OBJECTIVE To systematically identify the dilemmas in value assessment of antitumor combination therapies， and to provide evidence for health insurance coverage， drug pricing， and clinical decision-making. METHODS The concept of “surplus value space” was introduced to cons truct a value assessment framework， under which the dilemmas in three assessment scenarios were analyzed. Optimization recommendations were proposed by drawing on international research addressing similar challenges. RESULTS & CONCLUSIONS The core dilemma of value assessment for antitumor combination therapies lies in insufficient surplus value space. When the cost of the backbone therapy exceeds its corresponding health value， the add-on drug encounters a “free but uneconomical”problem. Existing international value assessment methods have limitations such as flawed evaluation frameworks， difficulty in operationalizing the quality-adjusted life year allocation framework， and frequent occurrence of the “free but uneconomical”problem， rendering them inadequate for the complex scenarios of antitumor combination therapies. To address these dilemmas， strategies such as adjusting payment thresholds， exploring discounted pricing， conducting multi-product linkage negotiations， and delaying insurance access are recommended to improve the rationality and feasibility of value assessment for antitumor combination therapies.

Objective To evaluate the feasibility and efficacy of the three-guidewire technique for retrograde stent placement in the treatment of ureteral mucosal sleeve avulsion (UMSA). Methods A retrospective analysis was conducted on the clinical data of 12 patients with UMSA secondary to ureteroscopic lithotripsy for ureteral calculi in our hospital during Jul. 2010 and Oct. 2023. The three-guidewire technique was employed for retrograde stent placement during the procedure. A secondary ureteroscopic lithotripsy was performed one month postoperatively.Results Double-J stent was successfully placed in all 12 patients, with a mean stent insertion time of 23.3(16-30)minutes. No intraoperative exacerbation of mucosal avulsion occurred. One patient was lost to follow-up. At the one-month postoperative ureteroscopic examination and lithotripsy, 81.8% (9/11) cases exhibited unobstructed ureters, while 18.2%(2/11) developed annular membranous strictures, which were resolved following dilation. During subsequent follow-up, the postoperative creatinine level after double-J stent removal showed a mild decrease compared to the preoperative level [87.9(72-100)μmol/L vs. 90.1(69-108)μmol/L]. Up to 90.9%(10/11) patients remained free of hydronephrosis, with only 1 case (9.1%) requiring laparoscopic ureterovesical reimplantation for hydronephrosis 4 months postoperatively. Conclusion The three-guidewire technique for retrograde stent placement in the treatment of UMSA demonstrates strong operability, high success rates, favorable outcomes, and a low incidence of ureteral stricture, which warrant wide clinical promotion.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

The gut microbiota is closely related to human health, and various gut microbiota health indices have been developed to assist in evaluating the health of the gut microbiota and even the overall health of the human body. Diets are one of the main factors that regulate the gut microbiota, while there is still no good method for evaluating the regulatory effects of dietary factors. To assess the regulatory effects of dietary factors on the gut microbiota of overweight individuals, we conducted an in vitro fermentation experiment based on 17 dietary factors, and developed an evaluation method for the regulatory effects of dietary factors based on the health index with principal component analysis (hiPCA). The results showed that most dietary factors had positive regulatory effects on the gut microbiota of overweight individuals. Galactooligosaccharides (GOS) and puerarin were the most significant dietary factors in regulating the gut microbiota of overweight individuals. The analysis of the contribution of species to the hiPCA indicated that GOS and puerarin might inhibit the activities of bacteria associated with overweight by regulating Eubacterium dolichum, Lactobacillus salivarius, Clostridium clostridioforme, Clostridium citroniae, and Lachnospiraceae bacterium 9_1_43BFAA. In addition, GOS may further enhance the inhibition of these activities by regulating Lachnospiraceae bacterium 6_1_63FAA, thereby reducing the gut health risks in overweight individuals. In summary, this study evaluated the health effects of dietary factors based on the hiPCA and specifically analyzed the role of different dietary factors in regulating the gut microbiota of overweight individuals. This provides new ideas and methods for improving gut microbiota health and has potential applications in the field of precision nutrition.
Humans ; Gastrointestinal Microbiome/physiology* ; Isoflavones/pharmacology* ; Overweight/microbiology* ; Diet ; Fermentation ; Oligosaccharides/pharmacology* ; Principal Component Analysis

Objective: To analyze the influencing factors for anterior tibial artery atherosclerosis among patients with hyperuricemia, so as to provide insights into the prevention of anterior tibial artery atherosclerosis. Methods: Patients aged 18 years and older with hyperuricemia in Dazhou Integrated TCM & Western Medicine Hospital were enrolled as research subjects from 2020 to 2023. Demographic information and blood biochemistry indicators were collected through electronic medical records. Anterior tibial artery atherosclerosis was evaluated by color Doppler ultrasound. Factors affecting anterior tibial artery atherosclerosis among patients with hyperuricemia were analyzed by a multivariable logistic regression model. Results: A total of 1 105 patients with hyperuricemia were surveyed, including 862 males (78.01%) and 243 females (21.99%). There were 918 cases (83.08%) at the ages of 60 years and older, and 457 cases (41.36%) with a course of disease at 10 years and longer. The median level of blood uric acid was 480.79 (interquartile range, 98.28) μmol/L. There were 314 cases (28.42%) with anterior tibial artery atherosclerosis. Multivariable logistic regression analysis showed that body mass index (≥24.0 kg/m2, OR=1.597, 95%CI: 1.185-2.151), long-term smoking history (yes, OR=1.709, 95%CI: 1.153-2.534), diabetes mellitus (yes, OR=1.517, 95%CI: 1.162-1.981), serum uric acid (≥480.79 μmol/L, OR=1.667, 95%CI: 1.131-2.457), serum creatinine (≥97 μmol/L, OR=1.685, 95%CI: 1.155-2.460), fasting blood glucose (≥6.1 mmol/L, OR=1.528, 95%CI: 1.106-2.112), fibrinogen (>4 g/L, OR=1.589, 95%CI: 1.091-2.315) and triglycerides (≥1.7 mmol/L, OR=1.879, 95%CI: 1.226-2.881) were influencing factors for anterior tibial artery atherosclerosis among patients with hyperuricemia. Conclusion Anterior tibial artery atherosclerosis among patients with hyperuricemia is associated with long-term smoking, diabetes mellitus, serum uric acid, serum creatinine, fasting blood glucose, fibrinogen and triglycerides high level.

BACKGROUND:The healing of mandibular fractures after rigid internal fixation is influenced by many factors,including the material of the bone plate,fracture site,and bone density of the patient.However,there are relatively few studies on the relationship between the stability of mandibular fracture fixation in different bone qualities and they lack a scientific basis. OBJECTIVE:To analyze the stability of fixation of mandibular fractures with different bone qualities with bioabsorbable plates and miniature titanium plates by finite element analysis. METHODS:Three-dimensional finite element models of class Ⅰ-Ⅳ mandibular fractures were developed according to the bone quality classification method proposed by ZARB and LEKHOLM.The fractures at the median mandibular symphysis,mandibular body,and mandibular angle were simulated under different bone qualities.Bioabsorbable bone grafting plates(or miniature titanium plates)were placed at each fracture site for fixation and to simulate the state of healthy side occlusion.Finite element analysis on the model was used to analyze the relative displacement of the fracture segments and the stress distribution of fixators. RESULTS AND CONCLUSION:(1)The maximum stress value during fixation with titanium plates increased gradually with the increase of bone class,in which the maximum stress value of titanium plates was the highest in the mandibular body class Ⅳ bone group,which was 382.74 MPa and 96.11 MPa in the miniature titanium plate and bioabsorbable plate groups.The results for mandibles of the same bone type showed that the maximum stress value of titanium plates was much higher than that of bioabsorbable plates.(2)For fractures of the median middle of the mandible in types Ⅲ and Ⅳ,the displacement of the fracture breaks at the fixation site was large and exceeded the limiting value of bone healing(>150 μm),regardless of whether the fixation was performed with a miniature titanium plate or a bioabsorbable plate.For type Ⅳ mandibular fractures,the fracture end displacement in the bioabsorbable plate group exceeded the healing limit value,and the fracture end displacement in the miniature titanium plate group was close to the healing limit value.Under the same bone quality and fracture site,the fracture displacement of the miniature titanium plate group was smaller than that of the bioabsorbable plate group.(3)The results showed that the strength and stiffness of the two internal fixations were sufficient to support bone healing of fractures at three sites of the types Ⅰ-Ⅳ mandible,and the fixation stability of the bioabsorbable plate was almost the same as that of the miniature titanium plate,which could provide early healing conditions for fractures.Mandibular bone type should be taken into consideration in the treatment of mandibular fracture.The higher the mandibular bone grade,the worse the stability of fracture fixation,and the more likely the complications such as poor bone healing will occur after surgery.

BACKGROUND:Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis,but this may be affected by confounding and reverse causality,and the conclusions have not been unified. OBJECTIVE:To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS:Data from genome-wide association studies associated with different exercise intensities were selected,and instrumental variables were screened with a threshold of P＜5×10-8.Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method.Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis,and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION:In the analysis results of the inverse variance weighting method,low-intensity exercise showed a significant protective effect on knee osteoarthritis[odds ratio(OR)=0.14,95%confidence interval(CI):0.06-0.32,P＜0.001],while sedentary behavior without exercise intensity,such as watching TV,was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis(OR=2.24,95%CI:1.74-2.88,P＜0.001;OR=1.34,95%CI:1.01-1.78,P=0.04).Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities,it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV.The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Objective To analyze the predictive value of preoperative magnetic resonance imaging(MRI)indexes in patients with full thickness rotator cuff tear(FTRCT)undergoing arthroscopic rotator cuff repair(ARCR).Methods Clinical data of 451 patients with FTRCT undergoing ARCR from January 2020 to December 2023 were retrospectively included as the study objects.All patients were followed up for 1 year after surgery.Patients were divided into the shoulder joint function improvement group(n=415)and the shoulder joint function non-improvement group(n=36)according to scores of disabilities of the arm shoulder and hand(DASH).The preoperative MRI indicators and clinical indicators of the two groups were compared,and the risk factors of the outcome after ARCR in patients with FTRCT were analyzed by multivariate Logistic regression,and the receiver operating characteristic curve(ROC curve)was drawn.The predictive value of preoperative MRI indexes alone and in combination in patients with FTRCT undergoing ARCR was analyzed.Results 451 patients with FTRCT after ARCR were followed up for 1 year.The incidence of shoulder joint function non-improvement was 7.98％.Compared with the shoulder joint function improvement group,the shoulder joint function non-improvement group had longer preoperative tendon tear width and tendon retraction distance,higher degree of tendon degeneration,and shorter acromial humeral space(P＜0.05).Acromial humeral space ≤7.15 mm(OR=2.208,95％CI:1.255～3.883),tendon degeneration degree 2-3(OR=1.817,95％CI:1.066～3.096),tendon tear width＞2.16 cm(OR=2.246,95％CI:1.242～4.059)and tendon retraction distance＞2.10 cm(OR=2.186,95％CI:1.311～3.646)were risk factors for non-improvement of the shoulder joint in patients with FTRCT after ARCR(P＜0.05).Positive as shoulder joint function nonimprovement was included and negative as shoulder joint function improvement,ROC was drawn,and the predictive value of preoperative MRI indexes detection alone and combined in patients with FTRCT after ARCR was analyzed.The area under the curve(AUC)was 0.903,the sensitivity was 86.11％,and the specificity was 87.47％.Conclusion Patients with FTRCT who underwent ARCR surgery have better outcomes.Tendon tear width＞2.16 cm,tendon retraction distance＞2.10 cm,tendon degeneration degree of grade 2 to 3,acromial humeral space ≤7.15 mm are risk factors for poor outcomes,and the combined detection of preoperative MRI indexes has high predictive value.

Objective:To implement an overview of systematic reviews on the effects of brain-computer interface training on upper limb functional rehabilitation in stroke patients.Methods:The systematic review/Meta-analysis of the effect of brain-computer interface training on upper limb functional rehabilitation in stroke patients was electronically retrieved in PubMed, Web of Science, Cochrane Library, Embase, CINAHL, Embase, Joanna Briggs Institute Evidence-Based Health Care Center Database, China National Knowledge Infrastructure, Wanfang Data, VIP and China Biology Medicine disc. The search period was from database establishment to November 2024. Two researchers independently performed literature screening and data extraction and evaluated the quality of methodology, reporting, and evidence.Results:A total of 14 systematic reviews/Meta-analyses were included. The results showed that brain-computer interface training helped to improve upper limb motor function, muscle strength and activities of daily living in stroke patients, but the rehabilitative effect on muscle spasm needed to be further confirmed.Conclusions:Brain-computer interface training helps to improve upper limb motor function, muscle strength and activities of daily living in stroke patients. However, the methodological quality and reporting quality of the current studies are poor, and there is still a need for high-quality studies with rigorous design and standardized process to provide reference for clinical practice.