Objective:To explore the impact of socioeconomic status on disability among middle-aged and elderly individuals in China.Methods:This was a retrospective cohort study. At the baseline year of 2011, 14 213 individuals aged 45 years and above from the China Health and Retirement Longitudinal Study were consecutively selected, and their repeated measurement data with complete information from the 4 rounds of follow-up from 2013 to 2020 were consecutively selected, with a total of 67 355 cases included in the analysis. The principal component analysis was used to construct a socioeconomic status index (SESI) and the generalized estimating equation was employed to analyze the association between the SESI and disability in the participants. And the impact of SESI on disability in different age subgroups was further analyzed.Results:Among the 14 213 participants included in the 2011 baseline sample for analysis, there were 6 833 males and 7 380 females, 7 953 aged 45-60 years, 5 156 aged 61-75 years, and 1 104 aged over 75 years. Additionally, there were 3 812 with high SESI, 4 526 with medium SESI, and 5 875 with low SESI. The incidences of disability were greater in the individuals aged>75 years, females, and those with a low SESI (all P<0.05). The risk of incidence of disability in the middle-aged and elderly population increased with decrease of SESI (medium SESI: OR=1.47, 95% CI: 1.39-1.55; low SESI: OR=1.79, 95% CI: 1.69-1.89) (all P<0.001). The difference in the risk of disability in the middle-aged and elderly individuals across the different SESI was greatest at 45-60 years ( OR=2.08, 95% CI: 1.91-2.26), which gradually decreased with increasing age and was smallest at>75 years (OR=1.33, 95% CI: 1.09-1.61) (all P<0.001). Conclusions:The lower the socioeconomic status of China′s middle-aged and elderly individuals, the higher the incidence of disability; the impact of socioeconomic status on risk of disability is more pronounced in the early years of middle and old age and gradually decreases with age.

Objective:To explore the impact of socioeconomic status on disability among middle-aged and elderly individuals in China.Methods:This was a retrospective cohort study. At the baseline year of 2011, 14 213 individuals aged 45 years and above from the China Health and Retirement Longitudinal Study were consecutively selected, and their repeated measurement data with complete information from the 4 rounds of follow-up from 2013 to 2020 were consecutively selected, with a total of 67 355 cases included in the analysis. The principal component analysis was used to construct a socioeconomic status index (SESI) and the generalized estimating equation was employed to analyze the association between the SESI and disability in the participants. And the impact of SESI on disability in different age subgroups was further analyzed.Results:Among the 14 213 participants included in the 2011 baseline sample for analysis, there were 6 833 males and 7 380 females, 7 953 aged 45-60 years, 5 156 aged 61-75 years, and 1 104 aged over 75 years. Additionally, there were 3 812 with high SESI, 4 526 with medium SESI, and 5 875 with low SESI. The incidences of disability were greater in the individuals aged>75 years, females, and those with a low SESI (all P<0.05). The risk of incidence of disability in the middle-aged and elderly population increased with decrease of SESI (medium SESI: OR=1.47, 95% CI: 1.39-1.55; low SESI: OR=1.79, 95% CI: 1.69-1.89) (all P<0.001). The difference in the risk of disability in the middle-aged and elderly individuals across the different SESI was greatest at 45-60 years ( OR=2.08, 95% CI: 1.91-2.26), which gradually decreased with increasing age and was smallest at>75 years (OR=1.33, 95% CI: 1.09-1.61) (all P<0.001). Conclusions:The lower the socioeconomic status of China′s middle-aged and elderly individuals, the higher the incidence of disability; the impact of socioeconomic status on risk of disability is more pronounced in the early years of middle and old age and gradually decreases with age.

Objective:To analyze the significance of total vitamin D(tVD),total procollagen type Ⅰ amino-terminal propeptide(tPINP)and β-CrossLaps(β-CTx)in the staging and prognosis of patients with multiple myeloma(MM).Methods:A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group(MM group),and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group.The expression levels of tVD,tPINP and β-CTx in the two groups were detected by chemiluminescence method.The differences in the expression levels of tVD,tPINP and β-CTx among MM patients at different ISS stages were analyzed.The expression levels of tVD,tPINP and β-CTx in MM patients with different levels of hemoglobin(Hb),serum calcium(Ca),creatinine(Crea),albumin(ALB),β2-microglobulin(β2-MG)and lactate dehydrogenase(LDH)were compared.The correlations between the expression levels of tVD,tPINP,β-CTx and the aforementioned clinical parameters were analyzed,respectively.The relationship between the expression levels of tVD,tPINP,β-CTx and the progression-free survival(PFS)of MM patients was analyzed.Results:The expression level of tVD in the MM group was significantly lower than that in the control group(21.73±14.45 ng/ml vs 30.78±9.94 ng/ml,P=0.022).The expression level of β-CTx in the MM group was significantly higher than that in the control group(1.43±0.99 ng/ml vs 0.53±0.29 ng/ml,P=0.013).The tVD level in MM patients with ISS stage Ⅰ-Ⅱ was significantly higher than that of MM patients with ISS stage Ⅲ(29.50±14.59 ng/ml vs 12.62±7.73 ng/ml,P=0.028),indicating that the higher the ISS stage,the lower the tVD level.The tPINP andβ-CTx levels in MM patients with high Ca levels(＞2.65 mmol/L)were significantly higher than those in patients with low Ca levels(≤ 2.65 mmol/L)(P=0.016,P=0.021).The tVD level of MM patients was positively correlated with the ALB level(r=0.570),tPINP was positively correlated with Ca and β2-MG levels(r=0.791,r=0.673),and β-CTx was positively correlated with tPINP level(r=0.616).The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group(P=0.041).Conclusion:The expression level of tVD is decreased in MM patients,which can be used as an indicator to evaluate the disease stage and prognosis of the patients.The β-CTx expression level is increased in MM patients.tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

In this study, deep eutectic solvents (DESs) were used as excipients to prepare solid dispersion (SD) of scutellarin. The SD of scutellarin were prepared by melting method with cumulative dissolution rate as the index of investigation. The preparation conditions of SD of scutellarin were optimized by single factor experiment, which investigated the type of the carrier material, the type of DESs, and the ratio of the drug to the carrier. The optimum preparation conditions of DESs-SD were as follows: using Poloxamer 407 as the carrier material, PEG 200/urea (2∶1) as the DESs system, and the ratio of carrier, DESs, and drug was 6∶1∶1. The drug loading capacity of scutellarin in SD was 12.53% under the optimum preparation conditions. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscope exhibited that scutellarin was amorphous form in the SD system. Furthermore, the stability of the DESs-based SD of scutellarin was evaluated by high temperature, high humidity, and strong light tests, which showed that the cumulative dissolution rate and scutellarin content of SD decreased with time under these conditions. Finally, the result of pharmacokinetic studies indicated that the oral absorption of the scutellarin could be increased using DESs as an excipient in the preparation of SD. The animal experiment was approved by the Experimental Animal Ethics Committee of Fujian University of Traditional Chinese Medicine (approval number: FJTCMIACUC 2023048). Consequently, this research offers a novel and effective approach for using DESs to enhance the oral bioavailability of active substances with low water solubility.

Objective:To develop and validate a model to predict the risk of malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. Methods:From April 2022 to August 2023, 430 patients with nasopharyngeal carcinoma who were admitted to the department of radiotherapy of the first affiliated hospital of Guangxi medical university in Nanning were conveniently selected as the study subjects, and they were divided into the modelling group (300 cases) and the internal validation group (130 cases) in the internal validation group in the ratio of 7:3, and 61 patients with nasopharyngeal carcinoma admitted to the affiliated cancer hospital of Guangxi medical university in Nanning City were selected as the external validation group. Logistic regression was used to establish the risk prediction model and draw nomograms,Hosmer-Lemeshow, calibration curve and ROC were used to verify the goodness of fit and predictive power of the model, and clinical decision curve was used to assess the clinical utility. Results:Logistic regression analysis showed that skeletal muscle mass index, self-rated anxiety scale score, Pittsburgh sleep quality questionnaire score, Chinese diet pagoda score, regular exercise, and digestive symptom groups were the influencing factors for malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. In the modelling group, the area under the ROC curve was 0.853 (95％CI:0.81 ～ 0.89), the maximum Youden was 0.600, and the corresponding specificity was 0.764 and the sensitivity was 0.836. The Hosmer-Lemeshow test=4.040 and P=0.853 indicated that the model had good predictive ability. Calibration curve of the calibration showed that the predictive effect of the model matched actual probability well, with an average absolute error was 0.024. When the threshold probability of the clinical decision curve is 0.05 ～ 0.85, the clinical response rate is higher. The area under the operating curve of the subjects in the internal validation group was 0.891, the sensitivity was 77.36％, the specificity was 89.61％, and the practical application accuracy was 84.62％. The area under the operating curve of the subjects in the external validation group was 0.886, the sensitivity was 76.00％, the specificity was 83.33％, and the overall accuracy was 80.33％. Conclusion:The risk prediction model constructed in this study has a good effect, which can effectively predict the incidence of malnutrition in patients receiving concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma, and provide a reference for clinical staff to formulate and implement nutritional interventions.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.

Aim To evaluate the effect of Pien Tze Huang(PTH)on influenza virus susceptibility in re-straint stress-induced H1N1 influenza susceptibility model in mice with emotional disorders and internal heat,guided by the theory of emotional pathogenesis.Methods Mice were infected with H1N1 influenza vi-rus following 18 h of restraint stress.The signs and weight changes of mice were recorded,and the morbid-ity of mice were analyzed.On the fourth day post viral infection,the lung tissue was collected.The pathologi-cal changes and inflammatory factors in lungs were de-tected by HE staining.The expression of NP was as-sessed by immunohistochemistry and Western blot.The level of lipid peroxidation end products was detected u-sing a commercial kit and western blot.Redox phos-pholipidomics was analyzed in lung tissue by HPLC-MS/MS.Results PTH significantly reduced the mor-tality of influenza-susceptible mice induced by emotion-al stress,inhibited the expression of NP and the re-lease of inflammatory factors,improved inflammation in lung tissue,and alleviated the accumulation of lipid peroxidation end products.Phospholipid oxidation a-nalysis revealed the elevated levels of oxidized phos-pholipid choline and phosphatidylethanolamine in lung tissue of influenza-susceptible mice,which were signif-icantly reduced by PTH administration.Conclusions PTH exhibits promising efficacy in ameliorating influ-enza virus susceptibility induced by internal heat,and its mechanism of action may be related to the regulation of phospholipid peroxidation.

AIM To study the chemical constituents from the n-butanol fraction of Siegesbeckiae glabrescens Makino.METHODS The n-butanol fraction from S.glabrescens was isolated and purified by silica gel,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Seventeen compounds were isolated and identified as orientalin B(1),ent-2-oxo-15,16,19-trihydroxypimar-8(14)-ene(2),ent-12α,16-epoxy-2β,15α,19-trihydroxypimar-8-ene(3),ent-12α,16-epoxy-2β,15α,19-trihydroxy-pimar-8(14)-ene(4),kirenol(5),benzyl-O-β-D-glucopyranoside(6),hexyl-β-glucopyranoside(7),(Z)-3-hexenyl-β-D-glucopyranoside(8),phenylethyl-O-β-D-glucopyranoside(9),(6R,9S)-3-oxo-α-ionol-β-D-glucopyranoside(10),2-methoxy-4-(2-propenyl)phenyl-β-D-glucoside(11),4-allyl-2,6-dimethoxyphenyl glucoside(12),2-hydroxy-methylphenyl-1-O-β-D-glucopyranoside(13),icarside B2(14),everlastoside D(15),(2S,4R,5S,7S,9S,10R,13S,15R)-2,7,15,16,19-pentahydroxypimar-8(14)-ene(16),and benzyl-β-D-apiofuranosyl-(1″→6′)-β-D-glucopy-ranoside(17).Compound 9 showed weak ABTS radical scavenging capability,and compound 15 had strong DPPH and ABTS radicals scavenging activities.CONCLUSION Compounds 7-9,14-15 are isolated from genus Siegesbeckia for the first time.Compounds 2-4,7-17 are first isolated from this plant.Compound 9 and 15 exhibit antioxidant activities.

Tripterifordin and neotripterifordin are important ent-kaurane diterpenoids in the Chinese medicinal herb Tripterygium wilfordii, possessing significant anti-HIV(human immunodeficiency virus) activity. On the basis of elucidating the natural biosynthetic pathways of these compounds, heterologous production with microbial cell factories can help to alleviate the reliance on plant resources and provide abundant raw materials for sustainable production. TwKO is the first CYP450 enzyme involved in the biosynthesis of tripterifordin and neotripterifordin. This study aimed to enhance the catalytic activity of TwKO by site-directed mutagenesis to benefit the production of tripterifordin and neotripterifordin in yeast. The AlphaFold DB established based on the AlphaFold 2 was employed to obtain the protein model of TwKO. According to multiple sequence alignments and principles of natural evolution, the key residues influencing the binding of TwKO to the substrate were identified. Subsequently, functional characterization of the mutants were conducted in Saccharomyces cerevisiae. A total of 71 mutants were obtained, among which 11 and 11 mutants had the abilities of enhancing the production of 16α-hydroxy-ent-kaurenol and 16α-hydroxy-ent-kaurenoic acid, respectively. In addition, 10 mutants could increase the proportion of the oxidation product of 16α-hydroxy-ent-kaurenol. In particular, R304 was identified as a key residue affecting the catalytic specificity of TwKO, the mutation of which led to the specific prodiction of 16α-hydroxy-ent-kaurenol. This study was the first to reveal the key residue affecting the catalytic activity of TwKO and obtained the mutants with increased TwKO activity, lay a foundation for the biosynthesis of tripterifordin and neotripterifordin.
Tripterygium/chemistry* ; Mutagenesis, Site-Directed ; Diterpenes, Kaurane/chemistry* ; Plant Proteins/chemistry* ; Cytochrome P-450 Enzyme System/chemistry* ; Saccharomyces cerevisiae/metabolism*