Acute kidney injury (AKI) is one of the common critical illnesses characterized by a higher incidence, poor prognosis and limited effective therapeutics in clinical practice. Early diagnosis, etiologic differentiation and prognostic evaluation are crucial for improving outcomes and key components of integrated AKI management. However, the lack of ideal markers and intervention targets poses significant challenges in these aspects. Klotho, a protein predominantly synthesizes and secretes by renal tubular epithelial cells, has been shown to exert various protective effects on the kidney. Recent evidence suggests that abnormal Klotho levels are implicated in the pathogenesis and development of AKI, and hold promise for application in early diagnosis, etiologic recognition, and prognostic evaluation of AKI. Additionally, administration of exogenous Klotho protein or upregulation of endogenous Klotho expression has demonstrated preventive and therapeutic efficacy against AKI caused by a variety of etiologies. This paper reviewed the alterations in Klotho levels during AKI and evaluated its potential role in enhancing the integrated diagnosis and treatment of AKI.

A case of maxillary sinus cyst removal via lateral wall fenestration combined with sinus floor elevation and implant placement was reported.A 52-year-old female presented with bilateral posterior maxillary tooth loss.Preoperative CBCT revealed two dome-shaped pseudocysts at the right maxillary sinus floor,with intact sinus walls.During surgery,lateral wall fenestration was performed,followed by cyst aspiration and removal.The sinus mucosa was repaired using an absorbable collagen barrier membrane(Bio-Gide?),and deprotein-ized bovine bone matrix(Bio-Oss?)was implanted for bone augmentation.Postoperative CBCT at 9 months showed ideal bone height and density at the sinus floor,with no cyst recurrence and successful osseointegration of implants.The results suggest that concurrent cyst re-moval during sinus floor elevation could achieve stable bone augmentation when large cysts compromise the procedure.

Objective:To investigate the feasibility of transcatheter edge-to-edge repair (TEER) using a short-clip strategy for patients with moderate-to-severe or greater degenerative mitral regurgitation caused by commissural prolapse.Methods:This retrospective study included patients with severe mitral regurgitation secondary to commissural prolapse who underwent TEER at the Second Affiliated Hospital of Zhejiang University School of Medicine between September 2022 and July 2024. Preoperative clinical and imaging data, intraoperative details, procedural outcomes, and 1-month postoperative follow-up results were collected.Results:A total of 19 patients were enrolled, aged (74.1±6.1) years, including 12 males. Among them, 10 patients had external commissural prolapse, and 9 patients had internal commissural prolapse. Preoperatively, all patients exhibited severe mitral regurgitation (4+), with an effective regurgitant orifice area of (0.55±0.17) cm2, left atrial volume of (104.77±36.57) ml, left ventricular end-diastolic volume of (102.29±32.47) ml, left ventricular end-diastolic dimension of (5.34±0.59) mm, and prolapse width of (1.18±0.34) cm. All procedures utilized short clips (NTR or NTW clips) to target the prolapsed commissural region and were completed successfully without intraoperative complications. At 1-month follow-up, no mortality, stroke, single-leaflet device attachment, myocardial infarction, or unplanned mitral reintervention occurred. Mitral regurgitation severity improved to ≤2+ in all patients, with left atrial volume of (74.49±33.83) ml, left ventricular end-diastolic volume of (85.90±18.05) ml, and left ventricular end-diastolic dimension of (4.93±0.37) mm (all P<0.05). Conclusion:The short-clip strategy, focusing on precise clip placement at the commissural interface, is feasible and effective for TEER in patients with severe mitral regurgitation due to commissural prolapse.

A case of maxillary sinus cyst removal via lateral wall fenestration combined with sinus floor elevation and implant placement was reported.A 52-year-old female presented with bilateral posterior maxillary tooth loss.Preoperative CBCT revealed two dome-shaped pseudocysts at the right maxillary sinus floor,with intact sinus walls.During surgery,lateral wall fenestration was performed,followed by cyst aspiration and removal.The sinus mucosa was repaired using an absorbable collagen barrier membrane(Bio-Gide?),and deprotein-ized bovine bone matrix(Bio-Oss?)was implanted for bone augmentation.Postoperative CBCT at 9 months showed ideal bone height and density at the sinus floor,with no cyst recurrence and successful osseointegration of implants.The results suggest that concurrent cyst re-moval during sinus floor elevation could achieve stable bone augmentation when large cysts compromise the procedure.

Objective:To investigate the feasibility of transcatheter edge-to-edge repair (TEER) using a short-clip strategy for patients with moderate-to-severe or greater degenerative mitral regurgitation caused by commissural prolapse.Methods:This retrospective study included patients with severe mitral regurgitation secondary to commissural prolapse who underwent TEER at the Second Affiliated Hospital of Zhejiang University School of Medicine between September 2022 and July 2024. Preoperative clinical and imaging data, intraoperative details, procedural outcomes, and 1-month postoperative follow-up results were collected.Results:A total of 19 patients were enrolled, aged (74.1±6.1) years, including 12 males. Among them, 10 patients had external commissural prolapse, and 9 patients had internal commissural prolapse. Preoperatively, all patients exhibited severe mitral regurgitation (4+), with an effective regurgitant orifice area of (0.55±0.17) cm2, left atrial volume of (104.77±36.57) ml, left ventricular end-diastolic volume of (102.29±32.47) ml, left ventricular end-diastolic dimension of (5.34±0.59) mm, and prolapse width of (1.18±0.34) cm. All procedures utilized short clips (NTR or NTW clips) to target the prolapsed commissural region and were completed successfully without intraoperative complications. At 1-month follow-up, no mortality, stroke, single-leaflet device attachment, myocardial infarction, or unplanned mitral reintervention occurred. Mitral regurgitation severity improved to ≤2+ in all patients, with left atrial volume of (74.49±33.83) ml, left ventricular end-diastolic volume of (85.90±18.05) ml, and left ventricular end-diastolic dimension of (4.93±0.37) mm (all P<0.05). Conclusion:The short-clip strategy, focusing on precise clip placement at the commissural interface, is feasible and effective for TEER in patients with severe mitral regurgitation due to commissural prolapse.

Acute kidney injury (AKI) is one of the common critical illnesses characterized by a higher incidence, poor prognosis and limited effective therapeutics in clinical practice. Early diagnosis, etiologic differentiation and prognostic evaluation are crucial for improving outcomes and key components of integrated AKI management. However, the lack of ideal markers and intervention targets poses significant challenges in these aspects. Klotho, a protein predominantly synthesizes and secretes by renal tubular epithelial cells, has been shown to exert various protective effects on the kidney. Recent evidence suggests that abnormal Klotho levels are implicated in the pathogenesis and development of AKI, and hold promise for application in early diagnosis, etiologic recognition, and prognostic evaluation of AKI. Additionally, administration of exogenous Klotho protein or upregulation of endogenous Klotho expression has demonstrated preventive and therapeutic efficacy against AKI caused by a variety of etiologies. This paper reviewed the alterations in Klotho levels during AKI and evaluated its potential role in enhancing the integrated diagnosis and treatment of AKI.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

【Objective】 To investigate the prevalence and risk factors of primary nocturnal enuresis (PNE) in adolescents, and to explore its psychological effects. 【Methods】 During Sep.2020 and Dec.2020, an epidemiological survey was conducted among 6 408 junior and senior high school students in a region of Henan Province by stratified and cluster random sampling. The survey included general information questionnaire, urinary frequency, urgency, incontinence, recurrent urinary tract infection (RUTI), Enuresis Questionnaire, Self-esteem Scale (SES) and the Pittsburgh Sleep Quality Index (PSQI). 【Results】 A total of 7, 000 questionnaires were distributed and 6 408 (91.54%) were valid. The survey showed that the total prevalence of PNE among adolescents was 2.98%. The prevalence was 4.67% in those aged 12 years and 1.37% in those aged 18 years. The results of Logistic regression analysis showed that male (OR=1.677, P<0.05), overweight (OR=1.842, P<0.05), urgency (OR=1.676, P<0.05), frequency (OR=1.919, P<0.05), incontinence (OR=3.493, P<0.001), RUTI (OR=2.535, P<0.001) and family history (OR=3.005, P<0.001) were related to the risk of PNE. The SES score of PNE patients was lower than that of non-PNE group (z=-3.097, P<0.05), and the PSQI was higher (z=-5.456, P<0.05). 【Conclusion】 The prevalence of PNE is high in adolescents and decreases gradually with age. Male, overweight, frequency, urgency, incontinence, RUTI and family history are risk factors. PNE has a negative impact on self-esteem and sleep quality in adolescents.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone