ObjectiveTo enhance the genetic diagnostic yield for fetal short femur length （FL） and to evaluate the integration of whole exome sequencing （WES） with chromosomal abnormality detection in prenatal diagnosis. MethodsA total of 27 mid-to-late trimester fetuses diagnosed with short FL ［FL < 5th percentile for gestational age or < -2 SD （Standard Deviation）］ at the Prenatal Diagnosis And Medical Genetics Center，Shenshan Medical Center，Memorial Hospital of Sun Yat-Sen University between November 2023 and May 2025 were included. Amniotic fluid or umbilical cord blood samples were collected and subjected to chromosomal karyotyping （19cases）， chromosomal microarray analysis （CMA） or low-coverage whole genome copy number variation（CNV-Seq） （27 cases）， and trio-based whole exome sequencing （trio-WES） （27 cases）. The pathogenicity of genetic variants were interpreted according to the American College of Medical Genetics and Genomics （ACMG） guidelines. ResultsTwenty-six genomic variants were detected in 17 of the 26 fetuses， including numerical chromosomal abnormalities （mosaic type）， copy number variations （CNVs）， single nucleotide variants （SNVs） and insertions-deletions （INDELs）. Genomic variants detected in 11 cases could explain the short femur phenotype.The overall diagnostic rate was 11/27， with pathogenic/likely pathogenic variants explaining 9 cases and variants of uncertain significance （VUS） accounting for 1 cases. In addition Chromosomal karyotype analysis revealed chromosome mosaicism explaining 1 case. The diagnostic rate of CNV detection （CMA/CNV-seq） was 2/27， while WES achieved a diagnostic rate of 10/27， with an incremental yield of 8/27 in cases with negative or inconclusive CNV results. Pathogenic mutations involved genes such as FGFR3， SHOX， DUOX2， CLCN5， and HBA1/HBA2. ConclusionTrio-WES significantly improves the genetic diagnostic rate for fetal short femur length， particularly in cases where chromosomal analysis fails to identify a cause. Karyotyping remains valuable for detecting low-level mosaicism in large-scale chromosomal abnormalities， thereby complementing WES and CNV detection. A stepwise or parallel genetic testing strategy is recommended in prenatal diagnosis to optimize diagnostic efficiency and support clinical decision-making.

Objective:To observe the expression level of long noncoding RNA RP11-97C16.1 in bladder cancer tissues and its relationship with the survival time of bladder cancer patients, and to explore the role and potential molecular mechanism of RP11-97C16.1 in the proliferation of bladder cancer cells.Methods:The expression difference of RP11-97C16.1 in bladder cancer tissue and adjacent tissue was analyzed by TCGA database, and the relationship between the expression level of RP11-97C16.1 and the survival time of bladder cancer patients was analyzed by GEPIA database. The expression of RP11-97C16.1 in four bladder cancer cell lines (T24, MGH-U3, J82, UM-UC-3) was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The UM-UC-3 cells were divided into RP11-97C16.1 group and control group, and the transfectants were pcDNA-RP11-97C16.1 plasmid and negative control plasmid, respectively. The expression levels of RP11-97C16.1 and miR-3687 were detected by RT-qPCR. The viability and proliferation ability of UM-UC-3 cells were detected by cell counting kit-8 (CCK8) and colony formation assay. The complementary relationship between RP11-97C16.1 and miR-3687 was verified by dual-luciferase reporter gene assay. The expression levels of Cyclin E2, CDK2, CDK4, CDK6 and Cyclin D2 were detected by Western blotting. Measurement data were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, the expression of RP11-97C16.1 in bladder cancer tissues was significantly decreased ( P<0.01). Compared with patients with lower expression of RP11-97C16.1, patients with higher expression of RP11-97C16.1 had longer overall survival time ( P<0.01). Compared with the SV-HUC-1 cell line, the expression of RP11-97C16.1 was significantly decreased in the four bladder cancer cell lines ( P<0.01). In UM-UC-3 cells in which RP11-97C16.1 was upregulated, the expression of miR-3687 was decreased ( P<0.01). Compared with the control group, up-regulation of RP11-97C16.1 could significantly reduce the proliferation ability of UM-UC-3 cells ( P<0.05), and decrease the number of bladder cancer cell colonies ( P<0.01). RP11-97C16.1 could target and bind miR-3687 ( P<0.01). Compared with the control group, overexpression of RP11-97C16.1 could significantly decreased the expression of Cyclin E2, CDK2, CDK4, CDK6, and Cyclin D2 proteins. Conclusions:The expression of RP11-97C16.1 is low in bladder cancer tissue, and patients with higher expression of RP11-97C16.1 have a longer survival time. Up-regulation of RP11-97C16.1 can down-regulate the expression of miR-3687, thereby inhibiting the proliferation of bladder cancer cells UM-UC-3.

With obesity rates climbing worldwide, metabolic and bariatric surgery has evolved over seven decades into a pivotal therapeutic approach for treating severe obesity and related disorders. Recent research highlights that new anti-diabetic and weight-loss drugs, especially GLP-1 receptor agonists (GLP-1 RA), are catalyzing a paradigm shift in obesity management. Within this context, the key scientific challenge in metabolic surgery is thoroughly investigating how pharmacological interventions and surgical procedures work together in weight management, especially evaluating if new drugs can match bariatric surgery's long-term effectiveness, complication management, and metabolic changes. Resolving this interdisciplinary debate will influence precision medicine in obesity treatment and reshape future multidisciplinary care models for metabolic disorders.

Objective To evaluate"sequential theory"combined with"clinical simulation"method in teaching ultrasound-guided musculoskeletal intervention therapy.Methods Thirty-four students who participated in the"Musculoskeletal Ultrasound and New Technology Excellent Class"organized by the Department of Ultrasound Medicine of Peking University Third Hospital from November 20 to November 24,2023 were selected as the study objects.After"sequential theory"and"clinical simulation"training,the trainees joined theoretical exami-nation,ultrasound operation and model puncture examination,then a questionnaire survey was carried out.Results The theoretical and practical test scores of 34 students were all qualified,and there was no statistical difference in theoretical and practical test results among students with different educational backgrounds,profes-sional titles and whether they came from basic hospitals.The questionnaire showed that the students were satisfied with the content of the class.Conclusions The application of"sequential theory"and"clinical simulation"methods improves training outcomes of musculoskeletal ultrasound interventional therapy and shortens the learning curve of students.

Objective To investigate the effect of Gd-hydroxyapatite(Gd-HA)stents with adipose mesenchymal cells(ADSCs)on the repair of knee articular cartilage defects.Methods To isolate,culture,and identify rabbit ADSCs by establishing a rabbit knee joint full-thickness cartilage defect model,a total of 18 rabbits were randomly divided into blank control group,Gd-HA scaffold group,and ADSCs+Gd-HA scaffold group.At week 12 and 24 after surgery,International Curtilage Repair Society(ICRS)score,HE,toluidine blue,modified red O bright green and ColⅡ were detected by immunohistochemical staining,then ColⅡand GAG mRNA expression levels were detected by O'Driscoll and Real-time PCR.ColⅡ protein expression was detected by Western blotting,GAG content was detected by DMMB,biomechanical strength was detected by indentation test,and PKH26 labeled ADSCs was used to trace the tissue engineering scaffold with Gd-HA composite ADSCs to evaluate the repair effect of rabbit knee cartilage defects.Results The ADSCs isolated and cultured in vitro showed good growth,stable phenotype and good directional differentiation through macroscopic observation and histological staining,it could be seen that the repair degree and effect of the knee joint full-thickness cartilage defect model implanted with Gd-HA scaffold group were better than those of the blank control group,while the cartilage repair situation of the ADSCs+Gd-HA scaffold group was better than that of the Gd-HA scaffold group(P＜0.05);The ICRS and improved O'Driscoll scores were higher than the other two groups(P＜0.05).Compared with the Gd-HA group,the ADSCs+Gd-HA group could produce ColⅡ and GAG during the process of cartilage repair,with stronger mechanical strength of the repaired tissue(P＜0.05);PKH26 labeled ADSCs were found in the repaired tissues of the ADSCs+Gd-HA group,and they were involved in the composition of newly formed tissues.Conclusion Gd-HA scaffold material combined with ADSCs has a good repair effect on full-thickness cartilage defects in the knee joint as a new type of biological material for repairing joint cartilage defects.

Objective:To evaluate the relevant factors to optimize the learning curve and the impact of the basic skills of endoscopic technology on the learning curve of gasless transaxillary posterior endoscopic thyroidectomy.Methods:A retrospective analysis was performed to evaluate the clinical outcomes of 50 patients who underwent Glandular Ultrasound-Assisted (GUA) thyroid surgery by a surgeon with a background in endoscopic thyroid surgery via the thoracic-areolar approach, and 50 patients operated on by a surgeon without such experience at the Thyroid Surgery Department of Jilin University China-Japan Union Hospital from Apr. to Dec. 2023. The patients were divided into two groups: the Endoscopic Experience Group and the Non-Endoscopic Experience Group. The Cumulative Sum Control Chart (CUSUM) was applied to construct learning curves for both groups, dividing the technical exploration period from the mastery period. The analysis compared the surgical time, postoperative first-day drainage volume, number of central lymph nodes dissected rates, and postoperative complications between the two groups and across the two phases.Results:The analysis of the learning curve revealed that the inflection point of the Endoscopic Experience Group was 15, while of the Non-Endoscopic Experience Group was 18. The learning curve was divided into the technical exploration stage and the proficient mastery stage. The operative time of technical exploration stagde was significantly longer than of proficient mastery stage of both group (183.46±36.13min vs.144.40±26.14min, P<0.001; 186.89±48.91min vs.131.59±22.90min; P<0.001) . The operative time in the proficient mastery stage of the Endoscopic Experience Group was longer than that of the Non-Endoscopic Experience Group (144.40±26.15min vs. 131.59±22.90min, P<0.05) . The postoperative drainage volume in the Endoscopic Experience Group was lower than that in Non-Endoscopic Experience Group in both stages (65.40±32.48mL vs.93.22±30.67mL, 57.40±15.35mL vs.78.50±28.30mL, P<0.05) , and the postoperative drainage volume in the proficient mastery stage of the Non-Endoscopic Experience Group was significantly lower than in the technical exploration stage (93.22±30.67mL vs.78.50±28.30mL, P<0.05) .No significant differences in central lymph node dissection numbers or postoperative complications were observed between the groups at both stages. Conclusions:There is a specific learning curve in the early stage of gasless transaxillary posterior endoscopic thyroidectomy. After crossing the learning curve, the operation time is obviously shortened with the improvement of the operator's surgical technique.Having a basic understanding of endoscopic technology in the early stage can reduce the occurrence of postoperative drainage, but has a minimal impact on the learning curve.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002). CONCLUSION In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans ; Bone Nails/adverse effects* ; Bone Plates/adverse effects* ; Femoral Fractures/surgery* ; Fracture Fixation, Intramedullary/methods* ; Fractures, Ununited/surgery* ; Lower Extremity/injuries*

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

With the increasing use of nirmatrelvir-ritonavir in older COVID-19 patients, adverse drug reactions due to drug-drug interactions have become more frequent. This report describes a patient who experienced severe bradycardia and hypotension following the concurrent use of heart rate-control medications and nirmatrelvir-ritonavir during an active COVID-19 infection. This suggests that clinicians should be cautious when dealing with nirmatrelvir-ritonavir and try their best to avoid serious adverse reactions.