Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective To investigate the changing trends in etiology and treatment of male urethral stricture in recent 10 years.Methods A total of 940 male patients with urethral stricture admitted to the Department of Urology of Beijing Jishuitan Hospital during Jan.2013 and Dec.2022 were continually collected.The clinical data were divided into two groups according to the time of admission,namely the group from 2013 to 2017 and the group from 2018 to 2022,for a comparative analysis of the previous and subsequent 5 years.The etiology,location,length and the type of treatment of urethral stricture were retrospectively analyzed.Results The causes of the 940 cases of male urethral stricture were trauma in 447(47.55％),iatrogenic injury in 220(23.40％),idiopathic causes in 128(13.62％),lichen sclerosus(LS)in 78(8.30％),infection in 46(4.89％),and other causes in 21(2.23％).The treatment methods were urethroplasty in 691(73.51％),direct vision internal urethrotomy(DVIU)in 122(12.98％),urethral dilatation in 86(9.15％),and suprapubic cystostomy in 41(4.36％).Compared with the previous 5 years,in the past 5 years,the proportion of urethral stricture caused by trauma decreased significantly(60.34％vs.41.71％,P＜0.001),while the proportion of iatrogenic injury increased significantly(17.63％vs.26.05％,P=0.005).In the past 5 years,the proportion of urethroplasty increased from 68.81％to 75.66％(P=0.027),while the proportion of DVIU decreased from 19.66％to 9.92％(P＜0.001).Inthe past 5 years,the proportion of membranous urethral stenosis decreased significantly(26.98％vs.50.85％,x2=51.06,P＜0.001),the proportion of penile urethral stricture(21.40％vs.7.80％,=26.37,P＜0.001)and meatal stenosis(9.30％vs.4.75％,x2=5.80,P＜0.001)increased significantly.Conclusion In the past decade,trauma was the main cause of male urethral strictures,but its proportion showed a decreasing trend.Iatrogenic injury led to a gradual increase in urethral strictures,which was the second leading cause of male urethral stricture.The application of urethroplasty increased significantly,making it the main treatment method for male urethral stricture.

Objective:To investigate the application value of biological muscle flap in laparo-scopic radical proximal gastrectomy with esophagogastric anastomosis.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 10 patients with adeno-carcinoma of esophagogastric junction who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from May 2023 to August 2023 were collected. All patients were males, aged (65±5)years. All patients underwent laparoscopic radical proximal gastrectomy and esophagogastric anastomosis with digestive tract reconstruction using the esophagogastric biological muscle flap. Observation indicators: (1) surgical situations and early complications; (2) follow-up and late com-plications. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations and early complications. All 10 patients success-fully completed the surgery without conversion to open surgery, and the operation time was (166±18)minutes. Cases with digestive tract reconstruction as end-to-side anastomosis and Overlap anas-tomosis were 1 and 9, respectively. The time of digestive tract reconstruction, the number of lymph node dissected, volume of intraoperative blood loss, time to postoperative first anal exhaust, time to postoperative first intake of liquid food, duration of postoperative hospital stay were (40±12)minutes, 24±6, (41±9)mL, (3.4±0.5)days, (4.1±1.0)days, (8.3±0.7)days in the 10 patients. Of 4 cases with postoperative early complications, 1 case developed pulmonary infection (Clavien-Dindo grade Ⅱ) on the second day after surgery, with pulmonary infection absorbed after 5 days of antibiotic treat-ment. Two cases experienced chest distress and shortness of breath on the third day after surgery, with the diagnosis of a small to moderate amount of pleural effusion after chest B-ultrasound examination. After pleural puncture and active treatment, the symptoms of them were improved and the pleural effusion disappeared. There was 1 case with choking sensation when eating solid food, which was started from the third week after surgery. Upper gastrointestinal imaging revealed mild anastomotic stenosis of Clavien-Dindo grade Ⅰ in the patient, who was improved after conservative treatment. On the 7th day after surgery, all 10 patients underwent upper gastrointestinal angiography, and no anastomotic leakage or stenosis occurred. There was no sign of contrast agent reflux in the supine position and 30° head down position. (2) Follow-up and late complications. All 10 patients were followed up for 59.5(range, 31.0-127.0)days. The esophageal reflux scale score of 10 patients was 1.4±0.3. During the follow-up, 1 case underwent gastroscopy on 40 days after surgery, which showed reflux esophagitis with Los Angeles grade as B and the Clavien-Dindo grade as Ⅰ. There was no clinical symptom such as heartburn or acid reflux. Results of 24-hour pH monitoring showed that the patient experienced 24 instances of reflux in an upright position and 15 instances of reflux in a supine position, with no prolonged reflux. The total reflux time within 24 hours was 75 minutes. The DeMeester score was 38.3. Results of esophageal pressure measurement showed that the esophageal contraction morphology was normal, but the anastomotic opening was not well relaxed. The rest of 9 cases had no complication such as reflux esophagitis.Conclusion:Biological muscle flap applied in the laparoscopic radical proximal gastrectomy with esophagogastric anastomosis is safe and feasible, with satisfied short-term efficacy.

Objective To investigate the effect of the monoamine oxidase A(MAOA),Maoa c.1409 T＞C synonymous mutation on anxiety,fear,and other emotional behaviors in mice.Methods In this study,CRISPR/Cas9 technology was used to construct a mouse model of a single nucleotide polymorphism(SNP)synonymous mutation.We evaluated the differential effect of this gene between males and females through animal behavior and gene expression studies in animal models.In terms of animal behavior,an open field test,elevated plus maze test,defensive burial experiment,forced swimming test,and 3D behavioral analysis were used.Other method were used to evaluate behavioral differences between male and female mice with polymorphisms in Maoa synonymous mutant genes.Results The result of the open field experiment showed that the residence time of female SNP mice in the central area was significantly higher than that of male SNP mice(P＜0.001).In the elevated cross maze experiment,the EPM result showed that the time and frequency of male SNP mice entering the open arm were higher than those of female SNP mice,but there was no significant difference.The defensive burial test showed that the number and duration of excavations by female SNP mice in response to rat urine were significantly reduced(P＜0.01).The FST showed that SNP females had shorter immobility time and longer swimming time(P＜0.05),and thus their depression was lower than males.3D-AI fine behavior analysis showed no significant male and female differences,except for the movement trajectory and climbing behavior of mice.The MAOA enzyme content of female SNP mice was significantly lower than that of male SNP mice(P＜0.001),but there was no significant difference in enzyme activity between male and female SNP mice.Conclusions The synonymous mutation of Maoa c.1409 T＞C acts by affecting the expression of MAOA and may have different fear,anxiety,and mood effects in male and female SNP mice.

OBJECTIVE: To evaluate the surgical methods for treating distal urethral stricture. METHODS: The clinical data of 80 patients with distal urethral stricture in Beijing Jishuitan Hospital, Captial Medical University between January 2018 and December 2022 were retrospectively collected. Including male genital lichen sclerosus (MGLS) 33 cases, iatrogenic injury 25 cases, postoperative hypospadias 12 cases, and other causes such as trauma 10 cases. Among these cases, strictures involved the urethral meatus in 54 instances, of which 38 were treated with meatotomy (MO), 7 with penile skin flap urethroplasty (PSFU), and 9 with oral mucosa graft urethroplasty (OMGU). There were also 26 instances where strictures involved both the navicular fossa and meatus; one case underwent PSFU while 25 underwent OMGU. Based on different surgical methods used for treatment purposes we divided the patients into MO group, PSFU group and OMGU group. The age of the three groups was (48.8±20.0) years, (53.3±21.8) years and (44.5±16.4) years. The mean±SD body mass index (BMI) was (28.6±3.9) kg/m², (29.6±3.2) kg/m² and (29.2±4.8) kg/m². The preoperative maximum flow rate was (5.8±2.3) mL/s, (6.8±2.4) mL/s and (5.7±3.1) mL/s. RESULTS: All the operations were successfully completed without Clavien Ⅲ or Ⅳ complications. The median length of strictures (measured intraoperatively) in the three groups were 1.1 (1.0, 1.6), 1.5 (1.1, 2.0) and 4.0 (2.5, 5.0) cm. The median operation time was 60.0 (60.0, 75.0), 85.0 (75.0, 112.5) and 180.0 (75.0, 330.0) min. The median estimated blood loss was 5.0 (2.0, 10.0), 15.0 (5.0, 42.5) and 180.0 (135.0, 216.3) mL. The median postoperative hospital stay was 3.5 (2.0, 5.0), 6.5 (3.5, 7.0) and 7.5 (7.0, 11.3) days. The median follow-up duration was 40.0 (26.3, 57.3), 55.0 (18.8, 62.8) and 52.5 (30.5, 64.0) months. The median postoperative maximum flow rate was 18.3 (15.5, 19.8), 19.2 (16.1, 20.1) and 17.2 (14.2, 19.6) mL/s. Among the 38 patients with MO, 33 cases had normal urination without reintervention, and 5 cases experienced recurrent strictures and required regular urethral dilation. Among the 8 patients with PSFU, 7 cases had normal urination without reintervention, and one case developed a urinary fistula, for which intervention was recommended but the patient opted to maintain the status quo. Among the 34 patients with OMGU, 28 cases had normal urination without reintervention. There were 6 instances of stenosis recurrence, with 5 cases requiring regular urethral dilations and one case requiring reconstructive surgery. The overall success rate of operation was 85.0%, and the reintervention rate was 15.0%. Statistical analysis revealed significant differences in etiologies among the three groups (P=0.002), as well as in stricture locations (P < 0.001), length of strictures (P < 0.001), operation time (P < 0.001), estimated blood loss (P < 0.001) and postoperative hospital stays (P < 0.001). However, no significant differences were observed in terms of age, BMI, history of previous urethral stricture surgeries, preoperative maximum flow rate, follow-up duration, postoperative maximum flow rate and reintervention rate. Univariate and multivariate Logistic regression analyses indicated that a history of previous urethral stricture surgeries was a risk factor for postoperative reintervention (P=0.026). CONCLUSION MO and PSFU are primarily suitable for treating short-segment (≤1.5 cm) distal penile urethral strictures, whereas OMGU is more appropriate for longer segment strictures. MO and OMGU can both be utilized in managing MGLS cases. PSFU and OMGU are more conducive to improving the appearance of the urethral meatus. The success rate of surgical management of distal penile urethral stricture is 85.0%, 15.0% of the patients still require surgical intervention after surgery, and having history of previous urethral stricture surgeries is a risk factor for postoperative reintervention.
Humans ; Urethral Stricture/surgery* ; Male ; Retrospective Studies ; Middle Aged ; Adult ; Urethra/surgery* ; Surgical Flaps ; Penis/surgery* ; Mouth Mucosa ; Urologic Surgical Procedures, Male/methods* ; Plastic Surgery Procedures/methods* ; Lichen Sclerosus et Atrophicus/surgery* ; Operative Time ; Skin Transplantation/methods* ; Aged

Accurate classification of the acetabular injuries and appropriate treatment plan are great challenges for orthopedic surgeons because of the irregular anatomical structure of the acetabulum and aggregation of important vessels and nerves around it. Letournel-Judet classification system has been widely applied to classify acetabular fractures. However, there are several limitations, including incomplete inclusion of fracture types, difficulty in understanding and insufficient guidance for surgical treatment, etc. Serious complications such as traumatic arthritis are common due to wrong classification and diagnosis and improper selection of surgical strategy, which brings a heavy burden to the society and families. Three-column classification, based on anatomic characteristics, has advantages of containing more fracture types and being easy to understand, etc. To solve the problems existing in the diagnosis and treatment process based on Letournel-Judet classification, achieve accurate diagnosis and treatment of patients with acetabular fractures, and obtain satisfactory prognosis, the Orthopedic Trauma Emergency Center of Third Hospital of Hebei Medical University and the Trauma Orthopedic Branch of the Chinese Orthopedic Association organized experts from relevant fields to formulate the Expert consensus on the accurate diagnosis and treatment of acetabular fractures based on three-column classification ( version 2023) in terms of principles of evidence-based medicine. Based on the three-column classification, 15 recommendations were proposed, covering the diagnosis, treatment, complication prevention and management, etc, so as to provide reference for accurate diagnosis and treatment of acetabular fractures.

Objective:To explore the clinical outcome of early endoscopic realignment with flexible cystoscope for pelvic fracture urethral injury.Methods:We retrospectively collected and analyzed the clinical data of patients with pelvic fracture urethral injuries in ER of Beijing Jishuitan Hospital from March 2018 to June 2022.Seventy-six male patients with PFUI were reviewed and 60 patients were included due to the integrity of data collected. The patients were divided into early endoscopic realignment (EER) group and suprapubic cystostomy (SC) group according to the acute management. There were 33 patients and 27 patients in EER group and SC group, respectively. The age of the patients were (42.2±13.8)years and (44.1±15.0) years in EER group and SC group, respectively. The causes of the injuries were car accident, falling and crush, the percentage of the patients were 60.6%(20 cases), 33.3%(11 cases), 6.1%(2 cases) and 55.6%(15 cases), 44.4%(12 cases), 0 in EER group and SC group, respectively. The difference between two groups was statistically insignificant. The procedure of EER began with a cystostomy guided by B ultrasound, then an antegrade cystoscopy was performed through the cystostomy while negociating the bladder neck to the proximal side of injured urethra. A ureteral stent was inserted into the broken urethra and retrieved by a forceps through retrograde urethroscopy with another flexible cystoscope. We inserted a guidewire into the ureteral stent before removing it and placed a 16F urethral catheter along the guidewire. We analyzed the difference between two groups including the incidence, the length and the management of urethral stricture and the complexity of urethroplasty if needed. The simple urethroplasty was defined as performing anastomosis after dissection of the bulbar urethral and removing the scar tissue, while the procedure was defined as complex urethroplasty if ancillary procedures, such as separating the corporal bodies and partial pubectomy, was needed.Results:The EER group and SC group had 33 patients and 27 patients, respectively. The mean operation time of EER was (24.5±7.0)minutes and there was no intra-operative complications. Postoperatively, 4 cases of bleeding and 2 cases of UTI were found, which were successfully treated by conservative managements. Twenty-eight out of 33 patients(84.8%) in EER group developed urethral stricture and the mean length of it was (3.10±1.20)cm. However, all patients in SC group developed urethral stricture (100.0%) with the mean stricture length of (3.83±1.18)cm. The difference between two groups in term of the length of stricture was statistically significant ( P=0.026). 24 patients(85.7%) in EER group were treated by urethroplsty, 2 patients(7.1%) with endoscopic urethrotomy and 2 patients (7.1%) with dilation. All were treated with urethroplasty but 2 patients with endoscopic in SC group. In EER group, 8 strictures (33.3%)finished with simple urethroplasty and 16 strictures (66.7%) with complex urethroplasty.While in SC group, 6 strictures(24.0%) completed with simple urethroplasty and 19 strictures (76.0%)with complex urethroplasty. The complexity of urethroplasty performed in EER group was not statistically significant when compared with it in SC group( P=0.538). Conclusions:The procedure of EER with flexible cystoscope is reliable and safe. Most patients with formed urethral stricture after PFUI would be treated with urethroplasty. EER can reduce the urethral stricture formation and may decrease the need of the ancillary procedures during the urethroplasties if needed.

Objective:To analyze the policy tools designed for function orientation and development of China′s infectious disease hospitals, in order to provide references for formulating and optimizing the functional implementation and sustainable development policies of these hospitals.Methods:Consulting the website of Peking University Law and official websites on health, and using such keywords as " medical institutions, infectious diseases, hospitals for infectious diseases, public health emergencies, specialized hospitals", and searching the national policy texts on the functions and development of infectious disease hospitals issued from December 1991 to January 2023. By means of Rothwell and Zegveld′s policy tool classification method, Nvivo 11 Pro software was used to analyze the text content from the dimensions of demand-type, supply-type, and environmental-type policy tools.Results:A total of 41 policy texts were included and 204 codes were obtained through text analysis. Of all the tools, environmental and supply-oriented policy tools were used the most, being 104 (50.99%) and 95 (46.56%) respectively, while demand-oriented policy tools were used the least, only 5 (2.45%). Of all the environmental-oriented policy tools, " goal planning" was the most used, being 34 (16.67%), while " publicity and guidance" was less used, only 4 (1.96%). Among the supply-oriented policy tools, " clarifying the reporting and handling service functions of public health emergencies" was the most widely used, being 34 (16.67%), while " Informationization" and " infrastructure construction" was less used, being 8 (3.92%) and 6 (2.94%) respectively. Few of the demand-oriented policy tools were in use, as " government purchase" and " medical insurance support" were both 2 (0.98% each), and " social medical care" was only 1 (0.49%).Conclusions:The distribution of three types of policy tools for function and development of infectious disease hospitals is unbalanced, the use of environmental and supply-oriented policy tools is excessive and internal structure is unbalanced. The proportion of environmental-oriented policy tools needs to be adjusted, and the frequency of use of supporting tools such as relevant standards, norms, incentives, supervision and publicity should be increased. Supply-oriented policies need to be further optimized, especially in terms of personnel training, funding, information technology and infrastructure construction. Demand-oriented policy tools are seriously underused and need to be further developed.

OBJECTIVE: To review targeted muscle reinnervation (TMR) surgery for the construction of intelligent prosthetic human-machine interface, thus providing a new clinical intervention paradigm for the functional reconstruction of residual limbs in amputees. METHODS: Extensively consulted relevant literature domestically and abroad and systematically expounded the surgical requirements of intelligent prosthetics, TMR operation plan, target population, prognosis, as well as the development and future of TMR. RESULTS: TMR facilitates intuitive control of intelligent prostheses in amputees by reconstructing the "brain-spinal cord-peripheral nerve-skeletal muscle" neurotransmission pathway and increasing the surface electromyographic signals required for pattern recognition. TMR surgery for different purposes is suitable for different target populations. CONCLUSION TMR surgery has been certified abroad as a transformative technology for improving prosthetic manipulation, and is expected to become a new clinical paradigm for 2 million amputees in China.
Humans ; Artificial Limbs ; Muscle, Skeletal ; Neurosurgical Procedures ; Plastic Surgery Procedures ; Prosthesis Implantation

BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration. METHODS: In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining. RESULTS: The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements. CONCLUSION Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.