The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective To systematically analyze the medical radiation exposure levels in a district of Ningbo City and to provide a scientific basis for the reasonable and effective control of medical radiation exposure. Methods Based on the radiological diagnosis frequency and dose information system, basic medical radiation exposure data were collected, such as radiation doses received by patients in various X-ray diagnostic examinations, from all 13 public medical institutions in a district of Ningbo City from January 1 to December 31, 2020. The data were analyzed for the percentage and collective effective dose of various diagnostic examinations, the distribution of examinations by sex and age, and the number of patients undergoing two or more examinations and their cumulative doses within multiple time intervals. Results Among medical X-ray diagnostic examinations in the district, the percentages of CT examination and routine photography examination were 50.88% and 47.93%, respectively, and the collective effective dose of CT examination accounted for 97.75%. By age and sex, the frequency of examination was the highest in the age group of 45-54 years, and the frequency of examination in the male was higher than that in the female before age 55. The annual effective dose for two patients exceeded 100 mSv. Conclusion In this study, CT examination accounted for up to 50.88% of all medical X-ray diagnostic examinations, and contributed 97.75% of the collective effective dose, highlighting the need for particular attention to the justification of medical radiation exposure from CT.

Objective To observe the application effect and safety of continuous adductor canal block(ACB)with different doses of dexmedetomidine(DEX)combined with ropivacaine in postoperative analgesia of total knee arthroplasty(TKA).Methods Patients with TKA were enrolled as the research subjects and were divided into low-dose group,middle-dose group and high-dose group by the random number table method.At 10 min before induction of general anesthesia,all the groups were given 20 mL of 0.5％ropivacaine loading dose for ACB,placed nerve block indwelling catheter,and started ACB analgesia pump after the end of surgery.Low-dose group,middle-dose group and high-dose group were given 0.5,1.0 and 1.5 μg·kg-1 DEX+0.25％ropivacaine for a total of 100 mL,with a background dose of 4 mL·h-1and a control dose of 4 mL,and they locked for 30 min and continuously treated for 48 h.The surgical parameters and postoperative recovery quality of the two groups were compared.Visual analogue scale(VAS)was used to evaluate the pain status in resting state and motion state at 2,6,12,24 and 48 h after surgery.The number of effective compressions of self-controlled analgesia pump and the dosage of remedial analgesics at 48 h after surgery were counted and the safety evaluation was performed.Results No cases dropped out during treatment,and finally 30 cases were included in low-dose,middle-dose and high-dose groups,respectively.The first ambulation times in low-dose,middle-dose and high-dose groups were(54.22±8.37),(47.68±7.65)and(52.79±8.74)h;the time of active knee flexion 90° were(8.90±3.10),(7.20±2.70)and(8.60±2.40)d;the motion VAS scores were(3.86±0.59),(3.57±0.51)and(3.48±0.52)points at 48 h after surgery;the times of first analgesia pump compression within 48 h after surgery were(10.57±3.87),(12.45±3.63)and(13.36±3.56)h;the number of effective compressions of self-controlled analgesia pump were(6.11±2.18),(3.76±1.14)and(3.24±1.07)times;the remedial analgesia rates were 13.33％,0 and 0;at 6 h after surgery,quadriceps muscle strength scores were(4.81±0.21),(4.75±0.23)and(4.61±0.26)points,and the incidence rates of adverse drug reactions were 20.00％,6.67％and 6.67％,respectively.There were statistically significant differences in the above indicators between low-dose group and middle-dose group except for the incidence of adverse drug reactions(all P＜0.05).There were statistical differences between low-dose group and high-dose group except for the incidence of adverse drug reactions(all P＜0.05),but there were no statistical differences between middle-dose group and high-dose group(all P＞0.05).Conclusion The use of 1.0 μg·kg-1DEX combined with ropivacaine for ACB in TKA patients can achieve good postoperative analgesia effect and it has small impact on muscle strength and has good safety,thus this dose can be used as a clinical recommended dose.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.

The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions. In this study, the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material, which provided a sufficient basis for determining the formulation and process of solid dispersions. The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4. If the ratio is greater than 1∶ 4, the glass transformation temperature of the material will increase significantly, and the solubilization effect of the solid dispersion will show a downward trend. The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150 ℃, the viscosity of the material is less than 10 000 Pa·s, and the melt can be extruded smoothly, and the best extrusion temperature of 160-180 ℃ can be obtained by combining the dissolution results. Finally, the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra. Therefore, rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level, which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

Microsporidia is a group of intracellular parasitic eukaryotic microorganisms that pose threats to livestock fish production and human health, but there is no special chemo-therapeutic drug available for the treatment of microsporidia currently. In this study, sulfonamide derivatives of spectinomycin were designed by taking into consideration the low toxicity of spectinomycin and the favorable pharmaceutical properties of sulfonamides. Through the exploration of reaction conditions, a total of 21 target molecules were synthesized with a yield of 52%-74% and their chemical structures were confirmed by ¹H NMR, ¹³C NMR, and high resolution mass spectrometry (HR MS). By screening in vitro, the host cell cytotoxicity and biological activity of target molecules to Encephalitozoon hellem, a representative of vertebrates infecting microsporidia, were studied. It was found that four target molecules each could inhibit or promote the proliferation of E. hellem. In this study, the synthesis method of sulfonamide derivatives of spectinomycin was established, and new compounds effective against E. hellem were discovered, which provided a new idea for the further derivatization of spectinomycin and the development of therapeutic drugs targeting microsporidia.