BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

Objective:To investigate the anxiety and depression of elderly patients with lung cancer before and after chemotherapy.Methods:A total of 168 elderly patients diagnosed with lung cancer and eligible for chemotherapy in a Grade A tertiary hospital in Shenyang from Jan 2022 to Feb 2024 were selected as the study subjects.The basic data,self-rating depression scale(SDS),and self-rating anxiety scale(SAS)scores before and after chemotherapy were collected.The Spearman rank correlation test was used to analyze the correlation of the general data of patients with SDS and SAS scores before and after chemotherapy.Results:SDS and SAS scores of lung patients after chemotherapy were significantly higher than those before chemotherapy(P＜0.05).The proportion of patients with depression and anxiety after chemotherapy was also significantly higher than that before chemotherapy(P＜0.05).Results of Spearman's rank correlation test showed that,the increase of SDS and SAS scores was correlated with gender,pathological type,chemotherapy cycle,combined underlying diseases,and respiratory symptoms(P＜0.05).Conclusions:Chemotherapy increases the proportion of anxiety and depression in elderly patients with lung cancer.Gender,pathological type,chemotherapy cycle,combined underlying diseases,and respiratory system symptoms are correlated with the occurrence of anxiety and depression.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination