OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard of care （SoC） in the treatment of heart failure with mildly reduced ejection fraction （HFmrEF） or preserved ejection fraction （HFpEF）. METHODS Based on a phase Ⅲ clinical trial， a Markov model was constructed from the perspective of China’s healthcare system to compare the treatment outcomes of finerenone combined with SoC regimen versus SoC regimen alone in the treatment of different cardiac functional statuses of HFmrEF/HFpEF. Using quality-adjusted life year （QALY） as the health output index， 3 times China’s per capita GDP in 2023 as the willingness-to-pay （WTP） threshold， a simulation was conducted with a 3-month cycle length and a 10- year time horizon， incorporating an annual discount rate of 5%. The dynamic changes across various stages of HFmrEF/HFpEF treated with finerenone combined with SoC versus SoC alone were simulated to evaluate the long-term effectiveness and costs of the two treatment strategies. Additionally， one-way sensitivity analysis and probabilistic sensitivity analysis were performed， to test the robustness of the results. RESULTS The incremental cost-effectiveness ratio （ICER） of the finerenone combined with SoC regimen versus SoC regimen alone was 179 504.75 yuan/QALY， which was below the WTP threshold set in this study， indicating that the finerenone combined with SoC regimen possessed certain economic advantages. The results of one-way sensitivity analysis showed that the utility value of NYHA Ⅱ status， the drug price of finerenone， the discount rate， and the probability of hospital transfer for both groups had a great influence on ICER， but did not affect the robustness of the model. The probabilistic sensitivity analysis also confirmed the robustness of the model. CONCLUSIONS Under the WTP threshold set in this study， finerenone combined with SoC is cost-effective in the treatment of HFmrEF/HFpEF， compared with the SoC regimen.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.

Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.

Objective:To investigate the risk factors for unsatisfactory early pain relief after percutaneous vertebroplasty (PVP).Methods:This was a retrospective cohort study, included 208 patients with osteoporotic vertebral compression fracture admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to March 2020. According to the early pain relief after PVP, they were divided into good pain relief group ( n=188) and poor pain relief group ( n=20). Influence factors were record and compare, including the gender, age, preoperative lumbar bone density, body mass index, number of fractured vertebral bodies, degree of fracture compression, operation time, bone cement leakage, bone cement dispersion, thoracolumbar fascia injury, sarcopenia, and Hospital Anxiety and Depression Scale (HADS) score and visual analogue score of pain between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and independent samples t-test was used for comparison between groups; the Chi-square was used for comparison of count data between groups. Univariate and multivariate Logistic regression analysis were used to investigate the independent risk factors for poor early pain relief after PVP. Results:All patients underwent surgery successfully, without serious complications such as cement embolism, cardio-cerebrovascular accident, epidural hematoma, spinal cord and nerve injury. There were no significant differences in operation time, bone cement leakage and bone cement diffusion between the two groups ( P>0.05). The statistical results showed that compared with the good pain relief group, the patients with poor pain relief group had lower preoperative lumbar bone density ( t=2.35, P=0.020), higher proportion of thoracolumbar fascial injury ( χ2=8.66, P=0.003) and sarcopenia( χ2=7.15, P=0.007), higher preoperative HADS score ( t=2.51, P=0.013). Univariate and multivariate Logistic regression analysis showed that lower preoperative bone density, higher preoperative HADS score, and higher proportion of thoracolumbar fascia injury and sarcopenia were independent influencing factors for poor early pain relief after PVP. Conclusions:The poor early pain relief after PVP is associated with lower preoperative lumbar bone density, preoperative complications such as thoracolumbar fascial injury, sarcopenia, and preoperative anxiety. Effective prevention of the above factors should be taken during the perioperative period to avoid serious complications.

Objective:To explore interspinous fusion capacity after interspinous distraction fusion (ISDF) device implantation, a preliminary biomechanical analysis and histological evaluation were performed.Methods:The experimental animals were procured from the Science and Research Laboratory Animal Center of Beijing Friendship Hospital, Capital Medical University. The animals were 8-9 weeks old and with an average weight of 25 kg. 15 mini-pigs were randomly divided into three groups, the sham operation group, the decompression group and the ISDF fixed decompression group, 5 animals per group. The sham operation group was treated with simple incision and exposed lamina suture. The decompression group received unilateral decompression and the ISDF fixed decompression group experienced unilateral hemilaminectomy decompression and ISDF fixation. The graft-bed site was filled with purified bone graft material without any autograft bone. After 6 months feeding, all experimental animals were sacrificed and the corresponding lumbar vertebrae was obtained. The samples were fixed on the spinal test system and the range of motion of flexion-extension, lateral bending and rotation were tested through a multiaxial robotic system. The ISDF device samples were embedded for hard tissue sections and stained with hematoxylin-eosin and toluidine blue to assess new bone formation. Normally distributed measurement data were expressed as mean±standard deviation( ± s), and independent samples t-test were used for comparisons between groups. Results:In comparison to the sham operation group, the decompression group exhibited a statistically significant increase in intervertebral mobility, with an average of 61.6% in anterior flexion, 44.7% in posterior extension, 65.0% in left lateral flexion, 49.6% in right lateral flexion, 83.8% in left rotation, and 64.2% in right rotation ( P<0.05). In comparison to the decompression group, the ISDF fixed decompression group exhibited a statistically significant decrease in intervertebral mobility, with an average of 40.0% in anterior flexion, 21.3% in posterior extension, 31.7% in left lateral flexion, 22.3% in right lateral flexion, 28.7% in left rotation, and 35.3% in right rotation ( P<0.05). Well-defined bone tissue can be observed in the histological images of ISDF fixed decompression group samples after 6 months. In the histological part, toluidine blue staining showed extensive new bone formation. The hyperchromatic osteoblasts cells and density bone tissue can be observed in hematoxylin-eosin staining slides. Conclusions:The implantation of ISDF provide the necessary stabilization for promoting fusion. The osteogenesis that occurs within graft-bed site of the ISDF device offers the possibility of interspinous fusion.

Objective To analyze the application characteristics of acupuncture and moxibustion in the treatment of postherpetic neuralgia(PHN)using complex networks;To provide clinical acupuncture and moxibustion treatment with application basis for acupoint selection,acupuncture and moxibustion,and treatment ideas.Methods The clinical research literature on acupuncture and moxibustion treatment for PHN was retrieved from CNKI,Wanfang Data,VIP,PubMed and Web of Science.The literature was screened according to the inclusion and exclusion criteria,and Excel 2019 was used to establish an acupuncture and moxibustion treatment PHN database.SPSS Modeler 18.0 software was used for modeling and association rule analysis,and Gephi 0.10.1 software was used for complex network analysis.Results Totally 237 articles were included,and 262 acupuncture and moxibustion prescriptions data were extracted,involving a total of 115 acupoints,with a total use frequency of 1 432 times.The top 10 most frequently used acupoints were Ashi acupoint(214 times)and Jiaji acupoint(198 times),Zusanli(74 times),Taichong(74 times),Sanyinjiao(66 times),Hegu(65 times),Yanglingquan(62 times),Xuehai(60 times),Zhigou(53 times),and Quchi(52 times).The association rule analysis showed that the acupoint combination with the highest correlation was Ashi acupoint-Jiaji acupoint.K-core hierarchical analysis and community analysis on the complex network of the acupoint prescriptions obtained two core acupoint groups.Therapy analysis showed that filiform needle acupuncture was the most commonly used intervention for acupuncture treatment of PHN;syndrome type-acupoint analysis showed that the syndrome types with the highest frequency of PHN were liver meridian heat stagnation,blood stasis and collaterals obstruction,and spleen meridian damp-heat;tonic and diarrhea-acupoint analysis showed that the main operating techniques were neutral-tonifying and neutral-discharging.Conclusion Acupuncture and moxibustion treatment for PHN mainly selects local acupoints,Ashi acupoint and Jiaji acupoint are often selected,and focusing on the cooperation with distal acupoints.The external and internal meridians are mostly selected according to different syndrome types.The operation is performed using neutral-tonifying and neutral-discharging techniques.Commonly used filiform acupuncture combined with electro-acupuncture,pricking,cupping and other therapies.The application characteristics can provide clinical reference for the treatment of PHN.

Objective To investigate the effects of Gonglaomu external lotion on wound healing, sinus depth and pituitary prolactin (PRL) in patients with non-lactating mastitis (NMP) in the late stage of ulceration. Methods A total of 140 patients with NMP in the late stage of ulceration were selected and divided into observation group (n=70) and control group (n=70). Image J software was used to calculate the wound area before and after treatment, and the amount of exudation was recorded; the sinus depth was measured with silver probe before and after treatment; the level of PRL was detected by chemiluminescence before and after treatment; the efficacy, wound area, exudate volume, sinus depth and PRL level were compared between the two groups. Results The total effective rate of the observation group was higher than that of the control group; after treatment, the wound area and exudation volume of the observation group were lower than those of the control group; after treatment, the sinus depth in the observation group was lower than that in the control group; the PRL in both groups decreased after treatment, and the PRL of the observation group was lower than that of the control group; the recurrence rate in the observation group was lower than that in the control group; all the between-group differences mentioned above were statistically significant (P < 0.05). Conclusion Gonglaomu external lotion can effectively improve condition of wound healing, sinus depth and PRL level in patients with NMP in the late stage of ulceration.

Objective:To analyze the clinical efficacy of inter-spinal distraction fusion and fixation and Posterior lumbar interbody fusion in the treatment of lumbar disc herniation with stenosis, and to evaluate the health economics of the two surgical methods.Methods:Retrospectivly analyzed the clinical data of 400 patients with lumbar disc herniation with stenosis, who were enrolled in Beijing Friendship Hospital, Capital Medical University from Jan. 2015 to Jan. 2019, including 190 male cases and 210 female cases, aged from 50 to 87 years old, with the average age of 67.97. All patients were divided into two groups according to different surgical methods. Among them, 200 patients used interspinous process fusion and distraction fixation (ISDFF group), the other 200 cases used posterior lumbar decompression and pedicle internal fixation (PLIF group). All patients completed the follow-up time of more than 1 year after operation. The basic information of patients′ age, gender, total number of days in hospital, intraoperative bleeding, operation time, surgical incision length and other basic information were observed. The Oswestry dysfunction index (ODI), the Japanese Orthopaedic Association Score (JOA) and the visual analog scale (VAS) were used to evaluate the relief of symptoms before and after the two groups of patients. Total medical expenses, anesthesia expenses, surgical expenses and other expenses were analysed. The software of SPSS 20.0 were conducted to analyze data.Results:The patients in the ISDFF group were (70.84±8.93) years old, and the PLIF group was (65.10±10.23) years old ( t=5.98, P=0.008). The operation time in the ISDFF group was (59.21±16.22) min, and the operation time in the PLIF group was (81.31±17.24) min( t=13.20, P<0.001). The bleeding volume of the ISDFF group was (33.24±11.31) mL, and the bleeding volume of the PLIF group was (67.30±17.61) mL ( t=23.02, P<0.001). The length of the surgical incision in the ISDFF group was (8.27±2.53) cm, and the length of the surgical incision in the PLIF group was (11.15±1.91) cm ( t=11.848, P<0.001). The total hospitalization time in the ISDFF group was (15.15±0.54) days, and the total hospitalization time in the PLIF group was (19.86±0.97) days( t=4.26, P<0.001). There was no significant difference in preoperative ODI, JOA and VAS between the two groups ( P>0.05). Symptoms of postoperative patients were significantly improved compared with preoperative. There were statistical differences in ODI, JOA and VAS between the two groups before and after operation ( P<0.05). However, ODI, JOA and VAS were no statistical difference between the two groups after operation. Complications occurred in 5 cases of the two groups of patients, including two cases of superficial infection in the PLIF group, two cases of dural tear in the PLIF group, one case of spinous process fracture in the ISDFF group. The total hospitalization fee for ISDFF was (57 450±8 670) (yuan), and the total hospitalization fee for PLIF was (75 770±1 640) (yuan), with statistical differences ( t=9.92, P<0.001). The cost of ISDFF operation was 1864±38.19 (yuan), and the cost of PLIF operation was 2352±41.39 (yuan) ( t=8.65, P<0.001). ISDFF antibacterial drug usage fee was 635.5±64.69 (yuan), PLIF antibacterial drug usage fee was 1449±307.1 (yuan) ( t=2.59, P<0.001). The one-time medical material cost during the ISDFF operation was (38 990±300) (yuan), and the one-time medical material cost during the PLIF operation was (52 110±150) (yuan) ( t=5.88, P<0.001). The excellent and good rate of ISDFF group was 92%, and that of PLIF group was 86%. In this study, the total cost of hospitalization was used as an indicator to measure the cost, and further cost-effectiveness evaluation was made. For every good patient, the cost of the ISDFF group was 62 450 yuan, and the cost of the PLIF group was 88, 100 yuan. Conclusions:ISDFF is beneficial to reduce the cost of medical insurance in China, which is in line with the direction of national reform to reduce medical expenditure. It is a surgical method worthy of wide promotion and has a good application prospect.