Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models.

Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1, Rbl1, Pten, and Trp53, which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes.

Bone Marrow Stimulation Does Not Lead to Lower Retear Rates, Better Functional Outcomes, or Higher Complication Rates at Short-Term Follow-Up for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To determine the effect of bone marrow stimulation (BMS) on retear rates, functional outcomes, and complication rates in patients who underwent arthroscopic rotator cuff repair (RCR) through a meta-analysis of randomized controlled trials. METHODS: PubMed, EMBASE, Web of Science, and The Cochrane Library were searched on March 25, 2023. Two evaluators independently screened the literature, extracted data, and assessed the methodologic quality of the enrolled studies. Meta-analysis was conducted using RevMan software, version 5.4. RESULTS: A total of 7 randomized controlled trials with 638 patients were included. The evaluation of rotator cuff tendon integrity was conducted using distinct imaging modalities. Specifically, 259 patients underwent magnetic resonance imaging whereas 208 patients underwent ultrasound. Additionally, a subset of 95 patients underwent either of these modalities; however, the precise distribution between these 2 modalities was not explicitly delineated. Compared with RCR alone, RCR combined with BMS provided similar retear rates (P = .51, I2 = 46%), Constant-Murley scores (P = .14, I2 = 0%), American Shoulder and Elbow Surgeons (standardized shoulder assessment form) scores (P = .56, I2 = 0%), Western Ontario Rotator Cuff Index scores (P = .20, I2 = 0%), visual analog scale scores (P = .19, I2 = 0%), forward flexion (P = .18, I2 = 0%), external rotation (P = .62, I2 = 0%), severe complication rates (P = .56, I2 = 0%), and mild complication rates (P = .10, I2 = 0%). CONCLUSIONS: Compared with the outcomes observed after isolated arthroscopic RCR, arthroscopic RCR with BMS showed comparable results in terms of retear rate, functional outcomes, and incidence of complications. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Lower Reoperation Rate and Superior Patient-reported Outcome Following Arthroscopic Rotator Cuff Repair with Concomitant Acromioplasty: An Updated Systematic Review of Randomized Controlled Trials.

PURPOSE: This study aims to systematically assess the postoperative outcomes in patients undergoing arthroscopic rotator cuff repairs with or without concomitant acromioplasty through a rigorous systematic review of randomized controlled trial s (RCTs). METHODS: This systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, aimed to identify RCTs comparing clinical outcomes of patients with full thickness rotator cuff tears undergoing arthroscopic rotator cuff repair with acromioplasty versus those without at a minimum of 12 months follow-up. Databases searched included PubMed, Web of Science, Embase, and the Cochrane Library. The risk of bias in the included studies was assessed using the revised Cochrane Risk of Bias 2 (RoB2). Meta-analysis was conducted for outcomes with at least three studies reporting, with pooled effect estimates calculated using either fixed-effect or random-effects models based on heterogeneity levels. Results were presented as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). For outcomes with fewer than three studies reporting, a Fisher exact test was conducted, with continuity correction applied if necessary. Primary outcomes include rates of retear and reoperation, while secondary outcomes included improvement in American Shoulder and Elbow Surgeons (ASES) score, range of motion (ROM), and complication rate. RESULTS: Five high-quality RCTs, with low bias risk, involving 409 patients, revealed demographics of 58.4% males, mean age 58.4 years, and acromion types: 12.2% type I, 70.7% type II, and 17.1% type III. Mean follow-up was 52.2 months. Retear (12.5% versus 16.1%, P = 0.536) and complication rates (OR, 3.11; 95% CI, 0.31-30.73; P=0.33) were comparable between the two groups. However, reoperation rate (5.3% versus 15.9%, P < 0.001) and improvement in ASES score (WMD, 3.99; 95% CI, 1.00-6.99; P=0.009) favored the acromioplasty group. Both groups showed significant improvements in ROM, but insufficient data prevented a comparison. CONCLUSIONS: Compared to arthroscopic rotator cuff repair alone, arthroscopic rotator cuff repair with acromioplasty demonstrated similar rates of retear and complications, but a significantly lower reoperation rate and superior improvement in ASES score. The available data were insufficient to draw a definitive conclusion regarding ROM. This conclusion is fragile due to a limited sample size.

Salvage Latarjet may provide worse outcomes in terms of recurrent instability and returning to sports compared to primary Latarjet: a systematic review of comparative studies.

BACKGROUND: The Latarjet procedure (LP) is performed as a primary stabilization procedure (primary LP) and a salvage procedure when an earlier shoulder stabilization procedure has failed (salvage LP). However, whether primary LP or salvage LP provides better outcomes for anterior shoulder instability remains unknown. METHODS: Two independent reviewers performed the literature search based on the PRISMA guidelines. A comprehensive search of PubMed, Embase, web of science and Cochrane Library was performed from their inception date to December 4, 2023. Inclusion criteria mainly included the comparison of postoperative outcomes between primary and salvage LP, English language, and full text availability. Two reviewers independently examined the literature, collected data, and evaluated the methodological robustness of the included studies. The Methodological Index for Nonrandomized Studies was used to evaluate the quality of nonrandomized studies. Recurrent instability, complications, reoperations, return to sports, patient-reported outcomes, and range of motion were assessed. Statistical evaluations were conducted using Manager V.5.4.1 (The Cochrane Collaboration, Software Update, Oxford, UK). RESULTS: Twelve studies were included in the systematic review, with 940 shoulders undergoing primary LP and 631 shoulders undergoing salvage LP. Statistically significant differences in favor of primary LP were found in 2 of the 11 and 2 of 4 included studies in terms of recurrent instability and returning to the same sports (RTS) at preinjury level, respectively. In terms of the visual analog scale, subjective shoulder value and the Western Ontario Shoulder Instability Index, 2 of the 4, 1 of the 3 and 1 of the 3 included studies reported statistically significant differences in favor of primary LP. Differences were not noticed regarding complications, reoperations, the time to RTS, the Rowe score, the Athletic Shoulder Outcome Scoring System, and forward flexion. CONCLUSION: Current evidence suggests that compared with primary LP, salvage LP may provide inferior postoperative outcomes in terms of recurrent instability and the rate of RTS at preinjury level. Primary and salvage LP may yield comparable efficacy in terms of complications, reoperations, the rate of RTS, the time to RTS, pain, shoulder function, and range of motion. PROSPERO ID: CRD42023492027.

Dynamic Mechanical Properties and Modified Johnson-Cook Model Considering Recrystallization Softening for Nickel-Based Powder Metallurgy Superalloys.

The material undergoes high temperature and high strain rate deformation process during the cutting process, which may induce the dynamic recrystallization behavior and result in the evolution of dynamic mechanical properties of the material to be machined. In this paper, the modified Johnson-Cook (J-C) model for nickel-based powder metallurgy superalloy considering dynamic recrystallization behavior in high strain rate and temperature is proposed. The dynamic mechanical properties of the material under different strain rates and temperature conditions are obtained by quasi-static compression test and split Hopkinson pressure bar (SHPB) test. The coefficients of the modified J-C model are obtained by the linear regression method. The modified model is verified by comparison with experimental and model prediction results. The results show that the modified J-C model proposed in this paper can accurately describe the mechanical properties of nickel-based powder metallurgy superalloys at high temperatures and high strain rates. This provides help for studying the cutting mechanism and finite element simulation of nickel-based powder metallurgy superalloy.

Dyslipidemia may impact initial recovery following arthroscopic rotator cuff repair: a retrospective study.

BACKGROUND: The current literature shows that dyslipidemia can lead to a higher incidence of rotator cuff tears (RCTs) and an increased retear rate after repair. We aimed to evaluate the influence of preoperative dyslipidemia on postoperative pain, patient-reported outcomes (PROs), active range of motion (ROM), and structural integrity. METHODS: A cohort of 111 patients who underwent arthroscopic RCT repair between January 2021 and July 2022, and whose complete preoperative serum lipid data were available within one week prior to surgery was retrospectively reviewed. Dyslipidemia was defined as the presence of an increase or decrease in at least one blood lipid profile (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, or non-high-density lipoprotein). There were 43 patients in the dyslipidemia group and 68 in the ortholiposis group. Patient evaluations, including pain score, PROs, and ROMs, were conducted preoperatively; at 3 and 6 months postoperatively; and at the last follow-up. Structural integrity was assessed by magnetic resonance imaging (MRI) 6 months after surgery if possible, and Sugaya type 4 or 5 was considered a retear. Propensity score matching (PSM) was used to reduce bias. RESULTS: The RCT size, surgical technique, preoperative pain status, PROs, and active ROM were comparable between patients with dyslipidemia and those with ortholiposis. Three months after surgery, patients in the dyslipidemia group had worse average PROs (Constant score: P = 0.001; ASES score: P = 0.012; UCLA score: P = 0.015), forward flexion (P = 0.012), and internal rotation (P = 0.001) than patients in the ortholiposis group did. The difference between the two groups persisted after PSM but disappeared at the sixth month after surgery. No significant differences in pain score, PROs, or active ROMs were detected between the dyslipidemia and ortholiposis groups after a mean follow-up of 24 months. Of the 72 patients who underwent MRI, 4 retears (5.6%) were found, and all were in the ortholiposis group. There was no difference in the rate of retears between the two groups (P = 0.291) or with (P = 0.495) PSM. CONCLUSIONS: In conclusion, we found that perioperative dyslipidemia may impact initial recovery within the first 3 months following arthroscopic rotator cuff repair but may have no effect on pain, PROs, or active ROMs at a mean 2-year follow-up or rotator cuff integrity at 6 months postoperatively. Trail registration Retrospectively registered.

Amino acid promoted oxidation of atrazine by Fe3O4/persulfate.

In the present study, we demonstrated that the presence of cysteine could remarkably enhance the degradation of atrazine by Fe3O4/persulfate system. The results of electron paramagnetic resonance (EPR) spectra confirmed the combination of cysteine and Fe3O4 exhibited much higher activity on activation of persulfate to generate more SO4•- and •OH than Fe3O4 alone. At pH of 3.0, SO4•- and •OH contributed to about 58.2 % and 41.8 % of atrazine removal respectively, while •OH gradually dominated the oxidation of atrazine from neutral condition to alkaline condition. The co-existing Cl- and HCO3- could quench SO4•-, resulting in the inhibition of atrazine degradation. The presence of low natural organic matters (NOM) concentration (0-2 mg L-1) could enhance the atrazine removal, and high concentration (>5 mg L-1) of NOM restrained the atrazine degradation. During the Cysteine/Fe3O4/Persulfate process, cysteine served as a complexing reagent and reductant. Through acidolysis and complexation, Fe3O4 could release dissolved and surface bound Fe2+, both of which contributed to the activation of persulfate together. Meanwhile, cysteine was not rapidly consumed due to a regeneration process, which was beneficial for maintaining Fe2+/Fe3+ cycle and constantly accelerating the activation of persulfate for atrazine degradation. The reused Fe3O4 and cysteine in the Cysteine/Fe3O4/Persulfate process exhibited high stability for the atrazine degradation after three cycles. The degradation pathway of atrazine included alkylic-oxidation, dealkylation, dechlorination-hydroxylation processes. The present study indicates the novel Cysteine/Fe3O4/Persulfate process might be a high potential for treatment of organic polluted water.

Backbone cationized highly branched poly(ß-amino ester)s as enhanced delivery vectors in non-viral gene therapy.

Gene therapy holds great potential for treating Lung Cystic Fibrosis (CF) which is a fatal hereditary condition arising from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in dysfunctional CFTR protein. However, the advancement and clinical application of CF gene therapy systems have been hindered due to the absence of a highly efficient delivery vector. In this work, we introduce a new generation of highly branched poly(ß-amino ester) (HPAE) gene delivery vectors for CF treatment. Building upon the classical chemical composition of HPAE, a novel backbone cationization strategy was developed to incorporate additional functional amine groups into HPAE without altering their branching degree. By carefully adjusting the type, proportion, and backbone distribution of the added cationic groups, a series of highly effective HPAE gene delivery vectors were successfully constructed for CF disease gene therapy. In vitro assessment results showed that the backbone cationized HPAEs with randomly distributed 10% proportion of 1-(3-aminopropyl)-4-methylpiperazine (E7) amine groups exhibited superior transfection performance than their counterparts. Furthermore, the top-performed backbone cationized HPAEs, when loaded with therapeutic plasmids, successfully reinstated CFTR protein expression in the CFBE41o- disease model, achieving levels 20-23 times higher than that of normal human bronchial epithelial (HBE) cells. Their therapeutic effectiveness significantly surpassed that of the currently advanced commercial vectors, Xfect and Lipofectamine 3000.

Suture Button Could Result in More Functional Outcomes Improvement and Pain Relief Than Hook Plate Technique for Treating Acute Acromioclavicular Joint Dislocation: A Systematic Review of Comparative Studies.

PURPOSE: To systematically review the current evidence to compare the differences in outcomes of the suture button (SB) versus hook plate (HP) fixations for treating acute acromioclavicular joint dislocation (ACD). METHODS: Two independent reviewers performed the literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of the Embase, PubMed, and Cochrane Library databases was performed and Level I-IV evidence studies comparing the SB and HP procedures for acute ACD were included. Studies that met the following exclusion criteria were excluded: (1) letters, comments, case reports, reviews, animal studies, cadaveric studies, biomechanical studies, and study protocols; (2) incomplete data; and (3) repeated studies and data. The Newcastle-Ottawa Scale was used to evaluate the quality of nonrandomized studies. Constant score, visual analog scale (VAS) score, operation time, coracoclavicular distance (CCD), and complications were recorded and the mean differences of VAS and Constant were compared with preset minimal clinically important difference. RESULTS: Fourteen studies with 363 patients treated with SB procedures and 432 patients with the HP procedure were included. In terms of patient-reported outcomes, 5 of the 13 included studies reported significantly greater Constant score in SB group and most (4/5) used arthroscopic SB technique. Statistically significant differences in favor of SB were found in 3 of the 7 included studies in terms of VAS score whereas none of them reached the minimal clinically important difference. In terms of recurrent instability, no statistically significant difference was noted. All studies showed that the SB technique resulted in lower estimated blood loss. No difference was detected in CCD and complications. CONCLUSIONS: Based on the current body of evidence, it is suggested that employment of the SB technique may confer advantageous outcomes when compared to the HP technique in acute ACD patients. These potential benefits may include higher Constant scores, lower pain levels, and no discernible increases in operation time, CCD, or complication rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level II-IV studies.

What Are the Recurrence Rates, Complications, and Functional Outcomes After Multiportal Arthroscopic Synovectomy for Patients With Knee Diffuse-type Tenosynovial Giant-cell Tumors?

BACKGROUND: Diffuse-type tenosynovial giant-cell tumor (D-TGCT), formerly known as pigmented villonodular synovitis, is a rare, locally aggressive, invasive soft tissue tumor that primarily occurs in the knee. Surgical excision is the main treatment option, but there is a high recurrence rate. Arthroscopic surgical techniques are emphasized because they are less traumatic and offer faster postoperative recovery, but detailed reports on arthroscopic techniques and outcomes of D-TGCT in large cohorts are still lacking. QUESTIONS/PURPOSES: (1) What is the recurrence rate of knee D-TGCT after multiportal arthroscopic synovectomy? (2) What are the complications, knee ROM, pain score, and patient-reported outcomes for patients, and do they differ between patients with and without recurrence? (3) What factors are associated with recurrence after arthroscopic treatment in patients with D-TGCT? METHODS: In this single-center, retrospective study conducted between January 2010 and April 2021, we treated 295 patients with knee D-TGCTs. We considered patients undergoing initial surgical treatment with multiportal arthroscopic synovectomy as potentially eligible. Based on that, 27% (81 of 295) of patients were excluded because of recurrence after synovectomy performed at another institution. Of the 214 patients who met the inclusion criteria, 17% (36 of 214) were lost to follow-up, leaving 83% (178 of 214) of patients in the analysis. Twenty-eight percent (50 of 178) of patients were men and 72% (128 of 178) were women, with a median (range) age of 36 years (7 to 69). The median follow-up duration was 80 months (26 to 149). All patients underwent multiportal (anterior and posterior approaches) arthroscopic synovectomy, and all surgical protocols were determined by discussion among four surgeons after preoperative MRI. A combined open posterior incision was used for patients with lesions that invaded or surrounded the blood vessels and nerves or invaded the muscle space extraarticularly. Standard postoperative adjuvant radiotherapy was recommended for all patients with D-TGCT who had extraarticular and posterior compartment invasion; for patients with only anterior compartment invasion, radiotherapy was recommended for severe cases as assessed by the surgeons and radiologists based on preoperative MRI and intraoperative descriptions. Postoperative recurrence at 5 years was calculated using a Kaplan-Meier survivorship estimator. The WOMAC score (0 to 96, with higher scores representing a worse outcome; minimum clinically important difference [MCID] 8.5), the Lysholm knee score (0 to 100, with higher scores being better knee function; MCID 25.4), the VAS for pain (0 to 10, with higher scores representing more pain; MCID 2.46), and knee ROM were used to evaluate functional outcomes. Because we did not have preoperative patient-reported outcomes scores, we present data on the proportion of patients who achieved the patient-acceptable symptom state (PASS) for each of those outcome metrics, which were 14.6 of 96 points on the WOMAC, 52.5 of 100 points on the Lysholm, and 2.32 of 10 points on the VAS. RESULTS: The symptomatic or radiographically documented recurrence at 5 years was 12% (95% confidence interval [CI] 7% to 17%) using the Kaplan-Meier estimator, with a mean recurrence time of 33 ± 19 months. Of these, three were asymptomatic recurrences found during regular MRI reviews, and the remaining 19 underwent repeat surgery. There was one intraoperative complication (vascular injury) with no effect on postoperative limb function and eight patients with postoperative joint stiffness, seven of whom improved with prolonged rehabilitation and one with manipulation under anesthesia. No postradiotherapy complications were found. The proportion of patients who achieved the preestablished PASS was 99% (176 of 178) for the VAS pain score, 97% (173 of 178) for the WOMAC score, and 100% (178 of 178) for the Lysholm score. A lower percentage of patients with recurrence achieved the PASS for WOMAC score than patients without recurrence (86% [19] versus 99% [154], OR 0.08 [95% CI 0.01 to 0.52]; p = 0.01), whereas no difference was found in the percentage of VAS score (95% [21] versus 99% [155], OR 0.14 [95% CI 0.01 to 2.25]; p = 0.23) or Lysholm score (100% [22] versus 100% [156], OR 1 [95% CI 1 to 1]; p = 0.99). Moreover, patients in the recurrence group showed worse knee flexion (median 135° [100° to 135°] versus median 135° [80° to 135°]; difference of medians 0°; p = 0.03), worse WOMAC score (median 3.5 [0 to 19] versus median 1 [0 to 29]; difference of medians 2.5; p = 0.01), and higher VAS pain score (median 1 [0 to 4] versus median 0 [0 to 4]; difference of medians 1; p < 0.01) than those in the nonrecurrence group, although no differences reached the MCID. No factors were associated with D-TGCT recurrence, including the use of postoperative radiotherapy, surgical technique, and invasion extent. CONCLUSION: This single-center, large-cohort retrospective study confirmed that multiportal arthroscopic surgery can be used to treat knee D-TGCTs with a low recurrence rate, few complications, and satisfactory postoperative outcomes. Surgeons should conduct a thorough preoperative evaluation, meticulous arthroscopic synovectomy, and regular postoperative follow-up when treating patients with D-TGCT to reduce postoperative recurrence. Because the available evidence does not appear to fully support the use of postoperative adjuvant radiotherapy in all patients with D-TGCTs and our study design is inadequate to resolve this controversial issue, future studies should look for more appropriate indications for radiotherapy, such as planning based on a more precise classification of lesion invasion. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Combined Surgical Approach for Recurrent Patellar Dislocation in Adolescents with Patella Alta and Increased Tibial Tuberosity-Trochlear Groove Distance: Improved Clinical Outcomes but Decreased Posterior Tibial Slopes in Skeletally Immature Patients at Minimum Four-Year Follow-up.

PURPOSE: (1) To report the clinical and radiological outcomes of a surgical technique combining anatomic medial patellofemoral ligament reconstruction and tibia tuberosity transfer in adolescents with patella alta and elevated tibial tuberosity-trochlear groove (TT-TG) distance in the treatment of recurrent patellar dislocation (RPD); and (2) To investigate the potential risks of growth arrest or developmental deformities associated with this combined technique. METHODS: Medical records of patients who underwent the combined surgery from 2015 to 2019 were reviewed. This study included adolescents aged between 14 and 18 years with a Caton-Deschamps index (CDI) > 1.30 and TT-TG distance > 20 mm, with a minimum follow-up of 4 years. Radiological examinations including lateral views and full-length posteroanterior standing radiographs were investigated to assess patella height by CDI, posterior tibial slope (PTS) angle, side-to-side difference (SSD) in bone length, and lower extremity alignment by hip-knee-ankle (HKA) angle; computed tomography scans and magnetic resonance imaging (MRI) profiles were investigated to evaluate TT-TG distance and staging of growth plate closure. Other evaluations included preoperative and postoperative physical examination, Kujala score, and Tegner activity score. The patients were stratified into 3 subgroups according to an MRI-based staging system of the growth plate closure, and each outcome was analyzed. A cohort-specific minimal clinically important difference (MCID) estimation was performed using standard error of measurement. RESULTS: The average age at the time of surgery was 16.1 years (range, 14.1-17.8). The average follow-up was 5.6 years (range, 4.0-7.6). No recurrent dislocation occurred, and no clinically significant deformity or axis deviation was encountered. Postoperative patellar height by CDI was 1.00 ± 0.11 (range, 0.81-1.15). No significant differences were found in the preoperative and postoperative HKA angle or SSD in femur/tibia length among all subgroups. A significantly decreased PTS angle was found in patients with open growth plates, from 10.2° ± 1.7° before surgery to 8.1° ± 1.0° after surgery (P = .015). The Kujala score and Tegner score both significantly improved, from 65.5 ± 13.9 before surgery to 90.4 ± 7.2 after surgery in the Kujala score (P < .001) and from 4.0 ± 1.1 before surgery to 4.7 ± 1.3 after surgery in the Tegner score (P < .001). Of the whole cohort, 63.1%, 100%, 47.1%, and 94.1% of patients achieved the MCID for PTS angle, CDI, Tegner score, and Kujala score, respectively. CONCLUSION: This combined technique is safe and effective in treating RPD in skeletally mature adolescents with concurrent patella alta (CDI > 1.30) and TT-TG distance > 20 mm, permitting patients to have improved knee function and low complication rates. Nonetheless, patients with open growth plates demonstrated a decrease in PTS, which might predispose the knee to recurvatum and osteoarthritis in the long term. LEVEL OF EVIDENCE: Level IV, controlled case series.

Parameniscal Cyst Arthroscopic Excision by the Modified Fat Pad Approach Can Shorten Recovery Time-A New Surgical Method with Retrospective Study.

OBJECTIVES: Parameniscal cysts can be removed without meniscectomy, but for large or multiloculated meniscal cysts, traditional arthroscopic excision may leave the meniscus unstable. This study aimed to describe a modified fat pad approach for parameniscal cyst arthroscopic excision that retains a stable structure of the synovial margin of the meniscus and to compare the clinical outcomes between the traditional cyst excision and modified excision techniques. METHODS: Fifty-six patients with parameniscal cysts between 2014 and 2018 were retrospectively included in this study with 28 patients in each group. All patients underwent arthroscopic parameniscal cyst excisions with traditional and modified excision techniques respectively in each group. The International Knee Documentation Committee subjective (IKDC) score, Lysholm score, visual analogue scale (VAS) score, Tegner score, active range of motion (ROM) and time to recover full ROM were used to evaluate the clinical outcomes by using the t-test. RESULTS: The patient population included 21 males and 35 females, with a mean follow-up of 29 months. Of these, 28 patients underwent traditional arthroscopic cyst excisions and meniscal sutures, and 28 patients underwent arthroscopic excisions by the modified fat pad approach. There were no significant differences in the IKDC score, Lysholm score, Tegner score or VAS score between the traditional and modified excision groups at the final follow-up time point. However, the postoperative time to recover full ROM in the modified excision group was significantly lower than those in the traditional excision group (p < 0.05). CONCLUSION: Arthroscopic excision with the modified fat pad approach yielded a shorter pain phase and less time to recover full ROM during recovery compared with the traditional arthroscopic excision. The new method seemed to be effective, as evidenced by the positive clinical outcomes of patients.

One-stage rotator cuff repair in stiff shoulders shows comparable range of motion, clinical outcome and retear rates to non-stiff shoulders: a systematic review.

BACKGROUND: One-stage treatment involving rotator cuff repair and shoulder capsule release is mainly used to treat patients with rotator cuff tears (RCTs) and concomitant shoulder stiffness. Despite the increasing attention to the efficacy and safety of one-stage treatment, controversy still remains. Therefore, this systematic review aims to summarize the indications, operation procedure and rehabilitation protocol, and compare the range of motions (ROMs), functional outcomes and retear rates of one-stage treatment for RCTs in stiff shoulders and non-stiff shoulders. METHODS: Multiple databases (PubMed, the Cochrane Library, Embase and MEDLINE) were searched for studies that investigated outcomes after one-stage treatment for RCTs concomitant with shoulder stiffness compared with rotator cuff repair for RCTs alone, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Descriptive statistics, including range of motion, patient-reported outcome and retear rate, are presented without meta-analysis due to the heterogeneity and low levels of evidence. RESULTS: A total of 9 cohort studies were included, with 305 patients treated with one-stage treatment involving rotator cuff repair and simultaneous shoulder capsular release and 1059 patients treated with rotator cuff repair alone. Patients in both groups had significant symptom improvement and functional recovery after the one-stage treatment for the stiffness group and standard repair for the non-stiffness group, and most patients could return to normal life and work within 6 months after the operation. The retear rate in the one-stage treatment group was not higher than that in the rotator cuff repair group. No statistically significant differences between the two groups were observed in terms of range of motion and patient-reported outcomes in the vast majority of studies at the final follow-up, including the visual analog scale for pain, the Constant score, the American Shoulder and Elbow Surgeons score, the University of California Los Angeles Shoulder Score, the Oxford shoulder score and the Simple Shoulder Test. CONCLUSION: One-stage treatment for RCTs in stiff shoulders provides comparable ROM and patient-reported clinical outcomes as rotator cuff repair for non-stiff RCTs. In addition, the rate of postoperative retear in stiff shoulder treated with one-stage treatment was not higher than in non-stiff shoulders.

Artificial Intelligence (AI)-Aided Structure Optimization for Enhanced Gene Delivery: The Effect of the Polymer Component Distribution (PCD).

Gene therapy has emerged as a significant advancement in medicine in recent years. However, the development of effective gene delivery vectors, particularly polymer vectors, remains a significant challenge. Limited understanding of the internal structure of polymer vectors has hindered efforts to enhance their efficiency. This work focuses on investigating the impact of polymer structure on gene delivery, using the well-known polymeric vector poly(ß-amino ester) (PAE) as a case study. For the first time, we revealed the distinct characteristics of individual polymer components and their synergistic effects-the appropriate combination of different components within a polymer (high MW and low MW components) on gene delivery. Additionally, artificial intelligence (AI) analysis was employed to decipher the relationship between the polymer component distribution (PCD) and gene transfection performance. Guided by this analysis, a series of highly efficient polymer vectors that outperform current commercial reagents such as jetPEI and Lipo3000 were developed, among which the transfection efficiency of the PAE-B1-based polyplex was approximately 1.5 times that of Lipo3000 and 2 times that of jetPEI in U251 cells.

Enhancement of Growth and Synthesis of Extracellular Enzymes of Morchella sextelata Induced by Co-culturing with Trichoderma.

Trichoderma is a genus of common filamentous fungi that display a various range of lifestyles and interactions with other fungi. The interaction of Trichoderma with Morchella sextelata was explored in this study. Trichoderma sp. T-002 was isolated from a wild fruiting body of Morchella sextelata M-001 and identified as a closely related species of Trichoderma songyi based on morphological chracteristics and phylogenetic analysis of translation elongation factor1-alpha and inter transcribed spacer of rDNA. Further, we focussed on the influence of dry mycelia of T-002 on the growth and synthesis of extracellular enzymes of M-001. Among different treatments, M-001 showed the highest growth of mycelia with an optimal supplement of 0.33 g/100 mL of T-002. Activities of extracellular enzymes of M-001 were enhanced significantly by the optimal supplement treatment. Overall, T-002, a unique Trichoderma species, had a positive effect on mycelial growth and synthesis of extracellular enzymes of M-001.

Venous thromboembolism after arthroscopic shoulder surgery: a systematic review.

PURPOSE: To summarize the incidence, risk factors, diagnosis methods, prophylaxis methods, and treatment of venous thromboembolism (VTE) following arthroscopic shoulder surgery. METHODS: Literature on VTE after arthroscopic shoulder surgeries was summarized, and all primary full-text articles reporting at least 1 case of deep vein thrombosis (DVT) or pulmonary embolism (PE) after arthroscopic shoulder surgeries were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, diagnosis, prophylaxis, and management of VTE following arthroscopic shoulder surgeries. RESULTS: This study included 42 articles in which the incidence of VTE ranges from 0 to 5.71% and the overall incidence was 0.26%. Most VTE events took place between the operation day and the 14th day after the operation (35/51). Possible risk factors included advanced age (> 70 years), obesity (BMI ≥ 30 kg/m2), diabetes mellitus, thrombophilia, history of VTE, prolonged operation time, hormone use, and immobilization after surgery. The most common prophylaxis method was mechanical prophylaxis (13/15). No statistical difference was detected when chemoprophylaxis was applied. The management included heparinization followed by oral warfarin, warfarin alone and rivaroxaban, a direct oral anticoagulant. CONCLUSION: Based on the included studies, the incidence rate of VTE after arthroscopic shoulder surgeries is relatively low. The risk factors for VTE are still unclear. CT/CTA and ultrasound were the mainstream diagnosis methods for PE and DVT, respectively. Current evidence shows that chemical prophylaxis did not deliver significant benefits, since none of the existing studies reported statistically different results. High-quality studies focusing on the prophylaxis and management of VTE population undergoing arthroscopic shoulder surgeries should be done in the future.

Platelet-Rich Plasma Injection Can Be a Viable Alternative to Corticosteroid Injection for Conservative Treatment of Rotator Cuff Disease: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To explore whether platelet-rich plasma (PRP) injection can be a viable alternative to corticosteroid (CS) injection for conservative treatment of rotator cuff disease. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, EMBASE, The Cochrane Library, and Web of Science were searched from January 1, 1990, to March 20, 2022, for English-language randomized controlled trials that compared PRP and CS injections for patients with rotator cuff disease. Two evaluators independently screened the literature, extracted data, and assessed the level of evidence and methodologic quality of the enrolled studies. The meta-analysis was conducted using RevMan software (version 5.3.3). RESULTS: Thirteen nonsurgical randomized controlled trials with 725 patients were included. Compared with CS, PRP provided statistically worse short-term (<2 months) changes in American Shoulder and Elbow Surgeons (ASES) assessment scores, Simple Shoulder Test scores, and Disabilities of the Arm, Shoulder and Hand questionnaire scores but provided better medium-term (2-6 months) changes in Disabilities of the Arm, Shoulder and Hand scores, as well as long-term (≥6 months) changes in Constant-Murley scores, ASES scores, and Simple Shoulder Test scores. No statistically significant differences regarding pain reduction were found between the 2 groups. PRP injections led to worse short-term changes in forward flexion and internal rotation but better medium-term changes in forward flexion and external rotation. PRP showed significantly lower rates of post-injection failure (requests for subsequent injections or surgical intervention prior to 12 months) than CS. No outcome reached the minimal clinically important difference. After sensitivity analyses excluding studies with substantial clinical and/or methodologic heterogeneity, PRP showed better medium-term changes in ASES scores and visual analog scale scores and long-term changes in visual analog scale scores that reached the minimal clinically important difference. CONCLUSIONS: Without the drawbacks of CS injection, PRP injection is not worse than CS injection in terms of pain relief and function recovery at any time point during follow-up. PRP injection may reduce rates of subsequent injection or surgery, and it might provide better improvements in pain and function in the medium to long term. PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease. LEVEL OF EVIDENCE: Meta-analysis of Level I and II studies.

[Short-term safety and effectiveness of domestic polyether-ether-ketone suture anchors for rotator cuff repair: A multicenter, randomized, single-blind, parallel-controlled noninferiority study].

Objective: A multicenter, randomized, single-blind, parallel-controlled noninferiority study was used to evaluate the short-term safety and effectiveness of domestic polyether-ether-ketone (PEEK) suture anchor for rotator cuff repair by comparing with the imported PEEK suture anchor commonly used in clinical practice. Methods: A total of 59 patients with rotator cuff tears who were admitted between May 2019 and October 2019 were selected as the research objects. Among them, 3 patients were excluded because they did not meet the selection criteria, and 1 patient withdrew from the study because of serious adverse events. A total of 55 patients were included in the study. They were randomly divided into trial group ( n=27) and control group ( n=28). The trial group used PEEK suture anchors produced from REJOIN Company, and the control group used PEEK suture anchors from American Arthrex Company. Two patients in control group were lost to follow-up. Twenty-seven patients in trial group and 26 patients in control group were included in the final quantitative analysis. There was no significant difference ( P>0.05) in gender, age, disease duration, side and sizes of rotator cuff tears, composition ratio of patients with type 2 diabetes, and preoperative American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score, University of California at Los Angeles (UCLA) score, and visual analogue scale (VAS) score. The patients were followed up regularly after operation. The postoperative follow-up included safety evaluation (complications, anchor position, and anchor bone reaction) and effectiveness evaluation (shoulder joint function and pain scores, rotator cuff integrity based on Sugaya classification criteria). Results: The operations in both groups were successfully completed, and there was no complication related to the operation and suture anchor. All incisions healed by first intention. There was no significant difference in follow-up time between trial group [(5.85±0.77) months] and control group [(5.96±0.72) months] ( t=0.535, P=0.595). MRI examination indicated that the repaired tendons were fixed and the anchors did not get loose or torn. At 1 day, 3 months, and 6 months after operation, there was no patient with grade 3-4 anchor bone reaction in the two groups, and there was no significant difference in the bone reaction grading between groups ( P>0.05). After operation, the VAS scores of the two groups gradually decreased, and the ASES scores, Constant-Murley scores, and UCLA scores gradually increased, and there were significant differences between groups at each time point ( P<0.05). There was no significant difference between groups at different time points ( P>0.05). There was no significant difference in Sugaya classification of rotator cuff integrity at 1 day, 3 months, and 6 months after operation between groups ( P>0.05). Conclusion: The short-term safety and effectiveness of domestic PEEK suture anchors in rotator cuff tear repair are not significant different from those of imported PEEK suture anchors commonly used in clinical practice.