OBJECTIVE To evaluate the cost-utility of benmelstobart combined with anlotinib and chemotherapy as first-line treatment for extensive-stage small cell lung cancer （ES-SCLC） from the perspective of China’s healthcare system. METHODS Based on the data from the ETER 701 study， a partitioned survival model was constructed with a cycle of 3 weeks to simulate the total cost， quality-adjusted life years （QALY）， and incremental cost-effectiveness ratio （ICER） over 10 years for patients with ES- SCLC treated with benmelstobart plus anlotinib and chemotherapy， or chemotherapy alone. One-way sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the simulation results. The willingness-to-pay （WTP） threshold was set at 3 times the per capita gross domestic product （GDP） of China in 2023， which amounted to 268 074 yuan/QALY. RESULTS Compared with chemotherapy alone， benmelstobart combined with anlotinib and chemotherapy gained 0.438 QALY more at the cost of 403 505.55 yuan more， with an ICER of 922 031.37 yuan/QALY， which was higher than the WTP threshold set in this study. One-way sensitivity analysis showed that benmelstobart’s cost and utility value of the progression-free survival state had a greater impact on the ICER value； probabilistic sensitivity analysis confirmed the robustness of the model； only when the price of benmelstobart was reduced by 75.4%， the combined regimen would be cost-effective. CONCLUSIONS The first-line treatment of ES-SCLC with benmelstobart combined with anlotinib and chemotherapy is not cost-effective from the perspective of China’s healthcare system at present.

OBJECTIVE To evaluate the efficacy， safety and economics of calcium channel modulators in the treatment of diabetic peripheral neuropathic pain （DPNP）， and provide evidence-based evidence for clinical drug selection and decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang data， VIP net， CBM and official websites of foreign health technology assessment （HTA） institutions were systematically searched to collect HTA reports， systematic review/meta-analyses， and pharmacoeconomic studies of pregabalin， gabapentin， crisugabalin， and mirogabalin for the treatment of DPNP. The timeframe for all searches was from the inception to June 2024. After data extraction and quality assessment， the results of the included studies were analyzed descriptively. RESULTS A total of 16 articles were included， involving 1 HTA report， 7 systematic reviews/meta- analyses， and 8 pharmacoeconomic studies. No studies on crisugabalin were retrieved. Compared with placebo， both pregabalin and mirogabalin reduced end point pain scores and increased the proportion of patients with ≥30% and/or ≥50% reduction in pain scores. Pregabalin also improved patient global impression of change （PGIC）. Gabapentin was similar to placebo in reducing end point pain scores and increasing the proportion of patients with ≥30% and/or ≥50% reduction in pain scores， but gabapentin improved PGIC of patients. Compared with pregabalin， mirogabalin was more effective in the treatment of pain. The safety of pregabalin and mirogabalin was similar， and compared with placebo， both pregabalin and mirogabalin increased the risk of common adverse reactions such as dizziness and somnolence. The safety of gabapentin was similar to placebo and duloxetine. Compared with duloxetine， pregabalin and gabapentin were not cost-effective. Compared with gabapentin， pregabalin was cost-effective. Mirogabalin was cost-effective， as compared with placebo and pregabalin. CONCLUSIONS Pregabalin and mirogabalin are effective in the treatment of DPNP， the efficacy of mirogabalin is better than pregabalin， and the safety is similar between them. The economic conclusions vary from country to country， pending a pharmacoeconomic study based on our population.

OBJECTIVE To evaluate the cost-effectiveness of capecitabine metronomic chemotherapy combined with aromatase inhibitor （AI） versus AI monotherapy as first-line treatment for hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， thereby providing evidence-based support for clinical therapeutic decision- making and healthcare policy formulation. METHODS Based on the MECCA trial， a partitioned survival model was constructed using a 4-week cycle length to simulate outcomes over patients’ lifetime. The model outputs included total costs， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Sensitivity analyses were performed to validate the robustness of base-case results， while scenario analyses examined the cost-effectiveness of both treatment strategies under 10-year， 20-year， and lifetime time horizons. RESULTS With the willingness-to-pay （WTP） threshold set at 1 times China’s 2024 per capita gross domestic product （GDP） （95 749 yuan/QALY）， patients receiving capecitabine metronomic chemotherapy combined with AI regimen gained incremental utility （0.66 QALYs） while incurring higher costs， with ICER of 27 684.85 yuan/QALY. Results of the one-way sensitivity analysis showed that factors with significant impacts on ICER included the cost discount rate， drug costs of the capecitabine metronomic chemotherapy combined with AI group， utility value in the progression-free survival state， follow-up costs， and treatment costs in the subsequent stablephase. Probabilistic sensitivity analysis indicated that when the WTP threshold ≥49 250 yuan/QALY， the capecitabine metronomic chemotherapy combined with AI regimen had a 100% probability of being cost-effective. Scenario analysis results demonstrated that capecitabine metronomic chemotherapy combined with AI regimen was more cost-effective than the AI alone regimen across 10-year， 20-year， and lifetime study horizons. CONCLUSIONS Under the premise that the WTP threshold is set at 1 times China’s per capita GDP in 2024， capecitabine metronomic chemotherapy combined with AI regimen is more cost-effective than the AI alone regimen as the first-line treatment for HR+/HER2－ metastatic breast cancer.

OBJECTIVE To evaluate the cost-effectiveness of sacituzumab tirumotecan （ST） versus chemotherapy treatment physician’s choice （TPC） as second-line and later-line treatment for metastatic triple-negative breast cancer （mTNBC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was constructed based on the OptiTROP-Breast 01 trial， with a cycle length of 4 weeks and a time horizon of 10 years， applying a 5% discount rate. Quality adjusted life year （QALY） and costs were used as outcome measures， and the incremental cost-effectiveness ratio （ICER） of ST versus TPC for second-line and later-line treatment of mTNBC was calculated. Sensitivity analyses were conducted to validate the robustness of the base-case results. RESULTS At a willingness-to-pay threshold （WTP） of 3 times China’s 2024 per capita gross domestic product （GDP） （287 247 yuan/QALY）， patients receiving ST gained incremental utility （0.42 QALY） at a higher cost， yielding an ICER of 205 562.07 yuan/QALY， which was lower than WTP， indicating that ST was more cost-effective compared to TPC. One-way sensitivity analysis revealed that key factors influencing the ICER included the utility value of progression-free survival and the price of ST. Probabilistic sensitivity analysis and scenario analysis showed that the base-case results were robust. CONCLUSIONS From the perspective of China’s healthcare system， at a WTP of 3 times China’s per capita GDP， ST is more cost-effective than TPC as second-line and later-line treatment for mTNBC.

OBJECTIVE: To compare clinical efficacy of transaxillary posterior margin approach and translateral margin approach for the treatment of Miller typeⅡand Ⅳ scapular fractures. METHODS: From June 2020 to June 2024, 28 patients with fresh scapular fractures (Miller typeⅡand Ⅳ) who were treated with open reduction and locked plate internal fixation were retrospectively analyzed and divided into two groups. There were 13 patients in posterior axillary margin group, including 8 males and 5 females, aged from 26 to 71 years old with an average of (39.2±6.5) years old;5 patients with typeⅡand 8 patients with type Ⅳ according to Miller classification;9 patients caused by falling down, 4 patients caused by car accident;7 patients on the right side, 6 patients on the left side;the time from injury to operation ranged from 3 to 5 days with an average of (4.07±0.86) days. There were 15 patients in lateral scapula margin group, including 10 males and 5 females, aged from 27 to 63 years old with an average of (43.6±8.5) years old;7 patients with typeⅡand 8 patients with type Ⅳ according to Miller classification;10 patients caused by falling down, 5 patients caused by car accident;6 patients on the right side, 9 patients on the left side;the time from injury to operation ranged from 3 to 5 days with an average of (4.20±0.67) days. Operative time, intraoperative blood loss, fracture healing time, glenopolar angle (GPA) immediately after operation were compared between two groups. Visual analogue scale (VAS) and Constant-Murley shoulder joint function score were used to evaluate clinical effect at 3 and 6 months after operation, respectively, and the joint motions were evaluated at 6 months after operation. RESULTS: None of patients occurred wound infection, vascular and nerve damage, loosening or rupture of internal fixation. Both groups were followed up for 8 to 12 months with an average of (9.6±1.5) months. Operative time and intraoperative blood loss of posterior axillary margin group were (76.92±5.60) min and (84.86±10.08) ml, respectively, which were better than those of lateral scapula margin group(84.67±6.93) min and(115.00±12.39) ml(P<0.05). Immediate GPA in posterior axillary margin group (36.62±0.87) °and lateral scapula margin group (36.20±0.82)°were significantly improved compared with preoperative (16.10±1.14) °, (16.20±1.20) °(P<0.05), while there was no statistical significance between two groups (P>0.05). There were no significant difference in fracture healing time and postoperative VAS at 3 and 6 months between two groups (P>0.05). Postoperative Constant-Murley score of posterior axillary margin group (75.00±4.02) was higher than that of lateral scapular margin group (70.86±4.24) at 3 months (P<0.05), while there was no significant difference between two groups at 6 months after operation (P>0.05). At 6 months after operation, joint motion of posterior axillary margin group in flexion (160.38±13.61)°, abduction (154.61±13.91)°, rotation (83.08±2.53)°, rotation (62.69±2.59) ° and extension (51.54±3.15) °, respectively, which were higher than that of lateral scapular margin group in (148.00±15.44)°, (144.00±11.05)°, (79.67±3.99)°, (57.33±4.95)°, (47.33±4.16)°(P<0.05). CONCLUSION Compared with lateral margin of scapula intermuscular space approach, Buttress approach through the posterior axillary margin for the treatment of Miller typeⅡand Ⅳ scapular fractures provides extensive intraoperative visual field exposure, stable fracture support and less surgical trauma, which could shorten operative time and reduce intraoperative blood loss, providing a new reference for the treatment of complex scapular fractures.
Humans ; Male ; Female ; Middle Aged ; Scapula/surgery* ; Adult ; Aged ; Fractures, Bone/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Axilla/surgery*

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections

The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
Testosterone/metabolism* ; Humans ; Male ; Circadian Clocks/genetics* ; Circadian Rhythm Signaling Peptides and Proteins/metabolism* ; Circadian Rhythm/physiology* ; Hypogonadism/metabolism* ; Erectile Dysfunction/metabolism* ; Infertility, Male/metabolism* ; Prostatic Neoplasms/metabolism* ; Men's Health

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome