Advances in immunology of male reproductive toxicity induced by common environmental pollutants.

Humans are exposed to an ever-increasing number of environmental toxicants, some of which have gradually been identified as major risk factors for male reproductive health, even associated with male infertility. Male infertility is usually due to the reproductive system damage, which may be influenced by the exposure to contaminants such as heavy metals, plasticizers, along with genetics and lifestyle. Testicular immune microenvironment (TIM) is important in maintaining normal physiological functions of the testis, whether disturbed TIM after exposure to environmental toxicants could induce reproductive toxicity remains to be explored. Therefore, the current review aims to contribute to the further understanding of exposure and male infertility by characterizing environmental exposures and the effect on TIM. We first summarized the male reproductive toxicity phenotypes induced by common environmental pollutants. Contaminants including heavy metals and plastic additives and fine particulate matter (PM2.5), have been repetitively associated with male infertility, whereas emerging contaminants such as perfluoroalkyl substances and micro(nano)plastics have also been found to disrupt TIM and lead to male reproductive toxicity. We further reviewed the importance of TIM and its homeostasis in maintaining the normal physiological functions of the testis. Most importantly, we discussed the advances in immunology of male reproductive toxicity induced by metals and metalloids, plastic additives, persistent organic pollutants (POPs), micro(nano)plastic and PM2.5 to suggest the importance of reproductive immunotoxicology in the future study of environmental toxicants, but also contribute to the development of effective prevention and treatment strategies for mitigating adverse effects of environmental pollutants on human health.

Enabling the design of surgical instruments for under-resourced patients through metal additive manufacturing: ulnar shortening osteotomy as an example.

BACKGROUND: Ulnar shortening osteotomy (USO) has demonstrated good outcomes for patients with ulnar impaction syndrome. To minimize complications such as non-union, precise osteotomy and firm fixation are warranted. Despite various ulnar shortening systems have been developed, current technology does not meet all needs. A considerable portion of patients could not afford those designated USO systems. To tackle this challenge, our team reported successful results in standardized free-hand predrilled USO technique. However, it is still technical demanding and requires sufficient experience and confidence to excel. Therefore, our team designed an ulnar shortening system based on our free-hand technique principle, using metal additive manufacturing technology. The goal of this study is to describe the development process and report the performance of the system. METHODS: Utilizing metal additive manufacturing technology, our team developed an ulnar shortening system that requires minimal exposure, facilitates precise cutting, and allows for the easy placement of a 3.5 mm dynamic compression plate, available to patients at zero out-of-pocket cost. For performance testing, two surgeons with different levels of experience in ulnar shortening procedures were included: one fellow-trained hand and wrist surgeon and one senior resident. They performed ulnar shortening osteotomy (USO) using both the free-hand technique and the USO system-assisted technique on ulna sawbones, repeating each method three times. The recorded parameters included time-to-complete-osteotomy, total procedure time, chip diameter, shortening length, maximum residual gap, and deviation angle. RESULTS: For the hand and wrist fellow, with the USO system, the time-to-complete osteotomy was significantly reduced. (468.7 ± 63.6 to 260.0 ± 5 s, p < 0.05). Despite the preop goal was shortening 3 mm, the average shortening length was significantly larger in the free-hand group (5 ± 0.1; 3.2 ± 0.2 mm, p < 0.05). Both maximum residual gap and deviation angle reported no statistical difference between the two techniques for the hand surgeon. As for the senior resident, the maximum residual gap was significantly reduced, using the USO system (2.9 ± 0.8; 0.4 ± 0.4 mm, p = 0.02). Between two surgeons, significant larger maximum residual gap and deviation angle were noted on the senior resident doctor, in the free-hand technique group, but not in the USO system group. CONCLUSION: The developed USO system may serve as a valuable tool, aiding in reliable and precise cutting as well as fixation for patients undergoing ulnar shortening osteotomy with a 3.5 mm dynamic compression plate, even for less experienced surgeons. The entire process, from concept generation and sketching to creating the CAD file and final production, serves as a translatable reference for other surgical scenarios.

Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

Arthroscopic debridement, synovectomy, and thermal shrinkage for basal joint arthritis.

BACKGROUND: Ligamentous laxity, cartilage wear, and diffuse synovitis are frequently seen in thumb basal joint arthritis. Although these degenerative changes may be mild for the majority, they have the potential to cause discomfort during movement and compromised hand function. This study assesses the long-term outcomes of arthroscopic debridement, synovectomy, and thermal shrinkage in managing early-stage basal joint arthritis. METHODS: We retrospectively reviewed patients with basal joint arthritis who underwent arthroscopic debridement, synovectomy, and thermal shrinkage between November 2010 and January 2021 by a single surgeon at our medical institute. We assessed functional outcomes, thumb range of motion, perioperative nonsteroidal anti-inflammatory drug (NSAID) use, return to work and satisfaction level. RESULTS: A total of 12 patients (13 hands), with a mean follow-up of 72 months, were included in this study. Significant improvements were observed in pain scores and functional outcomes, along with a reduction in postoperative NSAID use. Patients also reported a relatively quick return to work and a high satisfaction level. CONCLUSION: The study highlights the benefits of arthroscopic intervention, providing a minimally invasive approach with favorable long-term outcomes for patients with symptomatic basal joint arthritis.

Research and Development of a 3D-Printed Dynamic Finger Flexion Orthosis for Finger Extension Stiffness-A Preliminary Study.

Finger extension stiffness is a common post-traumatic complication that results in the hand's functional impairment. In clinical practice, a dynamic splint enables the patient to stretch the affected finger independently. However, current dynamic splints have drawbacks, such as limited stretching efficacy, and interfere with the hand's functional activities. Therefore, this study aimed to develop a dynamic finger flexion orthosis capable of stretching each finger joint using additive manufacturing (AM) technology, thereby enabling hand functional activity, and analyze the clinical improvement in the range of motion (ROM). One subject with a hand fracture was recruited while undergoing a 7-week home-based rehabilitation program for the orthosis. The outcome measurements included the total active motion (TAM), the tip-to-finger distance (TPD), and the score on the Disability of Arm, Shoulder, and Hand (DASH) questionnaire. The results show that the TAM of the participant's fingers increased by 72.7 degrees on average, the TPD decreased by 3.5 cm on average, and the DASH score decreased to 9.5 points. The 7-week home-based rehabilitation program for the orthosis resulted in a 53.6% increase in the TAM on average. The developed orthosis improved hand function and enabled a more complete ROM in finger flexion.

Arsenic exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

Arsenic (As) is a notorious environmental toxicant widely present in various natural environments. As exposure has been correlated with the decline in sperm motility. Yet, the mechanism has not been fully elucidated. Adult male C57 mice were given 0, 1, or 15 mg/L NaAsO2 for 10 weeks. The mature seminiferous tubules and sperm count were decreased in As-exposed mice. Sperm motility and several sperm motility parameters, including average path velocity (VAP), straight-line velocity (VSL), curvilinear velocity (VCL), beat-cross frequency (BCF), linearity (LIN), straightness (STR), and amplitude of lateral head displacement (ALH), were declined in As-exposed mice. RNA sequencing and transcriptomics analyses revealed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways. Untargeted metabolomics analyses indicated that energy metabolism was disrupted in As-exposed mouse testes. Gene set enrichment analysis showed that glycolysis and oxidative phosphorylation were disturbed in As-exposed mouse testes. As-induced disruption of testicular glucose metabolism and oxidative phosphorylation was further validated by RT-PCR and Western blotting. In conclusion, As exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

Ulnar carpal translation following palmar locking plate fixation for distal radius fractures: a retrospective analysis.

BACKGROUND: Concomitant injuries to the radiocarpal ligaments may occur during episodes of distal radius fractures, which may not cause acute subluxation or dislocation but can lead to radiocarpal instability and progress over time. This study aimed to analyze the occurrence of ulnar carpal translation (UCT) after open reduction and internal fixation of distal radius fractures and evaluate the associated factors of UCT. METHODS: The retrospective study has been done now and includes patients treated between 2010 and 2020 who had undergone reduction and locking plate fixation of distal radius fractures. We assessed radiographs taken immediately after the operation and at 3 months post-operation, enrolling patients with UCT for evaluation. In addition to demographic data, we evaluated radiographic parameters, including fracture pattern, fragment involvement, and ulnar variance. We also assessed the palmar tilt-lunate (PTL) angle to determine associated rotatory palmar subluxation of the lunate (RPSL). RESULTS: Among the 1,086 wrists, 53 (4.9%) had UCT within 3 months post-operation. The majority of wrists with UCT exhibited normal to minus ulnar variance (49 wrists; mean: -1.1 mm), and 24 patients (45.3%) had concomitant RPSL. Fracture classification was as follows: 19 type A3 (35.8%), 5 type C1 (9.4%), 11 type C2 (20.8%), and 18 type C3 (34.0%). Radial styloid was involved in 20 wrists (37.7%), palmar rim in 18 wrists (34.0%), dorsal rim in 25 wrists (47.2%), and die-punch fractures in 3 wrists (5.7%). Concomitant ulnar styloid fractures were present in 29 wrists (54.7%). CONCLUSION: This study highlights the potential for UCT to occur following reduction and fixation of distal radius fractures, particularly in cases with a more severe fracture pattern and combined with ulnar minus variance. The high incidence of concomitant RPSL provides further evidence for the possibility of associated radiocarpal ligament insufficiency after distal radius fracture.

Comparing the Outcomes of Suture Anchor Repair and Rein-Type Capsular Suture for Triangular Fibrocartilage Complex Foveal Tears With a Minimum 2-Year Follow-Up.

PURPOSE: Recent biomechanical studies have highlighted the importance of foveal reinsertion when repairing triangular fibrocartilage complex (TFCC) injury with foveal tears. However, clinical studies comparing different repair techniques are scarce. We compared the clinical outcomes of suture anchor repair and rein-type capsular suture in patients with TFCC palmer 1B foveal tears with a minimum of 2-year follow-up. METHODS: This was a single-surgeon, single-center, retrospective, comparative study. We included patients who underwent TFCC repair surgery due to a foveal tear from December 2013 to October 2018 with a minimum follow-up of 24 months. Postoperative Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score, visual analogue scale for pain, wrist range of motion, and grip strength were compared. We also measured the maximal ulnar head displacement with dynamic ultrasound to quantify distal radioulnar joint stability. RESULTS: In total, 103 patients were in the suture anchor group (group A) and 84 patients in the rein-type capsular suture group (group B). The mean follow-up time exceeded three years for both groups. There was a minimal difference regarding QuickDASH score, visual analogue scale for pain, and grip strength ratio between the two groups. The rein-type group had significantly better Modified Mayo Wrist Score. The suture anchor group showed better distal radioulnar joint stability with dynamic ultrasound, but was more limited in ulnar deviation. However, these differences are most likely clinically insignificant. CONCLUSIONS: Both suture anchor repair and rein-type capsular suture yielded satisfactory results for TFCC 1B foveal tear in a minimum of 2-year follow-up. The functional scores were similar, and no major complications or recurrent instability were noted in either group. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective Therapeutic Comparative Investigation IV.

Proliferation and Differentiation Potential of Bone Marrow-Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis.

This study compared the proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated ß-galactosidase (SA-ß-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-ß-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes (p16, p21, and p53) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of SOD1, SOD2, and SOD3 compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes (SOX9, COL2, and COL10) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further in vivo investigation.

FUNDC1-mediated mitophagy triggered by mitochondrial ROS is partially involved in 1-nitropyrene-evoked placental progesterone synthesis inhibition and intrauterine growth retardation in mice.

Intrauterine growth retardation (IUGR) is a major cause of perinatal morbidity and mortality. Previous studies showed that 1-nitropyrene (1-NP), an atmospheric pollutant, induces placental dysfunction and IUGR, but the exact mechanisms remain uncertain. In this research, we aimed to explore the role of mitophagy on 1-NP-evoked placental progesterone (P4) synthesis inhibition and IUGR in a mouse model. As expected, P4 levels were decreased in 1-NP-exposed mouse placentas and maternal sera. Progesterone synthases, CYP11A1 and 3ßHSD1, were correspondingly declined in 1-NP-exposed mouse placentas and JEG-3 cells. Mitophagy, as determined by LC3B-II elevation and TOM20 reduction, was evoked in 1-NP-exposed JEG-3 cells. Mdivi-1, a specific mitophagy inhibitor, relieved 1-NP-evoked downregulation of progesterone synthases in JEG-3 cells. Additional experiments showed that ULK1/FUNDC1 signaling was activated in 1-NP-exposed JEG-3 cells. ULK1 inhibitor or FUNDC1-targeted siRNA blocked 1-NP-induced mitophagy and progesterone synthase downregulation in JEG-3 cells. Further analysis found that mitochondrial reactive oxygen species (ROS) were increased and GCN2 was activated in 1-NP-exposed JEG-3 cells. GCN2iB, a selective GCN2 inhibitor, and MitoQ, a mitochondria-targeted antioxidant, attenuated GCN2 activation, FUNDC1-mediated mitophagy, and downregulation of progesterone synthases in JEG-3 cells. In vivo, gestational MitoQ supplement alleviated 1-NP-evoked reduction of placental P4 synthesis and IUGR. These results suggest that FUNDC1-mediated mitophagy triggered by mitochondrial ROS may contribute partially to 1-NP-induced placental P4 synthesis inhibition and IUGR.

Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer.

Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.

Dual Parallel Intramedullary K-Wires for Arthrodesis of the Finger Distal or Thumb Interphalangeal Joints.

OBJECTIVE: K-wire arthrodesis methods are commonly used during arthrodesis of the finger distal interphalangeal (DIP) or thumb interphalangeal (IP) joints. Here we propose an advantageous approach involving dual parallel intramedullary K-wires with the K-wire tips cut to bury underneath the skin. METHODS: From January 2017 to December 2021, 35 patients (43 joints) underwent finger DIP or thumb IP joint arthrodesis using this method. Radiographic outcomes were evaluated, while functional outcomes were assessed using the visual analogue scale (VAS) for pain and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Patients with at least 1 year follow-up were analyzed. The preoperative and postoperative functional results were analyzed using the paired t-test. RESULTS: Arthrodesis union was achieved in 41/43 joints (95.3%). We treated 10 thumb IP joints and 33 finger DIP joints, for which the underlying cause was osteoarthritis and trauma in 37 and six digits, respectively. The average time of K-wire removal was 8.9 (range, 7-10) weeks after surgery. Twenty-four patients (27 joints; 22 women, two men) had at least 1 year follow-up (mean 15.9; range, 12.5-40.8) months. For patients with bone healing, the VAS score improved from 6.6 (range, 5-8) to 0.6 (range, 0-1) (p < 0.001), and the QuickDASH score improved from 57.9 (range, 31.8-77.3) to 14.7 (range, 6.8-20.5) (p < 0.001) at final follow-up. Both of the two failure cases were in the thumb. There were no other complications. CONCLUSIONS: This technique is simple and cost-effective and achieves a good union rate. The advantages include the ability to choose variable K-wire sizes according to the size of the medullary canal and the ease of postoperative care.

Outcomes of radiocarpal pinning to facilitate nerve repair in wrist-level ulnar nerve injuries with defect.

BACKGROUND: The ideal scenario for ulnar nerve repair is primary end-to-end neurorrhaphy in a tension-free environment. However, this could be complicated by soft tissue loss, scarring, and neuroma formation in a delayed injury, creating a nerve defect. With a wrist-level nerve defect, a flexion position can help shorten the nerve gap; however, maintaining the position can be challenging intraoperatively and postoperatively. METHODS: Previously, we proposed our method of using a 1.6-mm K wire for radius-lunate-capitate pinning of the wrist in flexion to minimize the nerve gap, thereby facilitating neuroma excision and end-to-end neurorrhaphy in delayed ulnar nerve injury. In this study, we elaborate our method and present our case series. RESULTS: From October 2018 to July 2020, five patients (mean age: 48.2 years; mean delay from injury to surgery: 84.6 days; mean follow-up: 17.5 months) were retrospectively reviewed. The mean flexion fixation angle was 52°, and the K wire was removed at an average of 5.1 weeks postoperatively. All patients were followed up for a minimum of 12 months. All patients achieved M4 and S3 or S3+ neurologically (according to the criteria of the Nerve Injuries Committee of the British Medical Research Council). The mean disabilities arm, shoulder, and hand score was 14.1. The mean grasp and pinch strengths were, respectively, 76.8% and 63.6% of the contralateral hand. All wrist range of motion returned to normal within 12 weeks. No complications were noted intraoperatively or postoperatively. CONCLUSION: Our study showed that radiocarpal pinning of the wrist in flexion was safe and convenient to minimize the nerve gap and to facilitate end-to-end neurorrhaphy in limited-sized wrist-level ulnar nerve defects.

Innovative Approach to Unicondylar Proximal Phalangeal Fracture Fixation: Combining Antegrade Intramedullary Pinning With Flexion Proximal Interphalangeal Joint Transfixation.

Various surgical techniques have been described for the fixation of displaced unicondylar fractures of the proximal phalanx, with K-wire and interfragmentary screws being the most commonly used. Although open reduction with joint exposure can provide direct visualization and allow for anatomic reduction, its potential drawbacks, such as joint stiffness and loss of range of motion, are of significant concern. We introduced a novel fixation technique for displaced unicondylar fractures of the proximal phalanx using antegrade intramedullary pinning and transfixation of the proximal interphalangeal joint, which is simple, effective, and does not require open reduction.

Phthalate exposure with sperm quality among healthy Chinese male adults: The role of sperm cellular function.

Adverse male reproduction caused by phthalate ester (PAE) exposure has been well documented in vivo. However, existing evidence from population studies remains inadequate to demonstrate the impact of PAE exposure on spermatogenesis and underlying mechanisms. Our present study aimed to explore the potential link between PAE exposure and sperm quality and the possible mediation by sperm mitochondrial and telomere in healthy male adults recruited from the Hubei Province Human Sperm Bank, China. Nine PAEs were determined in one pooled urine sample prepared from multiple collections during the spermatogenesis period from the same participant. Sperm telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined in sperm samples. The sperm concentration and count per quartile increment in mixture concentrations were -4.10 million/mL (-7.12, -1.08) and -13.52% (-21.62%, -4.59%), respectively. We found one quartile increase in PAE mixture concentrations to be marginally associated with sperm mtDNAcn (ß = 0.09, 95% CI: -0.01, 0.19). Mediation analysis showed that sperm mtDNAcn significantly explained 24.6% and 32.5% of the relationships of mono-2-ethylhexyl phthalate (MEHP) with sperm concentration and sperm count (ß = -0.44 million/mL, 95% CI: -0.82, -0.08; ß = -1.35, 95% CI: -2.54, -0.26, respectively). Our study provided a novel insight into the mixed effect of PAEs on adverse semen quality and the potential mediation role of sperm mtDNAcn.

Long-term cadmium exposure induces chronic obstructive pulmonary disease-like lung lesions in a mouse model.

Accumulating evidences demonstrate that long-term exposure to atmospheric fine particles and air pollutants elevates the risk of chronic obstructive pulmonary disease (COPD). Cadmium (Cd) is one of the important toxic substances in atmospheric fine particles and air pollutants. In this study, we aimed to establish a mouse model to evaluate whether respiratory Cd exposure induces COPD-like lung injury. Adult male C57BL/6 mice were exposed to CdCl2 (10 mg/L, 4 h per day) by inhaling aerosol for either 10 weeks (short-term) or 6 months (long-term). The mean serum Cd concentration was 6.26 µg/L in Cd-exposed mice. Lung weight and coefficient were elevated in long-term Cd-exposed mice. Pathological scores and alveolar destructive indices were increased in long-term Cd-exposed mouse lungs. Mean linear intercept and airway wall thickness were accordingly elevated in Cd-exposed mice. Inflammatory cell infiltration was obvious and inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8, IL-10 and TGF-ß, were up-regulated in Cd-exposed mouse lungs. α-SMA, N-cadherin and vimentin, epithelial-mesenchymal transition markers, and extracellular matrix collagen deposition around small airway, determined by Masson's trichrome staining, were shown in Cd-exposed mouse lungs. COPD-characteristic lung function decline was observed in long-term Cd-exposed mice. These outcomes show that long-term respiratory exposure to Cd induces COPD-like lung lesions for the first time.

Mitoquinone protects against acetaminophen-induced liver injury in an FSP1-dependent and GPX4-independent manner.

Mitochondrial oxidative stress has been a crucial mediator in acetaminophen (APAP)-induced hepatotoxicity. MitoQ, an analog of coenzyme Q10, is targeted towards mitochondria and acts as a potent antioxidant. This study aimed to explore the effect of MitoQ on APAP-induced liver injury and its possible mechanisms. To investigate this, CD-1 mice and AML-12 cells were treated with APAP. Hepatic MDA and 4-HNE, two markers of lipid peroxidation (LPO), were elevated as early as 2 h after APAP. Oxidized lipids were rapidly upregulated in APAP-exposed AML-12 cells. Hepatocyte death and mitochondrial ultrastructure alterations were observed in APAP-induced acute liver injury. The in vitro experiments showed that mitochondrial membrane potentials and OXPHOS subunits were downregulated in APAP-exposed hepatocytes. MtROS and oxidized lipids were elevated in APAP-exposed hepatocytes. We discovered that APAP-induced hepatocyte death and liver injury were ameliorated by attenuation of protein nitration and LPO in MitoQ-pretreated mice. Mechanistically, knockdown of GPX4, a key enzyme for LPO defense systems, exacerbated APAP-induced oxidized lipids, but did not influence the protective effect of MitoQ on APAP-induced LPO and hepatocyte death. Whereas knockdown of FSP1, another key enzyme for LPO defense systems, had little effect on APAP-induced lipid oxidation but partially weakened the protection of MitoQ on APAP-induced LPO and hepatocyte death. These results suggest that MitoQ may alleviate APAP-evoked hepatotoxicity by eliminating protein nitration and suppressing hepatic LPO. MitoQ prevents APAP-induced liver injury partially dependent of FSP1 and independent of GPX4.

Lateral Approach for Scaphoid Excision and Capitolunate Arthrodesis in the Treatment of Scapholunate Advanced Collapse and Scaphoid Nonunion Advanced Collapse Wrists: A Case Series.

OBJECTIVE: The dorsal approach is commonly used in open wrist arthrodesis. However, the extensor compartments and the dorsal wrist capsule need to be opened. We propose and evaluate a lateral approach using a small incision over the scaphoid anatomical snuffbox, which could be more straightforward for performing scaphoid excision and capitolunate arthrodesis in the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC). METHODS: Between 2016 and 2021, 10 patients were enrolled retrospectively and underwent the lateral approach for scaphoid excision and capitolunate arthrodesis. We presented the radiographic outcomes, including fusion status, capitolunate angle, and carpal height ratio. The functional outcomes of wrist range of motion, grip strength, visual analog scale (VAS) score for pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and Mayo wrist score were evaluated. The data obtained were analyzed and presented as the mean and standard deviation (SD). RESULTS: All 10 patients achieved solid bone fusion, and the mean follow-up period was 20.4 (range 12-38; SD 10.1) months. Postoperatively, the mean capitolunate angle and carpal height ratio improved from 18.1° (range 8-34°; SD 8.6°) to 2.9° (range 0-5°; SD 1.9°) and 0.45 (range 0.40-0.49; SD 0.03)% to 0.50 (range 0.46-0.54; SD 0.02)%, respectively. The average preoperative and final follow-up functional results were as follows: flexion-extension arc of 76.5° (range 50-110°; SD 20.0°) and 74.0° (range 65-90°; SD 9.1°); VAS pain score of 5.8 (range 4-7; SD 1.0) and 0.9 (range 0-2; SD 0.6); QuickDASH score of 55.9 (range 40.9-79.5; SD 11.4) and 26.1 (range 18.2-36.4; SD 6.0); and Mayo wrist score of 46.5 (range 25-60; SD 13.8) and 72.5 (range 70-80; SD 3.5), respectively. CONCLUSIONS: The lateral approach for scaphoid excision and capitolunate arthrodesis in treating SLAC and SNAC can provide a straightforward way for performance. This approach does not require disruption of the dorsal wrist capsule and extensor retinaculum. Bony healing can be achieved, and functional outcomes can be improved.

Outcomes of Percutaneous Pinning for Interfragmentary Fixation in Treating Bennett Fractures With Tiny Avulsion Fragments.

For Bennett fractures with tiny avulsion fragments, healing may be jeopardized owing to limited fracture contact surface if displacement of reduced fracture junctions occurs. This study aimed to assess the efficacy of treating Bennett fractures with tiny avulsion fragments using percutaneous small-diameter K-wires for tiny fragment fixation and thumb carpometacarpal (CMC) joint transfixation. From 2011 to 2019, we retrospectively enrolled patients with Gedda type 3 Bennett fractures who underwent operation with K-wire percutaneous pinning for the tiny fragment and CMC joint. We enrolled a total of 13 patients (13 fractures) with a mean age of 26.9 years (range, 18-42 years) at operation and a mean follow-up time of 17.9 months (range, 12-34 months). At the final follow-up, the shortened Disabilities of the Arm, Shoulder and Hand Questionnaire mean score was 4.7, and the visual analog scale score for pain during activity was 0.7. Mean grip strength was 34.7 kg (97.7% of the value on the unaffected side). Mean pinch strength was 5.4 kg (90.5% of the value on the unaffected side). Mean first web opening angle was 66.2° (96.6% of the value on the unaffected side). There were no changes in gap and step-off during the healing process and no osteoarthritic changes in the thumb CMC joint at the final follow-up. For Bennett fractures with tiny avulsion fragment, percutaneous treatment with small-diameter K-wires for fragment fixation and thumb CMC joint transfixation provides a viable alternative with fracture healing and good functional outcomes. [Orthopedics. 2023;46(2):103-107.].

Mitochondrial ROS-mediated ribosome stalling and GCN2 activation are partially involved in 1-nitropyrene-induced steroidogenic inhibition in testes.

In the past 50 years, testosterone (T) level in men has declined gradually. In this research, we discovered that acute exposure to 1-nitropyrene (1-NP), an environmental stressor from polluted atmosphere, reduced T contents by downregulating steroidogenic proteins in mouse testes and Leydig cells. Acute 1-NP exposure caused GCN2 activation and eIF2α phosphorylation, a marker of integrated stress, in mouse testes and Leydig cells. GCN2iB, a selective GCN2 kinase inhibitor, and siGCN2, the GCN2-targeted short interfering RNA, attenuated 1-NP-induced reduction of steroidogenic proteins in Leydig cells. Mechanistically, mitochondrial membrane potential was reduced and ATP5A, UQCRC2, SDHB and NDUFB8, four OXPHOS subunits, were reduced in 1-NP-exposed Leydig cells. Cellular mitochondrial respiration was inhibited and ATP production was reduced. Moreover, mitochondrial reactive oxygen species (ROS) were elevated in 1-NP-exposed Leydig cells. The interaction between GCN2 and uL10, a marker of ribosome stalling, was observed in 1-NP-exposed Leydig cells. MitoQ, a mitochondria-targeted antioxidant, attenuated1-NP-evoked ATP depletion and ribosome stalling in Leydig cells. Moreover, MitoQ suppressed 1-NP-caused GCN2 activation and eIF2α phosphorylation in Leydig cells. In addition, MitoQ alleviated 1-NP-induced steroidogenic inhibition in mouse testes. In conclusion, mitochondrial ROS-mediated ribosome stalling and GCN2 activation are partially involved in environmental stress-induced steroidogenic inhibition in testes.