OBJECTIVE To provide a basis for aligning Chinese pharmacoeconomic research on heart failure （HF） with international standards. METHODS A qualitative comparison o f domestic and global HF pharmacoeconomic studies was conducted across four dimensions： research methods and model application， research perspectives and endpoints， data sources and parameter selection， and policy translation and practical impact. RESULTS & CONCLUSIONS Global studies predominantly utilize long-term dynamic models， societal perspectives， real-world data integration， and directly inform reimbursement decisions. Conversely， domestic research often relies on short-term simplified models， a single healthcare system perspectives， literature-derived data， and individual medicine recommendations. Future domestic studies should transition to long-term dynamic modeling， develop localized disease-specific utility databases via big data， establish reimbursement-linked closed-loop mechanisms， and foster multidisciplinary collaboration to optimize healthcare resource allocation.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

Objective To analyze the fluid resistance characteristics of different drafting formations in marathon swimming using computational fluid dynamics(CFD)method,and provide theoretical guidance for selecting optimal drafting strategies in competitions and training.Methods Multi-swimmer models were established via three-dimensional body scanning technology,and various formation models(I-,A-,V-,L-,H-type)were created by adjusting lateral and longitudinal distances between swimmers.The ANSYS Discovery Live software was used to simulate the overall resistance of different models and the resistance of individual swimmers within formations.Results The I3-type formation exhibited an overall drag reduction effect,reducing total resistance by 55.21％,whereas other formations increased overall resistance.The V-type formation showed the most significant resistance increase(31.88％).During drafting,the lowest resistance position was the rear position in the I3-type formation,while the highest resistance position was the middle position in the L-type formation.When leading,the fluid resistance of the leading swimmer in the A-type formation was significantly greater than that of an individual swimmer(P＜0.05).Conclusions Longitudinal drafting formations demonstrated superior drag reduction effects,with the rear position in a three-person longitudinal arrangement showing the optimal drag reduction.Considering both tactical considerations and drag reduction effects,swimmers are advised to avoid the middle position in lateral formations.

Over 2 million thoracoscopic pulmonary resections are performed globally each year,however,postoperative persistent air leak(PAL)remains a common and challenging complication.It not only prolongs hospital stays and increases treatment costs but may also lead to severe complica-tions,particularly inducing a higher risk in patients undergoing mechanical ventilation.In recent years,with the improvement of preoperative preventive measures,the advancement of surgical tech-niques,and the application of repair materials,the incidence of PAL has decreased.This review sys-tematically summarized the definition,clinical impact,risk factors and preventive strategies of PAL,and explored commonly used treatment modalities,such as thoracic drain management,pleurodesis and the application of novel repair materials.It also analyzed the effectiveness,safety and challenges of existing techniques.Furthermore,this review proposed the establishment of an enhanced recovery after surgery(ERAS)integrated pathway combining bovine pericardium(BP)patch with electro-me-chanical stapler and conducted corresponding treatment benefit-cost assessment.

Objective To analyze the fluid resistance characteristics of different drafting formations in marathon swimming using computational fluid dynamics(CFD)method,and provide theoretical guidance for selecting optimal drafting strategies in competitions and training.Methods Multi-swimmer models were established via three-dimensional body scanning technology,and various formation models(I-,A-,V-,L-,H-type)were created by adjusting lateral and longitudinal distances between swimmers.The ANSYS Discovery Live software was used to simulate the overall resistance of different models and the resistance of individual swimmers within formations.Results The I3-type formation exhibited an overall drag reduction effect,reducing total resistance by 55.21％,whereas other formations increased overall resistance.The V-type formation showed the most significant resistance increase(31.88％).During drafting,the lowest resistance position was the rear position in the I3-type formation,while the highest resistance position was the middle position in the L-type formation.When leading,the fluid resistance of the leading swimmer in the A-type formation was significantly greater than that of an individual swimmer(P＜0.05).Conclusions Longitudinal drafting formations demonstrated superior drag reduction effects,with the rear position in a three-person longitudinal arrangement showing the optimal drag reduction.Considering both tactical considerations and drag reduction effects,swimmers are advised to avoid the middle position in lateral formations.

Objective:To investigate the clinical effects of free posterior interosseous artery perforator flap on reconstruction of the soft tissue defects of multiple fingers in one hand.Methods:Clinical data of 9 patients with soft tissue defect of multiple fingers in one hand admitted to the Department of Hand Surgery, Yongkang Orthopedic Hospital between January 2021 and August 2023 were retrospectively studied. The patients were 7 males and 2 females, aged between 19 and 55 years old. The soft tissue defects of 2 patients with 3 fingers injury and 7 patients with 2 fingers injury were reconstructed with free posterior interosseous artery perforator flaps. The size of defects in single finger was 1.5 cm×2.5 cm-3.0 cm×4.5 cm. The size of flap was 2.5 cm×7.0 cm-3.5 cm×13.0 cm. The posterior cutaneous nerve of the forearm were sutured to the intrinsic nerve of palmar side of the 14 fingers. Donor sites in forearm were directly sutured. After discharge, regular follow-up at outpatient clinic and through WeChat interviews were conducted to observe the appearance and texture of the flaps, finger fullness, donor site function and appearance, as well as patient satisfaction. For the flaps with anastomosis of cutaneous nerve, the recovery of TPD of the flap was tested. Sensory recovery was assessed according to the British Medical Research Council (BMRC) sensory function assessment criteria. Hand functions were evaluated using the Total Active Movement (TAM) of fingers of the Hand Surgery of the Chinese Medical Association.Results:All of the 20 flaps survived and were evaluated through follow-up visits, which ranged from 6 to 25 months with an average of 13 months. The flaps were soft, unbloated and without obvious pigmentation. The protective sensations were recovered with an average static TPD of 14 flaps anastomosed with cutaneous nerve was of 9.7 (7-13) mm. Among them, S 3+ 10 fingers, S 3 4 fingers; 6 fingers of flap without sutured cutaneous nerve, S 2 5 fingers, S 1 1 finger. According to the TAM of Hand Surgery of Chinese Medical Association, the results were excellent for 15 fingers and good for 5 fingers. There was no scar contracture in the forearm donor sites and motor function was not affected. Conclusion:Posterior interosseous artery perforator flap has the advantages of thin flap, similar texture to the hand, good recovery in sensory, and minimal damage to the donor site. Therefore, it is a good option in reconstruction of soft tissue defects of multiple fingers in one hand.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

Objective:This study aims to investigate the determinants influencing the efficacy of microsurgical sperm retrieval in individuals diagnosed with idiopathic non-obstructive azoospermia (iNOA).Methods:A retrospective analysis was performed on the clinical data of 757 patients diagnosed with iNOA who underwent microsurgical sperm extraction at Peking University Third Hospital between January 2019 and December 2021. The median age of patients was 31(29, 33)years, and the duration of infertility was 3(2, 5)years. A total of 169 patients (22.3%) received preoperative pharmacological treatment with agents such as follicle-stimulating hormone, human chorionic gonadotropin, or aromatase inhibitors. Additionally, 327 patients (43.2%) underwent testicular biopsy (TESA) prior to surgery. Among these, 51 cases (15.9%) exhibited sperm presence on smear microscopy, while 57 cases (17.8%) demonstrated sperm presence on pathological examination. The pathological classifications of the biopsies included 102 cases (31.9%) of reduced spermatogenic function, 66 cases (20.6%) of delayed sperm maturation, and 63 cases (19.7%) of sertoli cell-only syndrome.Preoperative median pituitary prolactin(PRL)was 9.1(6.5, 12.5)ng/ml, follicle-stimulating hormone (FSH)20.1(14.2, 28.5)U/L, luteinizing hormone (LH)7.9(5.5, 11.3)U/L, testosterone(T)117 .0(81.3, 154.0)nmol/L, estradiol(E2)8.7(6.3, 11.8)pmol/L. Under general anesthesia, patients underwent microsurgical testicular incision for sperm retrieval.The surgical testicular volume was measured at a median of 6(5, 10) ml. Among the cases studied, 59 patients (7.7%) underwent left testicular surgery, 213 patients (28.1%) underwent right testicular surgery, and 485 patients (64.0%) underwent bilateral testicular surgery. Furthermore, 44 patients (5.8%) underwent a second microsurgical sperm retrieval procedure, while 4 patients (0.5%) underwent a third procedure.Based on the presence of sperm identified during the surgical procedure, participants were categorized into a sperm retrieval group and a non-sperm retrieval group. Clinical data of these two groups were analyzed. A subgroup analysis was performed on the observed indicators. Both univariate and multivariate logistic regression analyses were employed to examine the factors influencing the micro sperm retrieval rate.Results:Among the 757 iNOA patients, 255(33.7%) obtained sperm through micro sperm retrieval, while 502(66.3%) did not obtain sperm through micro sperm retrieval. The age of sperm-receiving group was higher than that of the non-sperm-receiving group [32(30, 35)years vs. 30(28, 33)years, P<0.01], and the course of infertility was longer than that of the non-sperm-receiving group [3.0(2.0, 5.5)years vs. 3.0(2.0, 4.0)years, P=0.004]. There was no significant difference in the sperm acquisition rate in the subgroup with or without preoperative drug treatment [38.5%(65/169)vs. 32.7%(185/566), P=0.164]. There was statistical significance in the sperm collection rate of different TESA results in subgroups [85.7%(24/28)of sperm were detected by microscopic smear and pathological examination and 75.9%(22/29)of sperm were detected by pathological examination and no sperm were detected by microscopic smear and 17% of sperm were not detected by microscopic smear and pathological examination (42/247), P<0.01). The rate of spermatogenesis in the subgroup with low spermatogenic function was significantly higher than that in the subgroup with spermatogenic maturation retardation and sercell-only syndrome [47.1%(48/112), 12.1%(8/66)vs. 11.1%(7/63), P<0.01]. There was no significant difference in testicular volume between the seminal and non-seminal groups [6.0(5.0, 10.0)ml vs. 6.0(5.0, 9.5)ml, P=0.862]. Pituitary prolactin [8.3(5.8, 12.0)ng/ml vs. 9.3(7.5, 13.0)ng/ml, P=0.001] and FSH[18.3(11.8, 27.4)U/L vs. 20.7(15.2, 28.7)U/L, P=0.005] in spermated group were lower than those in non-spermated group. Luteinizing hormone [7.6(5.1, 11.0)U/L vs. 8.0(5.6, 11.5)U/L, P=0.126], testosterone [8.8(6.0, 11.8)nmol/L vs. 8.7(6.4, 11.7)nmol/L, P=0.607], estradiol [124.0(87.8, 156.0)nmol/L vs. 114.5(79.9, 151.3)nmol/L, P=0.105] had no significant difference. The recovery rate of the first operation was higher than that of the second operation [97.7%(43/44)vs. 81.8%(36/42), P=0.032]. The sperm retrieval rate of bilateral operation was significantly lower than that of unilateral operation [6.0% bilateral (29/485)vs. 86.4% left (51/59)vs. 82.2% right (175/213), P<0.01]. The proportion of no sperm on one side of bilateral operation and only 4.7%(23/485)on the opposite side were obtained. The results of multivariate analysis showed that >30 and ≤40 years old subgroup ( OR=2.226, 95% CI 1.364-3.632, P=0.001), >40 and ≤50 years old subgroup ( OR=4.282, 95% CI 1.457-12.588, P=0.008)was higher than that of >20 and ≤30 years old subgroup. The sperm acquisition rate of the sperm subgroup was significantly increased by smear microscopy and pathological examination ( OR=6.486, 95% Cl 1.444-29.127, P=0.015), while the sperm acquisition rate of the sperm subgroup was not significantly decreased by smear microscopy and pathological examination ( OR=0.420, 95% Cl 0.200-0.881, P=0.022). The pathological type of puncture was associated with lower spermatogenesis maturation block ( OR=0.099, 95% CI 0.019-0.509, P=0.006). Higher FSH (>7.6 U/L)was associated with lower sperm yield ( OR=0.324, 95% CI 0.122-0.856, P=0.023). Conclusions:Age, FSH level, results of testicular biopsy and pathologic type of biopsy are independent factors affecting the sperm retrieval rate of iNOA patients undergoing micro-TESE. The success rate of sperm retrieval diminished following multiple surgical procedures. Furthermore, for patients who did not have sperm successfully retrieved from one side, that the likelihood of sperm retrieval from contralateral surgery would also be low.

【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.