BACKGROUND:At present,domestic and foreign studies mainly focus on the comparison of different operation methods for intertrochanteric fracture of femur and the risk of failure in proximal femoral nail antirotation operation.There are few studies on the prognosis of hip function of affected limb after proximal femoral nail antirotation.OBJECTIVE:To analyze the influencing factors of poor hip function recovery in elderly patients with intertrochanteric fracture after proximal femoral nail antirotation surgery,and to construct a score system for predicting hip function after surgery and explore its value.METHODS:A total of 150 patients with intertrochanteric fracture of femur who received proximal femoral nail antirotation surgery in the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2023 were selected and divided into groups according to the Harris hip function score during postoperative follow-up.A score ≥80 was considered as the good group,and a score＜80 was considered as the poor group.Univariate and binary regression analyses were used to explore the risk factors leading to postoperative hip dysfunction.A score scale was established according to the risk factors.The value of this scoring system in predicting hip function after proximal femoral nail antirotation was investigated by using receiver operating characteristic curve.RESULTS AND CONCLUSION:(1)Among the 150 patients,according to the Harris score standard of the affected hip joint at 1 year follow-up,there were 52 cases in the group with poor functional recovery and 98 cases in the group with excellent functional recovery,with an unsatisfactory rate of 34.7％.(2)The results of univariate comparison between the two groups showed that there were significant differences in age,bone mineral density,number of preoperative underlying complications,type of lateral wall,position of spiral blade,quality of reduction and time of first exercise after surgery between the poor group and the good group(P＜0.05).(3)The results of binary Logistic regression analysis showed:Age ≥75 years old(OR=2.834),osteoporosis(OR=3.002),number of preoperative basic complications＞2(OR=4.024),lateral wall rupture(OR=2.999),position difference of spiral blade(OR=4.025),and time to exercise for the first time after surgery＞4 weeks(OR=3.153)were independent risk factors for hip dysfunction after proximal femoral nail antirotation for the intertrochanteric fractures(P＜0.05);poor reduction quality(OR=1.026)was not an independent risk factor(P＞0.05).(4)Based on the results of binary regression analysis,a score system for predicting good hip function after surgery was established.Receiver operating characteristic curve analysis showed that the threshold for predicting poor hip function after surgery was 4.5 points;the area under the curve was 0.797;the sensitivity was 83.7％and the specificity was 65.4％.(5)These results suggested that age ≥75 years old,osteoporosis,number of preoperative basic comorbidities＞2,lateral wall rupture,poor position of spiral blade,and first time out of bed exercise＞4 weeks after intertrochanteric fracture were risk factors for hip dysfunction after proximal femoral nail antirotation.The establishment of a score prediction system can provide reference value for early clinical identification of high-risk patients with postoperative hip dysfunction,and is conducive to guiding early clinical intervention,adopting more personalized treatment and rehabilitation programs,and promoting the recovery of hip function in patients after surgery.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective To explore the effects of the Otago Exercise Program(OEP)on activities of daily living,muscle strength,balance,and physical function in older adults with sarcopenia,to compare OEP with conventional exercise training,and to provide a basis for clinical rehabilitation programs for older adults with sarcopenia.Methods In this randomized controlled trial,120 older adults clinically diagnosed with sarcopenia were enrolled.The participants were randomly assigned to the OEP intervention group(experimental group)and the conventional exercise intervention group(control group),with 60 in each group.The experimental group underwent 12 weeks of OEP training,three times a week,with each session lasting 45 minutes.The control group underwent conventional exercise training following the same schedule.The Modified Barthel Index was used as the primary outcome measure to assess activities of daily living.Secondary outcome measures included muscle strength,gait stability,dynamic balance,and physical function status,evaluated using grip strength,6-meter walking speed,the Timed Up and Go Test(TUGT),and the Short Physical Performance Battery(SPPB).Results A total of 120 older adults with sarcopenia were included.The mean age of the participants was(80.17±8.48)years.Baseline data before treatment showed no statistically significant differences between the two groups.Both groups completed the treatment within 12 weeks without experiencing any adverse events.The baseline data for the experimental group were as follows,MBI at(67.00±22.76)points,hand grip strength at(15.29±4.94)kg,gait speed at(0.61±0.26)m/s,TUGT time at(15.05±6.74)s,and SPPB score at(6.17±1.40)points,while the corresponding post-intervention findings were as follows,(78.72±15.83)points,(17.67±5.83)kg,(0.77±0.28)m/s,(13.49±6.16)s,and(9.25±1.71)points,respectively.The experimental group showed improvements in all measures from baseline to post-intervention(P＜0.05 for all measures).As for the control group,the baseline data for the corresponding measures were as follows,(67.20±22.12)points,(15.00±5.35)kg,(0.58±0.23)m/s,(17.29±6.90)s,and(6.00±1.24)points,respectively.The post-intervention findings increased to(71.13±20.28)points,(15.47±5.72)kg,(0.64±0.28)m/s,(16.50±6.99)s,and(6.73±1.61)points,respectively,but the changes were not statistically significant(P＞0.05).Furthermore,an intergroup comparison of intervention effects(post-intervention minus preintervention)revealed significant differences in mean changes from baseline.The experimental group demonstrated improvements of(+11.72±6.32)points in modified Barthel Index,(+11.72±6.32)kg in grip strength,(+0.16±0.09)m/s in gait speed,(—1.56±1.32)s in TUGT time,and(—1.56±1.32)points in SPPB score.In contrast,the control group showed smaller changes of(+3.93±5.65)points,(+0.47±1.37)kg,(+0.06±0.07)m/s,(—0.79±1.54)s,and(+0.73±1.12)points,respectively(all P＜0.05).Intergroup comparisons revealed superior outcomes in the experimental group across all measures.Conclusion OEP significantly enhances activities of daily living,improves muscle strength,balance,and physical function in older adults,and is more effective than conventional rehabilitation exercise programs,making it suitable for extensive clinical application.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

Objective·To investigate the effects of liraglutide on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)and the underlying mechanisms.Methods·Twenty 8-week-old C57BL/6J mice were randomly divided into a normal chow diet group(Chow group)and a methionine-choline-deficient(MCD)diet group(MCD group),with 10 mice per group.The MCD diet was used to induce NAFLD.Each group was further divided into two subgroups,resulting in four subgroups:Chow+saline,Chow+liraglutide,MCD+saline,and MCD+liraglutide group.After daily intraperitoneal injection of liraglutide(400 μg/kg)or an equivalent volume of saline for 4 weeks,an intraperitoneal glucose tolerance test(IPGTT)was performed.Serum levels of aspartate transaminase(AST),alanine aminotransferase(ALT),total cholesterol(TC),triglyceride(TAG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured.Liver tissues were collected post-euthanasia to assess TAG content.Histopathological changes,lipid deposition,and fibrosis were evaluated via hematoxylin-eosin(HE)staining,Oil Red O staining,and Masson staining.Real-time quantitative PCR(qPCR)and Western blotting were used to analyze the expression of α-smooth muscle actin(α-SMA),fibronectin(FN),collagen type Ⅰ α(COL1A),matrix metalloproteinase 9(MMP9),tissue inhibitor of metalloproteinase 1(TIMP1),transforming growth factor β(TGF-β),SMAD3,and phosphorylated SMAD3(pSMAD3).Results·The IPGTT revealed that liraglutide intervention reduced blood glucose levels at 15,30,and 60 min,with a decreased area under the curve(AUC)(both P<0.05).Biochemical analysis showed that liraglutide lowered AST and ALT levels(both P<0.001),increased TC and HDL-C levels(both P<0.05),but had no significant effect on TAG or LDL-C in MCD mice.HE staining and Oil Red O staining revealed reduced lipid droplets,ballooning degeneration,and inflammatory infiltration in hepatocytes after liraglutide treatment.Masson staining indicated decreased collagen fiber deposition in the liver.qPCR and Western blotting analysis demonstrated upregulated expression of α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3,alongside downregulated MMP9 in MCD mice.Liraglutide reversed these changes,lowering α-SMA,FN,COL1A,TIMP1,TGF-β,and pSMAD3/SMAD3 expression while increasing MMP9 expression.Conclusion·Liraglutide ameliorates liver injury,lipid deposition,and fibrosis in NAFLD mice,through modulation of the TGF-β/SMAD3 pathway and regulating fibrosis-associated protein expression.

BACKGROUND:At present,domestic and foreign studies mainly focus on the comparison of different operation methods for intertrochanteric fracture of femur and the risk of failure in proximal femoral nail antirotation operation.There are few studies on the prognosis of hip function of affected limb after proximal femoral nail antirotation.OBJECTIVE:To analyze the influencing factors of poor hip function recovery in elderly patients with intertrochanteric fracture after proximal femoral nail antirotation surgery,and to construct a score system for predicting hip function after surgery and explore its value.METHODS:A total of 150 patients with intertrochanteric fracture of femur who received proximal femoral nail antirotation surgery in the Affiliated Hospital of Xuzhou Medical University from June 2021 to June 2023 were selected and divided into groups according to the Harris hip function score during postoperative follow-up.A score ≥80 was considered as the good group,and a score＜80 was considered as the poor group.Univariate and binary regression analyses were used to explore the risk factors leading to postoperative hip dysfunction.A score scale was established according to the risk factors.The value of this scoring system in predicting hip function after proximal femoral nail antirotation was investigated by using receiver operating characteristic curve.RESULTS AND CONCLUSION:(1)Among the 150 patients,according to the Harris score standard of the affected hip joint at 1 year follow-up,there were 52 cases in the group with poor functional recovery and 98 cases in the group with excellent functional recovery,with an unsatisfactory rate of 34.7％.(2)The results of univariate comparison between the two groups showed that there were significant differences in age,bone mineral density,number of preoperative underlying complications,type of lateral wall,position of spiral blade,quality of reduction and time of first exercise after surgery between the poor group and the good group(P＜0.05).(3)The results of binary Logistic regression analysis showed:Age ≥75 years old(OR=2.834),osteoporosis(OR=3.002),number of preoperative basic complications＞2(OR=4.024),lateral wall rupture(OR=2.999),position difference of spiral blade(OR=4.025),and time to exercise for the first time after surgery＞4 weeks(OR=3.153)were independent risk factors for hip dysfunction after proximal femoral nail antirotation for the intertrochanteric fractures(P＜0.05);poor reduction quality(OR=1.026)was not an independent risk factor(P＞0.05).(4)Based on the results of binary regression analysis,a score system for predicting good hip function after surgery was established.Receiver operating characteristic curve analysis showed that the threshold for predicting poor hip function after surgery was 4.5 points;the area under the curve was 0.797;the sensitivity was 83.7％and the specificity was 65.4％.(5)These results suggested that age ≥75 years old,osteoporosis,number of preoperative basic comorbidities＞2,lateral wall rupture,poor position of spiral blade,and first time out of bed exercise＞4 weeks after intertrochanteric fracture were risk factors for hip dysfunction after proximal femoral nail antirotation.The establishment of a score prediction system can provide reference value for early clinical identification of high-risk patients with postoperative hip dysfunction,and is conducive to guiding early clinical intervention,adopting more personalized treatment and rehabilitation programs,and promoting the recovery of hip function in patients after surgery.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.