identify familiar odour descriptors to be used in the tests (n=414); Phase 2 evaluated and finalised SS-Sg and Scentsor to ensure test odours were recognised by ≥75% of healthy controls (n=130); and Phase 3 validated both tests on healthy controls (n=473) to obtain normative data, to determine test-retest reliability (n=50), and to assess the ability to distinguish patients with olfactory loss (n=67). RESULTS: In Phase 1, the unmodified SS blue and purple sets had 15/32 (46.9%) unfamiliar test odours and 25 unfamiliar distractors combined. In Phase 2, after modification, all odours in SS-Sg and Scentsor were correctly identified by ≥75% of controls. In Phase 3, normative data (age 21-83 years) was obtained. Both tests had good test-retest reliability (Pearson's correlation coefficient of 0.88 with<0.001 for SS-Sg; and at 0.90 with<0.001 for Scentsor). Both tests differentiated among normosmia, hyposmia and anosmia (SS-Sg scores: 12.6 [±2.4] versus [vs] 9.8 (±3.2) vs 6.0 [±2.3] respectively,<0.001; Scentsor scores: 14.3 [±1.8] vs 11.3 [±2.8] vs 5.8 [±3.4] respectively,<0.001). CONCLUSION SS-Sg and Scentsor have been validated to assess olfaction in Singapore.
Humans ; Singapore ; Male ; Female ; Odorants/analysis* ; Middle Aged ; Prospective Studies ; Olfaction Disorders/diagnosis* ; Adult ; Reproducibility of Results ; Aged ; Smell/physiology* ; Young Adult

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

OBJECTIVE: To explore clinical effect of reverse shoulder replacement in treating giant irreparable rotator cuff tear complicated with glenohumeral arthritis. METHODS: A retrospective analysis was performed on 18 patients (18 shoulders) with glenohumeral arthritis combined with large irreparable rotator cuff tear admitted from April 2020 to April 2022, including 10 males and 8 females, aged from 60 to 78 years old;7 patients on the left side, 11 patients on the right side;the course of disease ranged from 6 to 21 months;7 patients with grade 3 and 11 patients with grade 4 according to Goutallier grading;8 patients with grade 4b and 10 patients with grade 5 according to Hamada grading. Shoulder joint motion, visual analogue scale (VAS), University of California at Los Angeles (UCLA) score and Constant-Murley shoulder joint function score and complications were compared at the latest follow-up. RESULTS: Eighteen patients were followed up for 24 to 48 months. At the latest follow-up, shoulder joint flexion ranged from 120° to 145°, abduction ranged from 100° to 130°, and rotation ranged from 45° to 60°. VAS ranged from 1 to 3;Constant-Murley score ranged from 80 to 95;and UCLA scores ranged from 27 to 35, and 6 patients obtained excellent result, 11 good and 1 average. Dislocation of shoulder joint occurred in 1 patient at 3 months after operation, but no dislocation occurred after manual reduction. The incision surface infection occurred in 1 patient at 1 week after operation, and the incision healed after anti-infection and cleaning. The other patients did not have complications such as dislocation, infection, prosthesis loosening and peripheral fracture. CONCLUSION Reverse shoulder replacement for the treatment of huge irreparable rotator cuff injury combined with glenohumeral arthritis disease, the clinical effect is good, could significantly improve shoulder joint function and improve quality of life, but still need to strengthen the prevention and treatment of postoperative complications such as dislocation and infection.
Humans ; Male ; Female ; Middle Aged ; Rotator Cuff Injuries/physiopathology* ; Aged ; Retrospective Studies ; Arthroplasty, Replacement, Shoulder/methods* ; Range of Motion, Articular ; Shoulder Joint/physiopathology*

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective:To investigate the effects of down-regulation of p21 activated kinase 1(PAK1)on the proliferation,differentiation,and apoptosis of myeloproliferative neoplasm(MPN)cells(6133/MPL)with thrombopoietin receptor MPL mutation at codon 515(MPLW515L)and survival of 6133/MPL mice.Methods:Interference with the protein level of PAK1 in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology.CCK-8 assay was used to detect the effect of down-regulation of PAK1 on the proliferation viability of 6133/MPL cells,and colony-forming ability was measured by cell counting.Flow cytometry was used to detect the PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in 6133/MPL cells.The expression of cyclin D1,cyclin D3 and apoptosis-related protein Bax was detected by Western blot.The infiltration of tumor cells in spleen and bone marrow of 6133/MPL mice were detected by HE staining.Results:Down-regulation of PAK1 inhibited the proliferation and reduced the ability of cell colony formation of 6133/MPL cells.After knocking down PAK1,the content of polyploid DNA in 6133/MPL cells increased from 31.8 to 57.5％and 48.0％,and the proportion of apoptosis increased approximately to 10.8％.Down-regulation of PAK1 led to a reduction of infiltration of tumor cells in liver and bone marrow of 6133/MPL mice,thereby prolonging survival time.Conclusion:Down-regulation of PAK1 can significantly inhibit the growth of 6133/MPL cells,promote the formation of polyploid DNA,induce 6133/MPL cell apoptosis,and prolong the survival time of 6133/MPL mice.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P＜0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P＜0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P＜0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P＜0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.