Health impact assessment of the surface water pollution in China.

China suffers from severe surface water pollution. Health impact assessment could provide a novel and quantifiable metric for the health burden attributed to surface water pollution. This study establishes a health impact assessment method for surface water pollution based on classic frameworks, integrating the multi-pollutant city water quality index (CWQI), informative epidemiological findings, and benchmark public health information. A relative risk level assignment approach is proposed based on the CWQI, innovatively addressing the challenge in surface water-human exposure risk assessment. A case study assesses the surface water pollution-related health impact in 336 Chinese cities. The results show (1) between 2015 and 2022, total health impact decreased from 3980.42 thousand disability-adjusted life years (DALYs) (95 % Confidence Interval: 3242.67-4339.29) to 3260.10 thousand DALYs (95 % CI: 2475.88-3641.35), measured by total cancer. (2) The annual average health impacts of oesophageal, stomach, colorectal, gallbladder, and pancreatic cancers added up to 2621.20 thousand DALYs (95 % CI: 2095.58-3091.10), revealing the significant health impact of surface water pollution on digestive cancer. (3) In 2022, health impacts in the Beijing-Tianjin-Hebei and surroundings, the Yangtze River Delta, and the middle reaches of the Yangtze River added up to 1893.06 thousand DALYs (95 % CI: 1471.82-2097.88), showing a regional aggregating trend. (4) Surface water pollution control has been the primary driving factor to health impact improvement, contributing -3.49 % to the health impact change from 2015 to 2022. It is the first city-level health impact map for China's surface water pollution. The methods and findings will support the water management policymaking in China and other countries suffering from water pollution.

N6-Methyladenosine (m6A) Methylation Is Associated with the Immune Microenvironments in Acute Intracerebral Hemorrhage (ICH).

Researchers have recently found that N6-methyladenosine (m6A) is a type of internal posttranscriptional modification that is essential in mammalian mRNA. However, the features of m6A RNA methylation in acute intracerebral hemorrhage (ICH) remain unknown. To explore differential methylations and to discover their functions in acute ICH patients, we recruited three acute ICH patients, three healthy controls, and an additional three patients and healthy controls for validation. The m6A methylation levels in blood samples from the two groups were determined by ultrahigh-performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was employed to identify differences in m6A modification, and the differentially expressed m6A-modified genes were confirmed by MeRIP-qPCR. We found no significant differences in the total m6A levels between the two groups but observed differential methylation peaks. Compared with the control group, the coding genes showing increased methylation following acute ICH were mostly involved in processes connected with osteoclast differentiation, the neurotrophin signaling pathway, and the spliceosome, whereas genes with reduced m6A modification levels after acute ICH were found to be involved in the B-cell and T-cell receptor signaling pathways. These results reveal that differentially m6A-modified genes may influence the immune microenvironments in acute ICH.

Hyperthyroidism with papillary thyroid carcinoma in HIV: Case report and literature review.

The immune function of HIV infected patients is severely damaged, which can cause a series of autoimmune related diseases including hyperthyroidism. Hyperthyroidism includes both primary and secondary hyperthyroidism. Graves' disease is the most common primary hyperthyroidism, and Graves' disease may occur in HIV patients during immune reconstitution after antiretroviral therapy A 47-year-old woman with a history of HIV presented with symptoms related to hyperthyroidism. After antithyroid drug therapy failed, the patient and her families opted for surgical treatment. Postoperative examination revealed papillary thyroid carcinoma.

Validation of ESM1 Related to Ovarian Cancer and the Biological Function and Prognostic Significance.

Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.

Clinical and Second-look Arthroscopic Results for Derotational Distal Femoral Osteotomy With Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation With Increased Femoral Anteversion: A Series of 102 Cases With a Minimum Clinical Follow-up of 2 Years.

BACKGROUND: Derotational distal femoral osteotomy (DDFO) has been used to treat patients with recurrent patellar dislocation (RPD) with increased femoral anteversion. However, no study has reported second-look arthroscopic findings in the patellofemoral joint after DDFO. PURPOSE: To report clinical and second-look arthroscopic outcomes for DDFO with combined medial patellofemoral ligament reconstruction (MPFL-R) in treating RPD with increased femoral anteversion. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From 2015 to 2019, 131 consecutive patients (144 knees) with RPD were treated with combined MPFL-R and DDFO. Patients with a femoral anteversion angle >30° and a minimum 2-year clinical follow-up period were included in the study. Three-dimensional computed tomography was performed to evaluate rotational deformities of the lower leg. Radiographic parameters presenting bony abnormalities associated with RPD were measured. Second-look arthroscopic evaluations were available for 86 knees to assess patellar tracking and chondral lesion changes. Moreover, clinical and radiologic outcomes were assessed pre- and postoperatively at a minimum 2 years. RESULTS: A total of 102 knees in 92 patients were included in the present study with a mean clinical follow-up of 4.1 years (range, 2.0-5.6 years). Mean ± SD femoral anteversion changed significantly from 34.7°± 7.5° preoperatively to 11.3°± 0.2° postoperatively (P < .001), and mean tibial tubercle-trochlear groove distance decreased significantly from 19.6 ± 3.5 mm preoperatively to 17.4 ± 3.2 mm postoperatively (P < .001). In the majority of knees, at the time of second-look arthroscopic assessment, chondral lesion status remained unchanged at the lateral patellar facet (96%) and trochlear groove (95%); in contrast, chondral damage at the medial patellar facet was aggravated in 9 cases (10%). All functional scores (Tegner, Lysholm, visual analog scale, and Kujala scores) improved significantly at final follow-up. None of the patients experienced redislocation or subluxation after surgery. CONCLUSION: Chondral lesions in the patellofemoral joint remained unchanged in the majority of cases in second-look arthroscopy after combined MPFL-R and DDFO. Moreover, high-grade trochlear dysplasia and arthroscopic residual patellar maltracking might be associated with cartilaginous deterioration at the medial patellar facet after surgery.

Outcomes of transarterial embolization for large symptomatic focal nodular hyperplasia in 17 pediatric patients.

BACKGROUND: To evaluate the safety and the long-term outcomes of transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus N-Butyl cyanoacrylate (NBCA) in the treatment of children with large symptomatic focal nodular hyperplasia (FNH). METHODS: This is a retrospective case serial study. Children (aged <18 years) with FNH were treated. Indications for TAE were patients who were presenting with FNH related abdominal pain and the maximum diameter of FNH is more than 7 cm, and who were not candidates for surgical treatment. Technical success, adverse events, symptoms relief rate, and changes in the lesion size after TAE were evaluated. RESULTS: Between January 2003 and February 2018, 17 pediatric patients were included. Technical success was achieved in all patients. Mean follow-up was 67.5 months. All patients had complete resolution of abdominal symptom. The mean largest diameter of the lesions decreased from 10.5 cm to 1.9 cm (P < 0.01). The mean volume reduction rate was 96.9%. The complete resolution of the FNH was observed in 16 patients. No further therapy was needed for all patients. CONCLUSIONS: TAE with LBE plus NBCA appears to be a safe and effective treatment in pediatric patients with large symptomatic FNH. It could be considered as the first-line treatment for symptomatic large FNH.

Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood-testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.

Predictors of Graft Failure After Primary Medial Patellofemoral Ligament Reconstruction.

Background: The tibiofemoral rotation angle has been found to be higher in patients with recurrent patellar dislocations (RPDs) than in healthy people; however, little is known about the clinical significance of this finding. Purpose: To determine whether an increased tibiofemoral rotation angle is associated with graft failure after primary medial patellofemoral ligament reconstruction (MPFL-R) and to investigate the role of the tibiofemoral rotation angle in predicting MPFL-R failure in patients with RPDs. Study Design: Case-control study; Level of evidence, 3. Methods: We retrospectively analyzed the records of 632 consecutive patients with clinically diagnosed RPDs from 2011 to 2018. Postoperative stress radiography of the patellofemoral joint was performed to identify whether the graft failed. After a review, 33 patients who showed MPFL-R failure were allocated to the failure group. They were matched 1:2 to 66 participants who underwent successful MPFL-R (control group). The cutoff value and area under the curve (AUC) of the tibiofemoral rotation angle for predicting graft failure after primary MPFL-R were determined, and the risk factors for MPFL-R failure were assessed by multivariate logistic regression analysis. Results: The tibiofemoral rotation angle was significantly higher in the failure group than in the control group (16.4° ± 5.6° vs 6.4° ± 4.5°, respectively; P < .001). The cutoff value of the tibiofemoral rotation angle for predicting graft failure was 12.3° (sensitivity, 81.8%; specificity, 89.4%; AUC, 0.920). Overall, 3 risk factors for MPFL-R failure were determined: excessive tibiofemoral rotation (≥12.3°) (odds ratio [OR], 13.159 [95% CI, 2.469-70.139]; P = .003), a preoperative high-grade J-sign (OR, 7.674 [95% CI, 1.232-47.809]; P = .029), and a femoral tunnel malposition (OR, 6.976 [95% CI, 1.077-45.187]; P = .042). Conclusion: In this study, excessive tibiofemoral rotation, a preoperative high-grade J-sign, and a femoral tunnel malposition were identified as risk factors for graft failure after primary MPFL-R in patients with RPDs. More importantly, excessive tibiofemoral rotation ( ≥ 12.3°) may predict the failure of primary MPFL-R, which can help surgeons easily identify high-risk patients of MPFL-R failure before surgery.

Aerosol Iron Solubility Specification in the Global Marine Atmosphere with Machine Learning.

Aerosol iron (Fe) solubility is a key factor for the assessment of atmospheric nutrients input to the ocean but poorly specified in models because the mechanism of determining the solubility is unclear. We develop a deep learning model to project the solubility based on the data that we observed in a coastal city of China. The model has five variables: the size range of particles, relative humidity, and the ratios of sulfate, nitrate and oxalate to total Fe (TFe) contents in aerosol particles. Results show excellent statistical agreements with the solubility in the literature over most worldwide seas and margin areas with the Pearson correlation coefficients (r) as large as 0.73-0.97. The exception is the Atlantic Ocean, where good agreement is obtained with the model trained using local data (r: 0.34-0.66). The model further uncovers that the ratio of oxalate/TFe is the most important variable influencing the solubility. These results indicate the feasibility of treating the solubility as a function of the six factors in deep learning models with careful training and validation. Our model and projected solubility provide innovative options for better quantification of air-to-sea input of aerosol soluble Fe in observational and model studies in the global marine atmosphere.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

Fine particulate matter exposure aggravates ischemic injury via NLRP3 inflammasome activation and pyroptosis.

AIMS: Accumulating evidence has suggested that airborne fine particulate matter (PM2.5) exposure is associated with an increased risk of ischemic stroke. However, the underlying mechanisms have not been fully elucidated. In this study, we aim to investigate the role and mechanisms of NLRP3 inflammasome and pyroptosis in ischemic stroke after PM2.5 exposure. METHODS: The BV-2 and HMC-3 microglial cell lines were established and subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) with or without PM2.5 exposure. We used the CCK-8 assay to explore the effects of PM2.5 on cell viability of BV-2 and HMC-3 cells. Then, the effects of PM2.5 exposure on NLRP3 inflammasome and pyroptosis following OGD/R were detected by western blotting, ELISA, and the confocal immunofluorescence staining. Afterwards, NLRP3 was knocked down to further validate the effects of PM2.5 on cell viability, NLRP3 inflammasome activation, and pyroptosis after OGD/R in HMC-3 cells. Finally, the intracellular reactive oxygen species (ROS) was measured and the ROS inhibitor N-acetyl-L-cysteine (NAC) was used to investigate whether ROS was required for PM2.5-induced NLRP3 inflammasome activation and pyroptosis under ischemic conditions. RESULTS: We found that PM2.5 exposure decreased the viability of BV-2 and HMC-3 cells in a dose- and time-dependent manner under ischemic conditions. Furthermore, PM2.5 exposure aggravated NLRP3 inflammasome activation and pyroptosis after OGD/R, as indicated by an increased expression of NLRP3, ASC, pro-caspase-1, Caspase-1, GSDMD, and GSDMD-N; increased production of IL-1ß and IL-18; and enhanced Caspase-1 activity and SYTOX green uptake. However, shRNA NLRP3 treatment attenuated the effects of PM2.5 on cell viability, NLRP3 inflammasome activation, and pyroptosis. Moreover, we observed that PM2.5 exposure increased the production of intracellular ROS following OGD/R, while inhibiting ROS production with NAC partially attenuated PM2.5-induced NLRP3 inflammasome activation and pyroptosis under ischemic conditions. CONCLUSION: These results suggested that PM2.5 exposure triggered the activation of NLRP3 inflammasome and pyroptosis under ischemic conditions, which may be mediated by increased ROS production after ischemic stroke. These findings may provide a more enhanced understanding of the interplay between PM2.5 and neuroinflammation and cell death, and reveal a novel mechanism of PM2.5-mediated toxic effects after ischemic stroke.

Dosage Strategy of Linezolid According to the Trough Concentration Target and Renal Function in Chinese Critically Ill Patients.

Background: Linezolid is associated with myelosuppression, which may cause failure in optimally treating bacterial infections. The study aimed to define the pharmacokinetic/toxicodynamic (PK/TD) threshold for critically ill patients and to identify a dosing strategy for critically ill patients with renal insufficiency. Methods: The population pharmacokinetic (PK) model was developed using the NONMEM program. Logistic regression modeling was conducted to determine the toxicodynamic (TD) threshold of linezolid-induced myelosuppression. The dosing regimen was optimized based on the Monte Carlo simulation of the final model. Results: PK analysis included 127 linezolid concentrations from 83 critically ill patients at a range of 0.25-21.61 mg/L. Creatinine clearance (CrCL) was identified as the only covariate of linezolid clearance that significantly explained interindividual variability. Thirty-four (40.97%) of the 83 patients developed linezolid-associated myelosuppression. Logistic regression analysis showed that the trough concentration (Cmin) was a significant predictor of myelosuppression in critically patients, and the threshold for Cmin in predicting myelosuppression with 50% probability was 7.8 mg/L. The Kaplan-Meier plot revealed that the overall median time from the initiation of therapy to the development of myelosuppression was 12 days. Monte Carlo simulation indicated an empirical dose reduction to 600 mg every 24 h was optimal to balance the safety and efficacy in critically ill patients with CrCL of 30-60 ml/min, 450 mg every 24 h was the alternative for patients with CrCL <30 ml/min, and 600 mg every 12 h was recommended for patients with CrCL ≥60 ml/min. Conclusion: Renal function plays a significant role in linezolid PKs for critically ill patients. A dose of 600 mg every 24 h was recommended for patients with CrCL <60 ml/min to minimize linezolid-induced myelosuppression.

ROS-responsive nanoparticles for oral delivery of luteolin and targeted therapy of ulcerative colitis by regulating pathological microenvironment.

Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development of ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated with a d-α-tocopherol polyethylene glycol succinate-b-poly(ß-thioester) copolymer (TPGS-PBTE) for ROS cleavage via the colitis-targeted delivery of luteolin (LUT), a natural flavonoid with good anti-inflammation and radical-scavenging activity. Owing to the thioether bond in the polymer main chain, the TPGS-PBTE NPs exhibited an ROS-responsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon. In a dextran sulfate sodium-induced acute colitis murine model, LUT@TPGS-PBTE NPs alleviated body weight loss, colon length shortening, and damage to the colonic tissues due to the suppression of ROS and proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), as well as upregulation of glutathione and anti-inflammatory factors (e.g., IL-10, IL-4). More importantly, LUT@TPGS-PBTE NPs regulated the inflammatory microenvironment by modulating the T helper (Th)1/Th2 and Th17/regulatory T cell (Treg) balance (i.e., increased numbers of Tregs and Th2 cells and decreased numbers of Th1 and Th17 â€‹cells), thus resolving inflammation and accelerating the healing of the intestinal mucosa. Additionally, the LUT@TPGS-PBTE NPs formulation enabled the reduction of the effective dose of LUT and showed excellent biosafety in the mouse model, demonstrating its potential as a targeted UC therapeutic oral preparation.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Posterior tibial slope measurements based on the full-length tibial anatomic axis are significantly increased compared to those based on the half-length tibial anatomic axis.

PURPOSE: This study aimed to compare the difference in posterior tibial slope (PTS) measurements based on the full-length and half-length tibial anatomic axes of the same group of patients. It was hypothesized that the obtained PTS values would be affected by the length of tibia chosen during the measurements. METHODS: Full-length true lateral tibia radiographs were obtained for each patient who underwent anterior cruciate ligament reconstruction (ACLR) in our department. PTS measurements were obtained by measuring the angle between the full-length or half-length tibial anatomic axis and an average of the lateral and medial tibial plateau. The anatomic axis was defined as the center of the tibial diaphysis. The PTS measurements from the full-length and half-length true lateral tibia radiographs were obtained and compared. Additionally, the absolute difference and the relationship between the two PTS measurements were calculated and analyzed. RESULTS: A total of 200 ACL-injured patients were included in this study. The average PTS values using the anatomic axis were 15.9 ± 3.7° and 14.1 ± 3.7° on full-length and half-length true lateral tibial radiographs. There was a significant difference between the measurements with the full-length and half-length tibial radiographs (P < 0.01). Additionally, 49.5% (n = 99) of patients had ≥ 2.0° differences between the full-length and half-length anatomic axis PTS measurement techniques; meanwhile, a strong and significant linear relationship (r = 0.95; P < 0.001) was identified between the two PTS measurements. CONCLUSION: There were significant differences and linear relationships between PTS measurements that measured the anatomic axis from full-length and half-length true lateral tibia radiographs. Therefore, the obtained PTS values were strongly associated with the length of tibia chosen during the measurements. Surgeons should pay more attention to the measurement techniques and the tibial length when considering the role of PTS in ACL injury and ACLR failure. Knowledge of the association is very important for calculating potential closing wedge proximal tibial osteotomies to correct excessive PTS in the setting of ACLR failures. LEVEL OF EVIDENCE: IV.

Uterine Artery Embolization with Small-Sized Particles for the Treatment of Symptomatic Adenomyosis: A 42-Month Clinical Follow-Up.

PURPOSE: To assess the long-term outcome of performing uterine artery embolization (UAE) using small particles in women with symptomatic adenomyosis (AD). METHODS: Twenty-seven consecutive women (median age 42 years, range 29-53 years) with AD, in eight cases AD combined with fibroids, who underwent UAE between February 2015 and January 2019, were retrospectively analyzed. The embolization was performed using small-sized polyvinyl alcohol particles (100 µm and 300 µm). The patients completed the Uterine Fibroid Symptom and Quality of Life questionnaire at baseline and at a 42-month follow-up (range 24-71). The junction zone (JZ) thickness and uterine volume were also calculated at baseline and at a three-month follow-up. RESULTS: The total symptom severity score (SSS) decreased from a median of 59 (range 34-78) at baseline to a median of 9 (range 3-47) at the end of this study; the health-related quality of life score (HRQOL) increased from a median of 38 (range 23-49) at baseline to a median of 84 (range 46-97) at 42 months. Twenty of the 27 patients were asymptomatic. The clinical response of the remaining seven women was little improvement in their symptoms, and one of the seven women underwent a hysterectomy at 35 months. Twenty-six of the 27 (96%) patients had a preserved uterus at the 42-month follow-up. There was no difference after UAE in SSS, HRQOL, junction zone (JZ) thickness, and uterus volume between patients with pure AD and those with AD combined with fibroids (p = 0.729, 0.710, 0.973, and > 0.99). There was no difference in the JZ thickness and uterus volume at baseline between the asymptomatic women and the women with an insufficient response (p = 0.854 and 0.253), and there were no major complications afterwards. CONCLUSION: From the long-term follow-ups, it could be seen that UAE using small particles is safe and effective in treating AD, especially in preserving the uterus. There is no relationship between the clinical outcomes and the initial presence of AD, with or without fibroids, and the JZ thickness at baseline does not seem to be a predictor for the long-term outcome of UAE.

Increased Posterior Tibial Slope Is Associated With Greater Risk of Graft Roof Impingement After Anatomic Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Increased posterior tibial slope (PTS) has been reported to be associated with irreducible anterior tibial subluxation in extension after anatomic anterior cruciate ligament (ACL) reconstruction (ACLR), which raises concerns about the greater risk of graft roof impingement (GRI) although the tibial tunnel is positioned anatomically. HYPOTHESIS: Increased PTS would be associated with greater risk of GRI after anatomic ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Between January 2016 and December 2017, a total of 418 consecutive patients were diagnosed as having noncontact ACL injuries and underwent primary anatomic ACLR. Among them, 26 patients had ≥1 of the following features during the second-look arthroscopy: fractured/guillotined bundles at the tibial insertion or cyclops lesion. These patients were confirmed to have GRI and were allocated to the study group. They were also matched 1:2 to 52 control participants without GRI. PTS was measured on true lateral whole-leg radiographs. Intra-articular ACL graft signal intensity was evaluated on postoperative magnetic resonance imaging scans (mean, 32.8 months; range, 26-38 months) and divided into 3 grades (I, good; II, moderate; III, poor) based on degree of GRI. Moreover, anterior subluxation of the lateral compartment (ASLC) and medial compartment (ASMC) in extension relative to the femoral condyles were measured on postoperative magnetic resonance imaging scans and compared between the groups. In addition, predictors of GRI were evaluated using multivariate logistic regression analysis and included body mass index, PTS, pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears. RESULTS: PTS in the study group was significantly higher than that in control group (mean ± SD, 13.8°± 1.5° vs 9.5°± 1.8°; P < .05). In the study group (n = 26), patients with grade III (poor) graft signal intensity (n = 9) showed significantly higher PTS than those with grade II (moderate; n = 17) (16.4°± 1.7° vs 12.4°± 1.3°; P < .05). Moreover, the mean postoperative ASLC and ASMC in extension were significantly larger in the study group than the control group (ASLC, 4.1 ± 1.3 vs 0.8 ± 0.4 mm; ASMC, 4.3 ± 1.5 vs 0.9 ± 0.3 mm; P < .05). Furthermore, the abnormal degree of PTS (≥12°) was determined to be an independent risk factor associated with GRI after anatomic ACLR (odds ratio, 9.0 [95% CI, 3.7-30.2]; P < .001), whereas body mass index, grade of pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears were not. CONCLUSION: Increased PTS (≥12°) was associated with greater risk of GRI after anatomic ACLR. This may provide additional information for counseling patients with greater risk of GRI.

Histological Characteristics of Skin Treated With a Fractionated 1064-nm Nd: YAG Picosecond Laser With Holographic Optics.

BACKGROUND AND OBJECTIVES: Picosecond lasers (PSL) constitute a significant technological advancement and exert rejuvenating effects upon the skin. This study was conducted to investigate changes in the skin upon treatment with the fractionated 1064-nm Nd: YAG PSL through in vivo and ex vivo human histological analysis. STUDY DESIGN/MATERIALS AND METHODS: In vivo back skin specimens were treated with a fractionated 1064-nm PSL at 1.3, 2.1, and 2.9 mJ fluence for two passes, and 2.9 mJ for 10 passes, and then stained with hematoxylin and eosin (H&E). Ex vivo foreskin specimens after circumcision surgery were treated with a PSL at 1.3, 2.1, and 2.9 mJ fluence for two and 10 passes, followed by H&E staining. Ex vivo skin tissue sections treated with a PSL at 2.9 mJ fluence for 10 passes were also immunostained for Melan-A and CD31. RESULTS: Intraepidermal vacuoles were observed, along with pigment accumulation and inflammatory cell infiltration in the vacuoles at 24 hours after PSL treatment in the in vivo skin specimens. The vacuoles expanded as the fluence increased. Numerous intraepidermal vacuoles were observed, with dermal hemorrhage and inflammatory cell infiltration upon high-fluence, multi-pass PSL treatment in the in vivo skin specimens. PSL treatment yielded both epidermal and dermal vacuoles in ex vivo skin specimens. Melan-A-positive cells were seen in the cystic wall of vacuoles in the epidermal basal layer, whereas CD31-positive cells were detected in the cystic wall of some dermal vacuoles. CONCLUSIONS: The fractionated 1064-nm PSL produced epidermal vacuoles and dermal lesions, with histological differences between the in vivo and ex vivo skin specimens. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

The DNA replication regulator MCM6: An emerging cancer biomarker and target.

MCM6 is a significant DNA replication regulator that plays a crucial role in sustaining the cell cycle. In many cancer cells, MCM6 expression is enhanced. For example, persistently increased expression of MCM6 promotes the formation, development and progression of hepatocellular carcinoma (HCC). Up- and down-regulation studies have indicated that MCM6 regulates cell cycle, proliferation, metastasis, immune response and the maintenance of the DNA replication system. MCM6 can also regulate downstream signaling such as MEK/ERK thus promoting carcinogenesis. Accordingly, MCM6 may represent a sensitive and specific biomarker to predict adverse progression and poor outcome. Furthermore, inhibition of MCM6 may be an effective cancer treatment. The present review summarizes the latest results on the inactivating and activating functions of MCM6, underlining its function in carcinogenesis. Further studies of the carcinogenic functions of MCM6 may provide novel insight into cancer biology and shed light on new approaches for cancer diagnosis and treatment.

Postoperative Onset and Detection of SARS-CoV-2 in Surgically Resected Specimens From Gastrointestinal Cancer Patients With Pre/Asymptomatic COVID-19.

OBJECTIVE: To describe the epidemiologic features and clinical courses of gastrointestinal cancer patients with pre/asymptomatic COVID-19 and to explore evidence of SARS-CoV-2 in the surgically resected specimens. SUMMARY BACKGROUND DATA: The advisory of postponing or canceling elective surgeries escalated a worldwide debate regarding the safety and feasibility of performing elective surgical procedures during this pandemic. Limited data are available on gastrointestinal cancer patients with pre/asymptomatic COVID-19 undergoing surgery. METHODS: Clinical data were retrospectively collected and analyzed. Surgically resected specimens of the cases with confirmed COVID-19 were obtained to detect the expression of ACE2 and the presence of SARS-CoV-2. RESULTS: A total of 52 patients (male, 34) with a median age 62.5 years were enrolled. All the patients presented no respiratory symptoms or abnormalities on chest computed tomography before surgery. Six patients (11.5%) experienced symptom onset and were confirmed to be COVID-19. All were identified to be preoperatively pre/asymptomatic, as 5 were with SARS-CoV-2 presenting in cytoplasm of enterocytes or macrophages from the colorectal tissues and 1 had symptom onset immediately after surgery. The case fatality rate in patients with COVID-19 was 16.7%, much higher than those without COVID-19 (2.2%). CONCLUSIONS: Gastrointestinal cancer patients with pre/asymptomatic COVID-19 were at high risk of postoperative onset and death. At current pandemic, elective surgery should be postponed or canceled. It highlights the need for investigating the full clinical spectrum and natural history of this infection. The early colorectal tropism of SARS-CoV-2 may have major implications on prevention, diagnosis, and treatment of COVID-19.