Efficacy of ganglion impar block combined with pudendal nerve pulsed radiofrequency for pudendal neuralgia management-a randomized clinical trial.

BACKGROUND: Pudendal neuralgia is a chronic and debilitating condition. Its prevalence ranges from 5 to 26%. Currently, therapeutic approaches to treat pudendal neuralgia include patient education, medication management, psychological and physical therapy, and procedural interventions, such as nerve block, trigger point injections, and surgery. Drug therapy has a limited effect on pain relief. A pudendal nerve block may cause a significant decrease in pain scores for a short time; however, its efficacy significantly decreases over time. In contrast, pudendal nerve pulsed radiofrequency can provide pain relief for 3 months, and ganglion impar block has been widely used for treating chronic perineal pain and chronic coccygodynia. This study aimed to determine the efficacy and safety of monotherapy (pudendal nerve pulsed radiofrequency) and combination therapy (pudendal nerve pulsed radiofrequency plus ganglion impar block) in patients with pudendal neuralgia. METHODS: This randomized, controlled clinical trial will include 84 patients with pudendal neuralgia who failed to respond to drug or physical therapy. Patients will be randomly assigned into one of the two groups: mono or combined treatment groups. The primary outcome will be a change in pain intensity measured using the visual analog scale. The secondary outcomes will include a Self-Rating Anxiety Scale score, Self-Rating Depression Scale score, the use of oral analgesics, the Medical Outcomes Study Health Survey Short Form-36 Item score, and the occurrence of adverse effects. The study results will be analyzed using intention-to-treat and per-protocol analyses. Primary and secondary outcomes will be evaluated between the mono and combined treatment groups. Subgroup analyses will be conducted based on the initial ailment, age, and baseline pain intensity. The safety of the treatment will be assessed by monitoring adverse events, which will be compared between the two groups. DISCUSSION: This study protocol describes a randomized, controlled clinical trial to determine the efficacy and safety of mono and combination therapies in patients with pudendal neuralgia. The study results will provide valuable information on the potential benefits of this combination therapy and contribute to the development of more effective and safer treatments for patients with pudendal neuralgia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061800).

Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.

Changes in Corneal Epithelial Thickness in Different Areas After Femtosecond Laser-Assisted LASIK in Patients With High Astigmatism.

PURPOSE: To explore changes in corneal epithelial thickness (CET) after femtosecond laser-assisted laser in situ keratomileusis in patients with high astigmatism. METHODS: CET was measured at every intersection of the concentric circles and specific axes using AngioVue optical coherence tomography (Angio-OCT) preoperatively and 1 month postoperatively. The average thickness of corneal central, paracentral, and peripheral regions was the mean of the points within the central 2, 2 to 5, and 5 to 7 mm areas, respectively. Correlation analysis was performed to investigate the association between CET along different axes and other preoperative and postoperative parameters. RESULTS: Forty-two eyes of 28 patients were included. CET along the astigmatic (K1) and perpendicular (K2) axes in the central and paracentral areas increased (P < .001), whereas that along the K2 axis decreased in the peripheral area 1 month postoperatively (P = .001). The amount of CET change in the peripheral area between the K1 and K2 axes was significantly different (P < .001). In the central area, the change in CET along the K2 axis was positively correlated with ablation depth (r = 0.315, P = .042) and negatively with refractive power after surgery (r = -0.347, P = .024). In the peripheral area, the changes in CET along both K1 and K2 axes were negatively correlated with ablation depth (r = -0.431, P = .004; r = -0.387, P = .011, respectively). CONCLUSIONS: Epithelial modeling differed between the different astigmatism axes after refractive surgery. The compensatory response of the corneal epithelium is more pronounced along the steeper axis. [J Refract Surg. 2024;40(4):e239-e244.].

Structural and functional changes of binocular corneal innervation and ocular surface function after unilateral SMILE and tPRK.

AIMS: To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures. METHODS: 34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values. RESULTS: All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density. CONCLUSIONS: Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively.

Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP-RIPK1-NF-κB axis and influencing autophagy.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. METHODS: In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP-RIPK1-NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1ß and in the post-traumatic OA model. RESULTS: In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. CONCLUSIONS: These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.

Prognostic nomogram for predicting the overall survival rate of patients with uterine clear-cell carcinoma: Based on SEER database.

OBJECTIVE: To evaluate the risk factors for uterine clear-cell carcinoma (UCCC) and construct nomograms predicting 1-, 3-, and 5-year overall survival rates of patients with UCCC. METHODS: The demographic and clinical information of 1674 patients diagnosed with UCCC between 2004 and 2015, including age, race, marital status, tumor size, American Joint Committee on Cancer (AJCC) stage, and details of surgery and radiotherapy/chemotherapy, was collected from the Surveillance, Epidemiology, and End Results (SEER) database. After excluding patients with unknown AJCC stage, race, marital status, or lymph node information, 1469 patients remained. Risk factors were determined using univariate and multivariate analyses, and nomograms were developed to predict 1-, 3-, and 5-year overall survival of UCCC. Various indicators were used to evaluate the performance of the nomogram, such as the C-index, net classification improvement (NRI) and decision curve analysis (DCA). RESULTS: Age, log odds of positive lymph nodes, AJCC stage, surgery status, and chemotherapy status were independent risk factors for UCCC. The C-indexes of the training group and AJCC stage groups were 0.771 and 0.697, respectively. The results for the area under the receiver operating characteristics curve, NRI, and calibration curves indicated that the nomogram had good predictive ability. DCA revealed that the nomogram had greater clinical applicability than AJCC stage alone. Internal validation using the validation cohort also demonstrated that this nomogram had good predictive performance. CONCLUSION: A new nomogram comprising a combination of demographic and clinical characteristics provided better survival predictions than the AJCC staging system alone, which will facilitate prognostic assessments and clinical decision-making.

Spatial mapping of corneal biomechanical properties using wave-based optical coherence elastography.

Quantifying the mechanical properties of the cornea can provide valuable insights into the occurrence and progression of keratoconus, as well as the effectiveness of corneal crosslinking surgery. This study presents a non-contact and non-invasive wave-based optical coherence elastography system that utilizes air-pulse stimulation to create a two-dimensional map of corneal elasticity. Homogeneous and dual concentration phantoms were measured with the sampling of 25 × 25 points over a 6.6 × 6.6 mm2 area, to verify the measurement capability for elastic mapping and the spatial resolution (0.91 mm). The velocity of elastic waves distribution of porcine corneas before and after corneal crosslinking surgery were further mapped, showing a significant change in biomechanics in crosslinked region. This system features non-invasiveness and high resolution, holding great potential for application in ophthalmic clinics.

Appropriate addition power for aphakic infants determined by a smart wearable device Clouclip.

CLINICAL RELEVANCE: It is particularly important to perform reasonable and effective optical correction to enable visual development after primary lens removal surgery for congenital cataracts. Aphakic infants need a suitable addition power of prescription (ADD) to help them focus on close visual objects. BACKGROUND: It is challenging to obtain appropriate ADD power for infants due to poor cooperation and lack of subjective feedback. We aimed to determine the appropriate ADD for aphakic infants using a recently developed smart wearable device called Clouclip. METHODS: The study was a cross-sectional, observational pilot study. Twenty-three aphakic infants (aged from 6 months to 3.5 years) were invited to wear a smart wearable device for 7 days consecutively to monitor the near viewing distance in real life. Viewing habits and its associations with the possible influencing factors were investigated based on the data obtained from the device. RESULTS: The average proportion of near viewing time was 77.9% (95% confidence interval (CI) 72.1-83.7%). The average of the median near viewing distance was 23.8 cm (95% CI 20.6 cm-27.0 cm), which corresponded to an ADD of +4.25 D (95% CI + 3.75 D - +4.75 D) spectacle prescription. The height of the child was found to be positively correlated with the median of near viewing distance (r = 0.646, p = 0.001). Age, current ADD, age of cataract extraction surgery and bilaterality or monocularity of the aphakic eyes showed no significant correlation with the aforementioned viewing habits (all p > 0.05). CONCLUSION: By using the novel wearable device, we found the suitable ADD of spectacle prescription for aphakic infants is about +4.25 D. The height of the child was an influencing factor for ADD.

DMT1-mediated iron overload accelerates cartilage degeneration in Hemophilic Arthropathy through the mtDNA-cGAS-STING axis.

INTRODUCTION: Excess iron contributes to Hemophilic Arthropathy (HA) development. Divalent metal transporter 1 (DMT1) delivers iron into the cytoplasm, thus regulating iron homeostasis. OBJECTIVES: We aimed to investigate whether DMT1-mediated iron homeostasis is involved in bleeding-induced cartilage degeneration and the molecular mechanisms underlying iron overload-induced chondrocyte damage. METHODS: This study established an in vivo HA model by puncturing knee joints of coagulation factor VIII gene knockout mice with a needle, and mimicked iron overload conditions in vitro by treatment of Ferric ammonium citrate (FAC). RESULTS: We demonstrated that blood exposure caused iron overload and cartilage degeneration, as well as elevated expression of DMT1. Furthermore, DMT1 silencing alleviated blood-induced iron overload and cartilage degeneration. In hemophilic mice, articular cartilage degeneration was also suppressed by intro-articularly injection of DMT1 adeno-associated virus 9 (AAV9). Mechanistically, RNA-sequencing analysis indicated the association between iron overload and cGAS-STING pathway. Further, iron overload triggered mtDNA-cGAS-STING pathway activation, which could be effectively mitigated by DMT1 silencing. Additionally, we discovered that RU.521, a potent Cyclic GMP-AMP Synthase (cGAS) inhibitor, successfully suppressed the downward cascades of cGAS-STING, thereby protecting against chondrocyte damage. CONCLUSION: Taken together, DMT1-mediated iron overload promotes chondrocyte damage and murine HA development, and targeted DMT1 may provide therapeutic and preventive approaches in HA.

Truncated PD1 Engineered Gas-Producing Extracellular Vesicles for Ultrasound Imaging and Subsequent Degradation of PDL1 in Tumor Cells.

PDL1 blockade therapy holds great promise in cancer immunotherapy. Ultrasound imaging of PDL1 expression in the tumor is of great importance in predicting the therapeutic efficacy. As a proof-of-concept study, a novel ultrasound contrast agent has been innovated here to image and block PDL1 in the tumor tissue. Briefly, extracellular vesicles (EVs) are engineered to display truncated PD1 (tPD1) on the surface to bind PDL1 with high affinity by fusion to EV-abundant transmembrane protein PTGFRN. The engineered EVs are then encapsulated with Ca(HCO3)2 via electroporation and designated as Gp-EVtPD1, which would recognize PDL1 highly expressed cells and produce gas in the endosomes and lysosomes. On the one hand, the echogenic signal intensity correlates well with the PDL1 expression and immune response inhibition in the tumor. On the other hand, during the trajectory of Gp-EVtPD1 in the recipient cells, tPD1 on the EV binds PDL1 and triggers the PDL1 endocytosis and degradation in endosomes/lysosomes in a sequential manner, and thus boosts the anti-tumor immunity of cytotoxic T cells. In summary, Gp-EVtPD1 serves as a novel ultrasound contrast agent and blocker of PDL1, which might be of great advantage in imaging PDL1 expression and conquering immune checkpoint blocker resistance.

The Prevalence and Risk Factors of Blepharoptosis in an Elderly Asian Population.

BACKGROUND: Age-related blepharoptosis, or ptosis, affects vision and appearance. Associations with age, gender, BMI, and diabetes have been explored, but the link to blood lipids remains unclear. The impact on refraction also lacks consensus. This study addresses gaps by investigating ptosis prevalence and factors in a representative Chinese population, aiming for a comprehensive understanding. METHODS: A cross-sectional study was conducted among individuals aged 50 and above who were willing to participate in comprehensive systemic check-ups, behavioral questionnaires, and ophthalmic examinations at Yaoxi Community Health Center in Wenzhou City, Zhejiang Province. RESULTS: The prevalence of blepharoptosis among the elderly participants at this health center was 27.16%. Individuals with blepharoptosis tended to be older, male, exhibited slightly higher body mass index, wider waist circumference, engaged in lower exercise frequency, and had a higher prevalence of hypertension, diabetes, and with-the-rule astigmatism compared to their counterparts without these conditions. Adjusting for all other confounding variables, older age, being male, higher fasting plasma glucose (FPG), and lower exercise frequency displayed statistically significant relationships with blepharoptosis. After examining the distribution of blepharoptosis degrees within relevant factor subgroups, we noted a higher prevalence of severe ptosis in subgroups associated with older age, male gender, higher FPG, and against-the-rule astigmatism. CONCLUSION: The notable associations with age, gender, FPG, and exercise level suggest a multifactorial etiology for blepharoptosis. The observed link between with-the-rule astigmatism and blepharoptosis implies a potential contributory role in the refractive aspect of blepharoptosis. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy and Safety of Celiac Plexus Neurolysis Versus Splanchnic Nerve Neurolysis in the Management of Abdominal Cancer Pain: A Meta-analysis of 359 Patients.

BACKGROUND: Splanchnic nerve neurolysis (SNN) is commonly used as an alternative pain control technique to celiac plexus neurolysis (CPN) in patients with distortion of anatomy, but the analgesic effect and relative risks of the 2 procedures remain controversial in general condition. OBJECTIVES: The aim of this study was to evaluate the pain condition, safety, and symptom burden of SNN compared with CPN. STUDY DESIGN: A systematic review and meta-analysis of neurolysis therapy for intractable cancer-related abdominal pain. METHODS: A systematic search was performed for randomized controlled trials comparing SNN and CPN using the PubMed, Medline, Cochrane Library, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases. Meta-analysis was performed using Stata Version 15.0. Outcomes included pain condition, opioid consumption, adverse effects, quality of life (QOL), and survival rate. Standardized mean difference (SMD) was calculated for continuous outcomes with its corresponding 95% CI. LIMITATIONS: Study limitations include challenges to make subgroup analysis by intervention measures and addressing inevitable heterogeneity. Larger studies are needed for survival rates and further insights. RESULTS: Seven studies involving 359 patients were included. No significant difference was found in pain condition at 2 weeks [SMD = 0.75, 95% CI (-0.25, 1.74), P > 0.05], 2 months [SMD = 1.10, 95% CI (-0.21, 2.40), P > 0.05] and 6 months [SMD = 0.53, 95% CI (-0.02, 1.08), P > 0.05] between SNN and CPN. Opioid consumption was comparable at 2 weeks [SMD = 0.57, 95% CI (-1.21, 2.34), P > 0.05] and one month [SMD = 0.37, 95% CI (-1.33, 2.07), P > 0.05]. However, SNN was associated with a statistically significant reduction in the opioid consumption at 2 months postoperatively [SMD = 0.99, 95% CI (0.68, 1.30), P < 0.05]. A systematic review was performed for adverse effects and QOL. CONCLUSIONS: Our evidence supports that the analgesic effect of SNN is equivalent to that of CPN, independent of changes in the anatomical structure of the abdominal nerve plexus. SNN requires less use of opioids at 2 months and does not show greater improvement in pain burden compared to CPN.

Early versus delayed computed tomography-guided celiac plexus neurolysis for palliative pain management in patients with advanced pancreatic cancer: a retrospective cohort study.

Introduction: Abdominal and back pain is the most frequent symptom in patients with pancreatic cancer, with pain management being extremely challenging. This study aimed to evaluate pain control, opioid consumption, pain-interfered quality of life, and survival after early and delayed computed tomography (CT)-guided celiac plexus neurolysis (CPN). Methods: A retrospective analysis of pancreatic cancer patients receiving CPN for pain (n = 56) between June 2018 and June 2021 was done. The patients were grouped as early group (n = 22) and delayed group (n = 34) on the basis of the presence of persistent refractory pain according to expert consensus on refractory cancer pain. Results: Both groups were comparable in demographic characteristics and baseline pain conditions measured using the numeric rating scale (5.77 ± 1.23 vs. 6.27 ± 1.21; p = 0.141). The pain scores were significantly reduced in both groups; early CPN resulted in significantly lower scores from 3 to 5 months. The opioid consumption gradually decreased to a minimum at 2 weeks but increased at 1 month (35.56 ± 30.14 mg and 50.48 ± 47.90 mg, respectively); significantly larger consumption from 2 to 4 months was seen in the delayed group. The total pain interference was lower than baseline in all patients, with significant improvement after early CPN in sleep, appetite, enjoyment of life, and mood. The average survival time of the two groups was comparable. Conclusion: Early application of CT-guided CPN for patients with advanced pancreatic cancer may help reduce pain exacerbation and opioids consumption, without influencing the survival.

α 2 -ADRENORECEPTOR ANTAGONIST AMELIORATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY SUPPRESSING NOREPINEPHRINE-MEDIATED FIBROBLAST DIFFERENTIATION VIA INHIBITING PKC ACTIVATION.

ABSTRACT: Pulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α 2 -adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α 2A -AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. Reserpine and yohimbine alleviated pulmonary fibrosis in mice with sepsis by exhausting NE derived from the lung's adrenergic nerve and blocking α 2 -AR, respectively. There was no significant difference in the expression of the three α 1 -AR subtypes. The effect of NE on promoting pulmonary fibroblast differentiation in vitro was suppressed by yohimbine. Both the protein and mRNA expression levels of α 2A -AR were increased in pulmonary fibroblasts treated with LPS. Clonidine, a selective α 2 -AR agonist, enhanced LPS-induced differentiation in pulmonary fibroblasts, as indicated by the increase in α-smooth muscle actin and collagen I/III, which was mitigated by inhibiting PKC and p38. Further in vivo results indicated that yohimbine alleviated pulmonary fibrosis and inhibited the phosphorylation of PKC, p38, and Smad2/3 in lung tissue of mice exposed to LPS for 4 weeks. Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α 2 -AR. Blockage of α 2 -AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway.

CT-guided paravertebral injection of doxorubicin for treatment of postherpetic neuralgia: a database-based retrospective stratified study.

Objective: This study explored the impact of different doeses of doxorubicin in CT-guided transvertebral foraminal injections for postherpetic neuralgia (PHN) treatment and the impact of 0.5% doxorubicin treatment on patients with different disease courses and lesion locations. Methods: This retrospective study included 291 patients with PHN who received CT-guided doxorubicin injection at West China Hospital between April 2014 and February 2020. Results: A total of 228 patients received 0.5% doxorubicin treatment and 63 received 0.33% doxorubicin. Both groups showed significantly improvement in visual analogue scale (VAS) and Brief Pain Inventory (BPI) scores. The 0.5% doxorubicin group demonstrated significant lower VAS scores at 6 and 12 months after surgery (all p < 0.001) and a significant lower score on the BPI at 6 and 12 months than the 0.33% doxorubicin group (all p < 0.05). Stratified analysis of 0.5% doxorubicin demonstrated a significant reduction in VAS score at 1 week, 3 months, 6 months, and 12 months after treatment compared to baseline (all p < 0.05) and significant improvements in BPI score after treatment compared to baseline (p < 0.05). The VAS score of the chest group was significant higher than facial, neck and upper limbs and abdomen groupsin groups 1 week after surgery (all p < 0.05). Various aspects of quality of life, including daily life, enjoyment of life, sleep, relationships, work, walking ability, and emotions, significantly decreased after surgery (p < 0.05). Especially in sleep duration, there was an increase in patients reporting intermediate sleep (4-7 h) and a proportion achieving a normal sleep duration of ≥7 h. And no significant differences of BPI were observed among different affected locations. The incidence of adverse events in the 0.5% doxorubicin group and 0.33% doxorubicin group was 8.78 and 6.34%, respectively. Conclusion: CT-guided doxorubicin injection therapy has the potential to alleviate pain and enhance the quality of life in patients with PHN. Notably, the use of a 0.5% doxorubicin concentration yields more pronounced pain relief compared to a 0.33% concentration. While longer durations of PHN and specific affected sites may influence the response to treatment, the overall improvements in quality of life remain consistent.

Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.

Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.

Food waste anaerobic digestion plants: Underestimated air pollutants and control strategy.

Food waste management is an important global issue, and anaerobic digestion (AD) is a sustainable technology for treating food waste and developing a circular economy. Odor and health problems in AD plants have drawn increasing public attention. Therefore, this study investigated the odor characteristics and health risks in different workshops of food waste AD plants. At each site, the treatment capacities for kitchen and restaurant waste were 200 and 200-250 tons per day, respectively. Among the detected odorants, ethanol was the dominant component in terms of concentrations, while methanethiol, propanethiol, H2S, and acetaldehyde were the major odor contributors in different workshops. The odor contribution of propanethiol had been previously overlooked in several workshops. The unloading, pretreatment, and bio-hydrolysis workshops were identified as major areas requiring odor control. Besides odor, carcinogenic and non-carcinogenic risks commonly existed in food waste AD plants. The carcinogenic risk of acetaldehyde had been underestimated previously, and it was identified as the dominant carcinogen. Furthermore, benzene was a potential carcinogen. Non-carcinogenic risks were mainly caused by acetaldehyde, H2S, and ethyl acetate. The health risks were not always consistent with odor nuisance. Based on the odor and health risk assessments, several air pollution control strategies for food waste AD plants were proposed, including food waste source control, in-situ pollution control, and ex-situ pollution control.

The tibial tunnel drilling angles of 60° provided a lower ultimate load to failure on a single bundle posterior cruciate ligament graft using interference screw fixation compared to 30°/45°.

PURPOSE: To biomechanically compare the initial fixation strength of grafts among three tibial tunnel angles (30°/45°/60°) in transtibial posterior cruciate ligament (PCL) reconstruction. METHODS: A series of transtibial PCL reconstruction models were established with porcine tibias and bovine tendons. Specimens were randomly assigned to three groups according to the angles between the tibial tunnel and the perpendicular line of the tibial shaft: Group A (30°, n = 12), Group B (45°, n = 12), and Group C (60°, n = 12). The area of the tunnel entrance, the segmental bone mineral density (sBMD) of the graft fixation site of the tibia and the maximum insertion torque of the interference screw were measured. Finally, load to failure tests were carried out on the graft-screw-tibia constructs at the same rate. RESULTS: Ultimate load to failure in Group C (335.2 ± 107.5 N) was significantly lower than that in Group A (584.1 ± 127.9 N, P < 0.01) and Group B (521.9 ± 95.9 N, P < 0.01). There were no significant differences between biomechanical properties of Groups A and B (n.s.). The posterior part fractures of the tibial tunnel exit occurred in eight specimens of Group C. In addition, the ultimate load was proven to be related to insertion torque (rho = 0.7, P < 0.01), sBMD (rho = 0.7, P < 0.01), and the area of the tunnel entrance (rho =- 0.4, P = 0.01). CONCLUSION: The ultimate load to failure was significantly lower in tibial PCL interference screw fixation for tunnels drilled at 60° compared to 30°/45°. In addition, the ultimate load was significantly correlated with insertion torque, sBMD and the area of the tunnel entrance. Given that the load to failure of distal fixation may not be sufficient for early postoperative rehabilitation, a 60° tunnel should not be recommended to drill in tibia during PCL reconstruction.

Enhancement of 15% calcium oxide doped nano zero-valent iron on arsenic removal from high-arsenic acid wastewater.

Nano zero-valent iron (nZVI) has a great potential for arsenic removal, but it would form aggregates easily and consume largely by H+ in the strongly acidic solution. In this work, 15%CaO doped with nZVI (15%CaO-nZVI) was successfully synthesized from a simplified ball milling mixture combined with a hydrogen reduction method, which had a high adsorption capacity for As(V) removal from high-arsenic acid wastewater. More than 97% As(V) was removed by 15%CaO-nZVI under the optimum reaction conditions of pH 1.34, initial As(V) concentration 16.21 g/L, and molar ratio of Fe/As (nFe/nAs) 2.5:1. The effluent pH solution was weakly acidic 6.72, and the secondary arsenic removal treatment reduced the solid waste and improved arsenic grade in slag from the mass fraction of 20.02% to 29.07%. Multiple mechanisms including Ca2+ enhanced effect, adsorption, reduction, and co-precipitation coexisted for As(V) removal from high-arsenic acid wastewater. Doping of CaO might lead to improving cracking channels which was benefit for electronic transmission and the confusion of atomic distribution. The in situ weak alkaline environment generated on the surface of 15%CaO-nZVI would increase the content of γ-Fe2O3/Fe3O4, which was in favor for As(V) adsorption. In addition, H+ in the strongly acidic solution could accelerate corrosion of 15%CaO-nZVI and abundant fresh and reactive iron oxides continuously generated, which would provide plenty specific reactive site and fast charge transfer and ionic mobility for arsenic removal.