Neurodegenerative diseases constitute a group of chronic disorders characterized by the progressive loss of neurons. Major neurodegenerative conditions include Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis. Pathologically, these diseases are marked by the accumulation of aggregates formed by pathological proteins such as amyloid-β, tau, α-synuclein, and TAR DNA-binding protein 43. These proteins assemble into amyloid fibrils that undergo prion-like propagation and dissemination, ultimately inducing neurodegeneration. Understanding the biology of these protein aggregates is fundamental to elucidating the pathophysiology of neurodegenerative disorders. In this review, we summarize the molecular mechanisms underlying the aggregation and transmission of pathological proteins, the processes through which these protein aggregates trigger neurodegeneration, and the interactions between different pathological proteins. We also provide an overview of the current diagnostic approaches and therapeutic strategies targeting pathological protein aggregates.
Humans ; Neurodegenerative Diseases/metabolism* ; alpha-Synuclein/metabolism* ; Amyloid beta-Peptides/metabolism* ; tau Proteins/metabolism* ; Protein Aggregation, Pathological/metabolism* ; DNA-Binding Proteins/metabolism* ; Animals ; Protein Aggregates/physiology*

Objective:To evaluate the clinical efficacy of infraorbital rim drilling midface lift combined with composite lower blepharoplasty.Methods:Retrospective analysis of clinical data from the patients who underwent combined midface lift and lower blepharoplasty at Department of Medical Cosmetic Center, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medical, between January 2022 and February 2024.The infraorbital rim drilling midface lift combined with lower blepharoplasty was performed via a subciliary incision approach. Through a subciliary incision, the herniated orbital fat was excised, followed by fixation of the orbital septum to the infraorbital rim periosteum. Drill holes were created at the medial and lateral infraorbital rim, and arcuate suspension of the midface was performed using 2-0 absorbable sutures (SXPP1A405). Postoperative follow-up assessed midface lifting outcomes and complication rates. The wrinkle severity rating scale (WSRS) was used to grade nasolabial folds pre- and postoperatively (5-point scale: higher scores indicating more pronounced folds). Patient-reported outcomes were assessed using the Face-Q questionnaire, evaluating: (1) overall facial satisfaction, (2) satisfaction with surgical results, and (3) satisfaction with decision (scale 0-100; higher scores indicating greater satisfaction/less decisional regret). Descriptive statistical methods were employed for data analysis.Results:A total of 43 patients were enrolled, comprising 7 males and 36 females, with a mean age of (50.6±12.2) years (range: 32-73 years). Postoperative follow-up averaged (11.9±4.6)months. All patients demonstrated significant improvement in lower eyelid bags, tear trough deformity, midface elevation, and nasolabial folds. Surgical complications included: residual lower eyelid fat ( n=5), intermittent fixation point pain persisting >1 month ( n=4), mild residual tear trough deformity ( n=4), and hematoma ( n=1). Nasolabial fold WSRS scores decreased from ( 3.7±0.9 ) points to(2.9±0.6)points following surgery. In 38 patients, Face-Q scores demonstrated high satisfaction levels: appearance-related satisfaction scored (80.9 ± 10.3)points and satisfaction with decision scored (82.4 ± 8.9)points, indicating favorable patient-reported outcomes. Conclusion:The infraorbital rim drilling-assisted midface lift combined with comprehensive lower blepharoplasty effectively corrects midface ptosis while addressing lower eyelid bags. This technique provides reliable fixation points through drilling, resulting in stable and long-lasting lifting outcomes with high patient satisfaction.

The current transformation of the tripartite linkage of medical treatment has gradually shifted towards collaborative development and governance among medical care,medical insurance,and medicine,necessitating a clear understanding of the internal mechanisms underpinning this collaboration and governance to lay a theoretical foundation for practical exploration.Drawing on synergetics theory,it delves into the self-organizing characteristics of the collaborative development and governance among the tripartite system,grasping its fundamental operational laws.Through a questionnaire survey of the main functional departments in each field of the tripartite system to verify the rationality of the sequence parameters selected for the study.It ultimately identifies the order parameters as the value standard centered on health,the interest contract focused on public interest,new system for mobilizing resources nationwide,the innovative capacity of the pharmaceutical industry,and the rigorous accountability system.Furthermore,it systematically expounds on the self-organizing evolution process of the collaborative development and governance among the tripartite system,thereby revealing the inherent mechanisms of its collaborative development and governance.It proposes countermeasures and suggestions for establishing and improving diversified collaboration mechanisms,innovating monitoring and early warning mechanisms,and fostering positive feedback mechanisms,aiming to facilitate more scientific and efficient collaborative development and governance among the tripartite system.

Objective:To compare the efficacy and safety of a domestic hair follicle extraction system versus traditional follicular unit excision (FUE) in extracting hair follicles for the treatment of androgenetic alopecia (AGA) .Methods:A multicenter, randomized, self-controlled clinical trial was conducted on AGA patients aged 18 - 59 years who were recruited from the Huashan Hospital, Fudan University, the Affiliated Hangzhou First People's Hospital, and the China-Japan Friendship Hospital between June 2023 and September 2024. Each patient's scalp was randomly divided into two sides (experimental side vs. control side) using an envelope method. The experimental side underwent robotic hair transplantation with a domestic hair follicle extraction system, and the control side underwent traditional FUE. Hair follicles were extracted from the safe donor area in the occipital region, and implanted into the ipsilateral hair loss area. The primary outcome was the hair transection rate which was calculated immediately after follicular extraction. The secondary outcomes included the hair follicle unit loss rate and the change in hair density at the recipient site on postoperative day 14. Safety was evaluated by assessing the incidence of folliculitis at the donor site on postoperative day 14 and the overall incidence of adverse events. Surgical outcomes were evaluated at 9 months after surgery. Comparisons of evaluation indicators among groups were performed by using a paired t test or Wilcoxon signed-rank test. Results:A total of 55 patients with AGA (51 males and 4 females, aged 32.71 ± 5.75 years) completed the hair follicle transplantation and postoperative follow-up. The hair transection rate ( M[ Q1, Q3]) was 6.65% (4.56%, 10.16%) in the experimental group and 5.28% (3.04%, 8.89%) in the control group (difference = 1.24%, 95% CI: -0.24%, 2.65%) . The hair follicle unit loss rate was 2.00% (1.00%, 3.50%) in the experimental group and 0.50% (0, 2.00%) in the control group, with a significant difference between the two groups ( P = 0.008) . On postoperative day 14, there was no significant difference in the hair density between the experimental group and control group (72.20 ± 25.95 per cm 2vs. 76.49 ± 30.84 per cm 2, P = 0.173) . At 9-month follow-up, both groups showed improvement in the investigator's overall score in the recipient areas. Seven adverse events occurred in 7 subjects (12.72%) in each group, and all were mild folliculitis. Conclusion:The domestic hair follicle extraction system demonstrated comparable efficacy and safety to the traditional FUE in hair transplantation.

Objective:We aimed to analyze the spatio-temporal trend of breast cancer incidence and mortality in Shandong Province from 2012 to 2023 and predict the development trend from 2024 to 2030.Methods:Data on the incidence and mortality of breast cancer in Shandong Province from 2012 to 2023 were obtained from the Shandong Cancer Registry. The incidence, age-specific incidence, mortality, and age-specific mortality in different years, as well as in urban and rural areas, were calculated, and the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) rate was calculated using Joinpoint 4.8.0.1 software. The global and local spatial autocorrelation analysis were performed using GeoDa 1.12 software. The Bayesian age-period-cohort model was used to predict the trend of breast cancer incidence and mortality from 2024 to 2030.Results:From 2012 to 2023, the breast cancer age-standardized incidence rate (ASIR) showed an increasing trend. The ASIR increased from 30.48/100 000 in 2012 to 39.94/100 000 in 2023 (AAPC=2.59%, P<0.001). The ASIR of urban and rural females also showed an upward trend. Additionally, the ASIR in rural areas (AAPC=3.33%, P<0.001) increased more than that in urban areas (AAPC=1.83%, P=0.002). The incidence peak of breast cancer mainly concentrated in population aged 45-64 years, and with the increase of years, the incidence peak gradually moved forward. The age-standardized mortality rate (ASMR) showed a downward trend. The ASMR decreased from 6.89/100 000 in 2012 to 4.93/100 000 in 2023 (AAPC=-3.12%, P<0.001). The ASMR of urban and rural females also showed a downward trend (urban: AAPC=-3.56%, P=0.007; rural: AAPC=-2.72%, P<0.001). The spatial analysis showed that from 2015 to 2023, the clustering areas of breast cancer incidence and mortality in Shandong had changed significantly. In 2015, the "High-high clusters" of ASIR mainly included Wendeng District in Weihai City, Dongying District, Kenli District, Lijin County, Guangrao County in Dongying City, Tianqiao District, Shizhong District in Jinan City; In 2023, the "High-high clusters" mainly included Jiaxiang County, Liangshan County, Jinxiang County, Wenshang County, Rencheng District in Jining City, Hedong District in Linyi City, Guangrao County in Dongying City. In 2015, the "High-high clusters" of ASMR only included Wenshang County in Jining City. In 2023, the "High-high clusters" mainly included Laizhou County in Yantai City, Junan County and Yishui County in Linyi City, Gaotang County in Liaocheng City, Dongping County and Ningyang County in Taian City. The Bayesian age-period-cohort model predicted that the ASIR trend of breast cancer in Shandong tended to be smooth (AAPC=0.33%, P=0.001). However, the ASMR remained decreasing (AAPC=-4.68%, P<0.001). Conclusions:The breast cancer incidence in Shandong showed an increasing trend, and it is expected to be smooth by 2030. However, the mortality showed a continuous downward trend. The incidence peak was mainly in the population aged 45-64 years, with obvious regional differences. Targeted prevention and control measures should be taken for high-risk groups and areas in Shandong Province.

Objective:To evaluate the effect of esketamine on the quality of postoperative sleep in preschool children undergoing day surgery.Methods:This was a prospective randomized controlled study. One hundred and four preschool children of either sex, aged 4-7 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, underwent elective day surgery for strabismus correction under general anesthesia at the First Affiliated Hospital of Zhengzhou University from July to September 2024, were selected. The preschool children were divided into 2 groups ( n=52 each) by the random number table method: control group (group C) and esketamine group (group S). In group S, additional esketamine 0.25 mg/kg was intravenously injected during anesthesia induction. The sleep quality scores were evaluated using the Children′s Sleep Habit Questionnaire by the guardians on the night before surgery, the 1st night after surgery, the 3rd night after surgery and the 7th night after surgery, and development of postoperative sleep disorders (the Children′s Sleep Habit Questionnaire score >41) was recorded. The FLACC pain scores and usage rate of flurbiprofen axetil were recorded immediately before leaving the postanesthesia care unit (PACU) and on days 1, 3 and 7 after surgery. The time of laryngeal mask airway removal, length of stay in PACU and development of adverse reactions such as increased oral secretions, agitation, nausea and delirium within 48 h after surgery were recorded. Results:Compared with group C, the Children′s Sleep Habits Questionnaire score and incidence of postopoerative sleep disorders were significantly decreased on the 1st night after surgery, the FLACC pain scores were decreased immediately before discharge from the PACU and at 1 day after surgery, the usage rate of flurbiprofen axetil was decreased ( P<0.05), and no significant change was found in the time of laryngeal mask airway removal, length of stay in PACU and incidence of postoperative adverse reactions in group S ( P>0.05). Conclusions:Anesthesia induction with esketamine 0.25 mg/kg can improve the quality of postoperative sleep in preschool children undergoing day surgery.

Objective:To investigate the status and diagnostic reference levels (DRLs) of adult CT radiation dose based on survey result from some hospitals in Beijing.Methods:From September to December 2023, the survey results for 50 hospitals were collected in Beijing, including 47 tertiary hospitals and 3 second grade general hospitals. The CT data sets in total of 20 items including head (sequential scanning), head (spiral scanning), head perfusion, sinus, neck, chest, chest (low dose scanning), abdomen, pelvis, abdomen-pelvis, chest-abdomen-pelvis, lumbar spine, CT urography, coronary CTA (retrospective), coronary CTA (prospective), head CTA, neck CTA, aorta CTA, leg CTA and knee were collected on clinical commonly used CT scanners with annual qualified state inspection. For each item, radiation dose data was collected continuously and randomly for up to 50 cases for every CT scanner. Using the volume CT dose index (CTDI vol) and dose length product (DLP) as dose parameters, the median value of each item in each hospital was obtained. The median CTDI vol and DLP values of all hospitals were arranged, and the local DRL of each item was set as the 75th percentile of the median values. The obtained DRLs were compared with the DRLs issued by domestic and international radiological protection organizations. Results:A total of 26 031 dose values of adult patients were collected and 25 996 dose values were left while 35 invalid values removed.For different CT users, CTDl vol, DLP and scanning phases were different for the same item. The five items with the highest CTDI were head perfusion, head sequential scanning, head spiral scanning, coronary CTA (retrospective mode), and sinus. The five items with the highest DLP were CTU, head perfusion, leg CTA, chest-abdomen-pelvis and aortic CTA. The CTDI vol of CTU was only 16.9 mGy (75th percentile), while the DLP was as high as 2 394.9 mGy·cm (75th percentile). The survey showed that the DRLs of most items in Beijing was lower than the national DRLs of domestic and foreign standards, and the DRLs of a small number of items were slightly higher. Conclusion:The current CT dose level in Beijing is not consistent with national DRLs released at home and abroad, so it is necessary to establish local DRLs according to the clinical status in Beijing.

Objective:To investigate devices for radiodiagnosis used in medical institutions in Beijing, China, as well as radiation workers and the devices′ application frequencies, in order to provide data support for determining radiation protection measures and allocating resources for clinical radiodiagnosis.Methods:In October 2023, questionnaires were distributed to the members of the Radiation Technology Branch of the Beijing Medical Association who work in medical institutions at different levels across varying districts of Beijing. The collected data included information about devices for radiodiagnosis and radiation workers, as well as the application frequencies of various medical X-ray imaging devices during 2018-2022, in 38 medical institutions of Level 3 Grade A, Level 3, and Level 2 in 14 municipal districts of Beijing. Then, the collected data were organized using the Microsoft Power BI software to form report models, followed by the statistical analysis of data on the devices, radiation workers, and application frequencies were using the RStudio software.Results:The 38 medical institutions in Beijing possess 591 devices for radiodiagnosis and 2 018 staff in the departments of radiology, including 1 037 radiologic technologists and 738 physicians, with 1.77 technologists and 1.26 physicians arranged for a single device on average. From 2018 to 2022, among all examinations of radiodiagnosis, computed tomography (CT) scans showed the highest frequencies, with total and average annual growth rates of 138.06% and 108.40%, respectively. Specifically, chest CT scans exhibited total and average annual growth rates of 225.20% and 122.50%, respectively. X-ray imaging ranked second in application frequency, with total average annual growth rates of 70.20% and 91.53%, respectively. Notably, chest X-ray imaging showed total and average annual growth rates of 63.89% and 89.41%, respectively.Conclusions:From 2018 to 2022, X-ray imaging examinations displayed significantly fluctuating frequencies with an overall decline trend in the 38 medical institutions. In contrast, the CT scans showed increased frequencies, with chest CT scans displaying an increased frequency and proportion. This necessitates ensuring the justification of CT scans.

Objective:To investigate the efficacy and safety of transurethral incision for the treatment of ureterocele in infants.Methods:A retrospective analysis of 28 cases of ureterocele admitted from March 2012 to May 2023 were reviewed, all of which were less than 1 year old, 16 male and 12 female, with an average age of(5.7±3.5)months. The ureterocele was located on the left side in 8 cases, on the right side in 15 cases, and bilaterally in 5 cases. There were 12 cases of single system ureterocele, of which 7 cases were unilateral and 5 cases were bilateral. Duplex system ureterocele was observed in 16 cases, all of which were unilateral. Clinical manifestations: urinary tract infection in 13 cases, 11 cases of ureterocele or hydronephrosis and ureteral dilation were found during antenatal examination, and 4 cases of ureterocele were found after birth. Urological ultrasound, intravenous pyelography(IVP) and voiding cystourethrography(VCUG) were performed in all children, and 17 cases underwent magnetic resonance urolography (MRU), and confirm the diagnosis of ureterocele preoperatively. All of the cases were performed the transurethral incision.The ureterocele was punctured and incised 1-2 mm at the base of the bulge, and 2-4 points were punctured according to the bulge atrophy. Bilateral ureteroceles were punctured and incised simultaneously. Postoperative urine routine test, urinary tract color ultrasound and VCUG were performed to determine if there is urinary tract infection, hydronephrosis, ureteral dilation and bulging, and whether a second surgery is needed.Results:All operations were conducted successfully. The intraoperative bleeding was less than 3 ml and no intraoperative complications. The operative time was (28.4±10.3) min. The median postoperative follow-up was 34 (32, 36) months. Six cases underwent postoperative VCUG examination. Eleven children were recovered well with single systemic ureterocele. One child developed grade Ⅳ vesicoureteral reflux(VUR)and combined with bladder diverticulum, and ureterocele underwent open diverticulotomy and ureteral reimplantation six months after surgery. Nine children were recovered well with duplex systemic ureterocele. Six cases of children developed infection, of which 2 cases had an infection once within one month after TUI, and the other four cases still had intermittent infections after six months and VCUG was performed, and one case showed grade Ⅲ VUR of the lower ureter, which was observed conservatively, while the other three cases had enlarged cysts but no VUR, and upper heminephrectomy was performed, and the patients recovered well after surgery. Except for these 6 exceptions, in another case, after ten years of follow-up, the ureterocele became larger but no VUR, and the results were good after a second transurethral incision. There was no significant difference in the postoperative infections, new VUR cases, and secondary surgeries between the two groups.Conclusions:Transurethral incision has good surgical effect on children with single system ureterocele and duplex system ureterocele, and has advantages of easy operation, less trauma, safety and effectiveness, and few complications. It deserves to be recommended as the treatment of choice, especially for infants and young children.

Objective:To investigate the efficacy and safety of darolutamide in the treatment of patients with metastatic hormone-sensitive prostate cancer.Methods:A retrospective analysis was conducted on 17 cases of prostate cancer patients who received treatment with darolutamide in combination with ADT at our hospital from January to December 2022. The median age was 70 (range: 56 to 92) years old. The median pre-treatment prostate-specific antigen (PSA) level was 63.50 (range: 29.16 to 700.74) ng/ml. Sixteen cases had a Gleason score of 8 or above, and 11 cases were classified as high tumor burden (with four or more bone metastases and/or visceral metastases). The patients were treated with darolutamide in combination with goserelin (10.8 mg, subcutaneous injection, every 12 weeks). The decrease in PSA levels was observed at 2 weeks and at 1, 2, 3, and 6 months post-treatment. The time to achieve a 50% decrease in PSA level (PSA50), a 90% decrease (PSA90), and a PSA level of ≤0.2 ng/ml was recorded.Adverse drug reactions were also documented.Results:All the 17 patients were followed up and continued to receive darolutamide at our center without any loss to follow-up. The median follow-up time was 11.4(8.9, 15.3)months. It showed a median PSA decrease from baseline of 83.33% at 2 weeks, 95.37% at 1 month, 96.71% at 2 months, 97.22% at 3 months, and 99.10% at 6 months. The median time to achieve PSA50, PSA90, and PSA ≤ 0.2 ng/ml were 1.3 (0.9, 1.7)months, 1.7 (1.2, 2.4)months, and 3.6 (2.9, 4.5)months respectively. Six patients with bone metastases experienced relief of metastatic lesions after treatment. Only one patient developed papules on the left upper limb, which were assessed as grade 1 rash, and the rash disappeared after three days treatment of topical application of hydrocortisone cream.Conclusions:Darolutamide could rapidly control and significantly reduce PSA levels in prostate cancer patients, with a favorable safety profile.