Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To study the pharmacokinetic characteristic and evaluate the bioequivalence of pregabalin capsules in healthy human plasma under fasting and fed conditions,between the test and reference formulations of pregabalin.Methods Twenty-four healthy volunteers were recruited for fasting and fed conditions,respectively,using single center,randomized,open,two-cycle,two-sequence,double-crossover design,a single oral dose of pregabalin capsule is administrated at 150 mg for test preparation(T)and reference preparation(R),and the washout period is 5 days.The concentration of pregabalin in plasma were determined by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)platform.The pharmacokinetic parameters for each formulation were calculated by Phoenix WinNonlin version 8.0(Pharsight Corporation)using the non-atrioventricular model estimation and analysis,and the bioequivalence was evaluated in the study.Results The main pharmacokinetic parameters of a single oral pregabalin capsule under fasting condition for T and R were as follows:Cmax were(6 180.00±1 170.00)and(6 020.00±1 230.00)ng·mL-1;tmax were 0.75(0.50,1.25)and 0.75(0.50,2.00)h;t1/2 were(5.88±0.82)and(5.96±1.11)h;AUC0-t were(30 921.28±5 156.41)and(30 831.40±5 103.43)ng·mL-1·h.The 90％confidence interval for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ of T and R under fasting condition were 94.79％-110.42％,97.76％-102.87％and 97.13％-102.87％,respectively.The main pharmacokinetic parameters of a single oral pregabalin capsule under fed condition for T and R were as follows:Cmax were(3 430.00±399.00)and(3 460.00±444.00)ng·mL-1;tmax were 3.50(2.00,4.00)and 3.50(1.33,4.00)h;t1/2 were(6.06±0.96)and(6.06±1.06)h;AUC0-,were(28 999.76±3 309.61)and(29 210.75±3 121.60)ng·mL-1·h.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of T and R under fed condition were 95.83％-102.98％,97.62％-100.83％and 97.33％-101.39％,respectively.Conclusion Under fasting and fed conditions,the pregabalin capsule test preparation and the pregabalin capsule reference preparation were bioequivalent in Chinese healthy subjects.

Objective To study the pharmacokinetic characteristic and evaluate the bioequivalence of pregabalin capsules in healthy human plasma under fasting and fed conditions,between the test and reference formulations of pregabalin.Methods Twenty-four healthy volunteers were recruited for fasting and fed conditions,respectively,using single center,randomized,open,two-cycle,two-sequence,double-crossover design,a single oral dose of pregabalin capsule is administrated at 150 mg for test preparation(T)and reference preparation(R),and the washout period is 5 days.The concentration of pregabalin in plasma were determined by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)platform.The pharmacokinetic parameters for each formulation were calculated by Phoenix WinNonlin version 8.0(Pharsight Corporation)using the non-atrioventricular model estimation and analysis,and the bioequivalence was evaluated in the study.Results The main pharmacokinetic parameters of a single oral pregabalin capsule under fasting condition for T and R were as follows:Cmax were(6 180.00±1 170.00)and(6 020.00±1 230.00)ng·mL-1;tmax were 0.75(0.50,1.25)and 0.75(0.50,2.00)h;t1/2 were(5.88±0.82)and(5.96±1.11)h;AUC0-t were(30 921.28±5 156.41)and(30 831.40±5 103.43)ng·mL-1·h.The 90％confidence interval for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ of T and R under fasting condition were 94.79％-110.42％,97.76％-102.87％and 97.13％-102.87％,respectively.The main pharmacokinetic parameters of a single oral pregabalin capsule under fed condition for T and R were as follows:Cmax were(3 430.00±399.00)and(3 460.00±444.00)ng·mL-1;tmax were 3.50(2.00,4.00)and 3.50(1.33,4.00)h;t1/2 were(6.06±0.96)and(6.06±1.06)h;AUC0-,were(28 999.76±3 309.61)and(29 210.75±3 121.60)ng·mL-1·h.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of T and R under fed condition were 95.83％-102.98％,97.62％-100.83％and 97.33％-101.39％,respectively.Conclusion Under fasting and fed conditions,the pregabalin capsule test preparation and the pregabalin capsule reference preparation were bioequivalent in Chinese healthy subjects.

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

To make up for the shortcomings of traditional mild moxibustion, according to the principle and technical operation characteristics of traditional mild moxibustion, combined with temperature control technology, a novel infrared mild moxibustion device is developed, which is capable of real-time accurate temperature control. This novel infrares mild moxibustion device is composed of a host computer and an infrared radiation head. The host computer includes four modules: power supply, human-computer interaction interface, micro control unit (MCU) and drive circuit. The infrared radiation head mainly includes an infrared heater and a temperature sensor. This novel infrared mild moxibustion device is easy to operate. The electrothermal heating tablet can generate infrared radiation of 3 000-13 000 nm. After the temperature of the infrared heater is stabilized, the range of temperature change is ±0.50 ℃, realizing the goal of precise temperature control. In addition, it can operate moxibustion treatment at multiple acupoints at the same time, which is conducive to the dose-effect evaluation of mild moxibustion.
Humans ; Moxibustion ; Acupuncture Points ; Temperature ; Heating

A user-friendly teaching software for visual analysis of acupoint compatibility laws has been developed based on the principles of partial order mathematics. This software is designed to provide auxiliary teaching of structured organization and visualization of law knowledge of compatibility data of acupuncture and moxibustion prescriptions from ancient texts, textbooks, and clinical case records. The software is installed as a plugin in the Microsoft Office Excel, allowing the generation of visually appealing graphs and associated rules that align with the cognitive patterns of teachers and students majoring in acupuncture and moxibustion. Its aim is to facilitate the discovery and analysis of underlying patterns and structured knowledge embedded in acupoint compatibility data, thus contributing to the enhancement of teaching effectiveness in acupoint compatibility.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Moxibustion ; Acupuncture ; Software ; Meridians

Bibliometric and scientific knowledge graph methods were used to analyze the research status and hot spots of acupuncture-moxibustion in treatment of myofascial pain syndrome (MPS) and explore its development trend. The articles of both Chinese and English versions relevant to MPS treated by acupuncture-moxibustion were searched in CNKI, VIP, Wanfang, SinoMed and WOS from the database inception to March 20, 2023. Using Excel2016, CiteSpace6.2.R2 and VOSviewer1.6.18, the visual analysis was conducted by means of the cooperative network, keyword co-occurrence, keyword timeline, keyword emergence, etc. From Chinese databases and WOS database, 910 Chinese articles and 300 English articles were included, respectively. The annual publication volume showed an overall rising trend. Literature output of English articles was concentrated in Spain, China, and the United States, of which, there was less cross-regional cooperation. In the keyword analysis, regarding acupuncture-moxibustion therapy, Chinese articles focused on "acupuncture", "electroacupuncture" and "acupotomy"; while, "dry needling" and "injection" were dominated for English one. Clinical study was the current hot spot in Chinese databases, in comparison, the randomized controlled double-blind clinical trial was predominant in WOS. Both Chinese and English articles were limited in the report of mechanism research. The cooperation among research teams should be strengthened to conduct comparative research, dose-effect research and effect mechanism research with different methods of acupuncture-moxibustion involved so that the evidences can be provided for deeper exploration.
Humans ; Moxibustion ; Pattern Recognition, Automated ; Acupuncture Therapy ; Myofascial Pain Syndromes/therapy* ; Electroacupuncture