Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification.

BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification. METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated ß-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways. RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model. CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

Ligand-to-Ligand Interactions That Direct Formation of D2-Symmetrical Alternating Circular Helicate.

This work demonstrates that ligand-to-ligand interactions between achiral bis-ß-diketonate (BTP) and chiral bis(4-phenyl-2-oxazolinyl)pyridine [( R)- or ( S)-Ph-Pybox] are successfully directed to the fabrication of a D2-symmetrical alternating circular helicate with the general formula [( R)- or ( S)-Ph-Pybox]4(LnIII)4(BTP)6. The lanthanide(III) LnIII assemblies (LnIII4- RRRR and LnIII4- SSSS) have a nanometer-size squarelike grid (interatomic distances > 10 Å). X-ray structure analysis revealed that the circular helicate contains two double helicate LnIII2L2 units, where both show ( M)-helicity for LnIII4- RRRR and ( P)-helicity for LnIII4- SSSS, where π-π stacking interaction is present between the side arm of ( R)-Ph-Pybox (Ph1) and the adjacent BTP ligand around the EuIII metal center ( dππ = 3.636 Å: the diketonate plane···Ph1 distance). The newly obtained circular lanthanide(III) helicate exists as single and homochiral diastereomers in solution (LnIII4- RRRR and LnIII4- SSSS), exhibiting circularly dichroism (CD) and circularly polarized luminescence (CPL). Conversely, the circular helicate favors the heterochiral arrangement (i.e., LnIII4- RRRR/LnIII4- SSSS).

Elevated production of IL-36α in chronic hepatitis B virus-infected patients correlates with viral load.

Chronic hepatitis B (CHB) infection is a typical inflammatory disease characterized by a dysregulated expression of cytokines, which contributes to the pathogenesis of chronic Hepatitis B virus (HBV) infection. IL-36 cytokines (IL-36α, IL-36ß, IL-36γ and IL-36Ra) are important players in infection and immunity. However, their roles in the pathogenesis of chronic HBV infection remain unknown. Here the circulating concentrations of IL-36 cytokines from 50 CHB patients and 30 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Sera concentrations of IL-36α were found to be significantly elevated in CHB patients, while the concentrations of IL-36ß, IL-36γ and IL-36Ra were not significantly different in comparison to healthy donors. Furthermore, increased IL-36α concentrations correlated positively with HBV-DNA levels in CHB patients. Our study suggests that IL-36α production was up-regulated during CHB infection, which could be directly related to HBV-DNA loads in CHB patients. The immunoregulatory role of IL-36α in the pathogenesis of chronic HBV infection should be further studied.

Eruptive disseminated Spitz naevus (EDSN) in a young girl of Indian origin.

Eruptive disseminated Spitz naevus (EDSN) is a rare entity and has never been documented in a South-east Asian individual (of Indian origin) previously. We report an adolescent with this condition which, to our knowledge, has only been previously reported a few times.

Benzene homologues in environmental matrixes from a pesticide chemical region in China: Occurrence, health risk and management.

The contamination status and health risks of benzene, toluene, ethylbenzene and xylene (BTEX) in air, soil, dust and groundwater were evaluated in a pesticide chemical region located in Hebei province, China. The concentrations of BTEX in air ranged from 7.80 to 238ug/m(3) and those in soil and dust ranged from lower than limit of detection (LOD) to 32,360ng/g dw, and those in groundwater varied from 2.68 to 98.6ug/L. Generally, the levels of BTEX in multimedia matrixes were all below the standards established in China. Health risk assessment was performed based on the monitoring data via inhalation, dermal contact and ingestion pathways and hazard quotient (HQ) was calculated to be on the order of 10(-7), below 10(-6), and Hazard index (HI) levels of BTEX were lower than 1.0. However, both HQ and HI ascended with an increase in work experience/exposure. Integrated risk management was proposed to eliminate BTEX pollution and to protect occupational health of workers in those industries.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16 189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Prevalence of depression, anxiety in China during the COVID-19 pandemic: an updated systematic review and meta-analysis.

Background: Mental health risks associated with the aftermath of the COVID-19 pandemic are often overlooked by the public. The aim of this study was to investigate the effects of the COVID-19 pandemic on depression and anxiety disorders in China. Methods: Studies were analyzed and extracted in accordance with the PRISMA 2020 flowchart. The studies were screened and extracted using electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov according to the predefined eligibility criteria. The Cochrane Review Manager software 5.3.1 was used for data analysis and the risk of bias assessment. Results: As of 2023, a total of 9,212,751 Chinese have been diagnosed with COVID-19 infection. A total of 913,036 participants in 44 studies were selected following the eligibility criteria, the statistical information of which was collected for meta-analysis. The pooled prevalence of depression and anxiety were 0.31 (95% CI: 0.28, 0.35; I2 = 100.0%, p < 0.001) and 0.29 (95% CI: 0.23, 0.36; I2 = 100.0%, p < 0.001), respectively. After performing a subgroup analysis, the prevalence of depression among women, healthcare workers, students, and adolescents was 0.31 (95% CI: 0.22, 0.41), 0.33 (95% CI: 0.26, 0.44), 0.32 (95% CI: 0.26, 0.39), and 0.37 (95% CI: 0.31, 0.44), respectively. Conclusion: The prevalence of depression and anxiety among the Chinese was overall high. Monitoring and surveillance of the mental health status of the population during crises such as sudden global pandemics are imperative. Systematic review registration: https://clinicaltrials.gov/, identifier [CRD42023402190].

Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases.

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients.

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results.

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

Understanding the ligamentum teres of the hip: a histological study.

OBJECTIVE: To perform a histological study describing the microstructure of the ligamentum teres of the hip, with special emphasis on the presence of nerve bundles. Our study aims to correlate the microstructure of the ligamentum teres with its postulated functions, allowing greater understanding of its role within the hip joint. METHODS: Fresh specimens excised intra-operatively in 11 patients undergoing open hip procedures were preserved in formalin and sent to the laboratory for histological analysis by our collaborating pathologist. The specimens were sectioned and stained, and examined under the microscope to look at their microstructure. In addition, a novel staining technique was employed to detect neural elements within the individual specimens . RESULTS: The ligamentum teres is composed predominantly of a connective tissue matrix of collagen fibers, fibrous and adipose tissue, with an overlying layer of investing synovium. In addition, there are blood vessels of various sizes surrounded by a layer of encircling fat. In all specimens examined, there were nerve bundles of various shapes and sizes, regardless of the age of the patient. CONCLUSION: The ligamentum teres has both mechanical and biological functions within the hip joint and should no longer be considered a developmental vestige. Where possible, any surgical procedures around the hip joint should aim to limit damage to this structure to minimize any potential loss of function. Level of Evidence Basic Science Study.

The value of computed tomography scan versus an explorative surgical approach for removal of squamous cell carcinoma of the posterior pharyngeal wall.

BACKGROUND: The prevertebral fascia plays a key role in surgery of posterior pharyngeal wall tumors. Invasion of the prevertebral muscles determines the irresectability of the tumor and accurate diagnosis of invasion posteriorly is a prerequisite for major ablative surgery. METHODS: A retrospective study was performed to define the value of CT scanning versus open neck exploration with regard to the resectability of posterior pharyngeal wall carcinoma. The predictive value of preoperative CT scans was assessed and compared with the outcome of open neck exploration and resectability of the primary tumor, using the final histopathology report as a gold standard. RESULTS: Nineteen patients with 20 tumors were included in this study. Overall the CT scan was correct concerning prevertebral muscle status in 4 out of 20 (20%), whereas open neck exploration was correct in 18 tumors (90%). CONCLUSION: The predictive value of a suspicious CT scan in determining prevertebral muscle invasion is extremely low in this study. Open neck exploration seems to be superior for determining resectability of posterior wall carcinoma.

A new problem-solving indwelling voice prosthesis, eliminating the need for frequent Candida- and "underpressure"-related replacements: Provox ActiValve.

OBJECTIVES: To develop and clinically assess a new prosthesis for voice rehabilitation after total laryngectomy that solves the problem of frequent Candida- and "underpressure"-related replacements. MATERIAL AND METHODS: We designed a voice prosthesis with a new valve mechanism, applying Candida-resistant fluoroplastic (Teflon-like) material for the valve and valve seat and magnets to generate an active closing force, preventing inadvertent opening of the valve during swallowing or deep inhalation. Several prototypes were tested in 13 laryngectomized patients and, subsequently, the final design was assessed in a prospective clinical trial in a cohort of 18 patients with a short device lifetime of their standard indwelling voice prosthesis (mean 30 days). RESULTS: Prototype testing and the long-term clinical trial confirmed that the new valve material remained free of Candida growth and that the use of magnets can prevent inadvertent opening of the valve during swallowing and/or deep inhalation. This resulted in a highly significant increase in device lifetime in the 18 laryngectomized patients in the prospective trial (14-fold increase on average, range 3-39-fold; p < 0.001). Lubrication with special medical-grade fluoridated silicone oil is favorable in patients who experience possible adhesion of the valve to the valve seat. CONCLUSIONS: This new voice prosthesis, the Provox ActiValve, represents a solution for patients who have the problem of requiring very frequent voice prosthesis replacements due to excessive Candida growth and/or inadvertent opening of the valve by swallowing and inhalation-related underpressure in the esophagus.

Lower mortality from nasopharyngeal cancer in The Netherlands since 1970 with differential incidence trends in histopathology.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is rare in western countries albeit affected by common and unrelated phenomena: smoking less in men, more in women and immigration from China and North Africa. We studied trends in NPC incidence, tumour morphology, survival and mortality in order to assess progress against this cancer. MATERIALS AND METHODS: A trend analysis was performed with nationwide incidence and survival data (from The Netherlands Cancer registry in 1989-2009), followed by analysis of mortality (data from Statistics Netherlands) covering the period 1970-2009, and calculating estimated percentages of change (EAPC) in both. According to the WHO classification we distinguished keratinizing SCC (WHO-I), differentiated (WHO-IIA) and undifferentiated (WHO-IIB) non-keratinizing carcinoma. RESULTS: NPC incidence significantly decreased since 1989, especially in males (EAPC 1989-2009: -1.3; 95% CI: -2.5, -0.2) and in patients with keratinizing SCC (WHO-I) (EAPC: -3.6; 95% CI: -5.3, -1.8). By contrast, the incidence of differentiated non-keratinizing tumours (WHO-IIA) significantly increased in the same period (EAPC: 9.6; 95% CI: 5.6, 13.5). One- and three-year relative survival, as an indicator of disease-specific survival increased slightly from 79% to 81% and from 57% to 65% since 1989. NPC mortality significantly decreased since 1970 (EAPC: -1.2; 95% CI: -1.8, -0.5) and more pronounced since 1989 (EAPC: -3.0; 95% CI: -4.3, -1.6). CONCLUSION: During the past two decades, the incidence of NPC in The Netherlands decreased mainly by less keratinizing, supposedly smoking-related NPC (WHO-I). However, the incidence of non-keratinizing NPC (WHO-IIA, B) increased, most likely due to EBV infection and thus related to higher immigration levels of people from high-incidence areas.

Understanding the ligamentum teres of the hip: a histological study

Objective: To perform a histological study describing the microstructure of the ligamentum teres of the hip, with special emphasis on the presence of nerve bundles. Our study aims to correlate the microstructure of the ligamentum teres with its postulated functions, allowing greater understanding of its role within the hip joint. Methods: Fresh specimens excised intra-operatively in 11 patients undergoing open hip procedures were preserved in formalin and sent to the laboratory for histological analysis by our collaborating pathologist. The specimens were sectioned and stained, and examined under the microscope to look at their microstructure. In addition, a novel staining technique was employed to detect neural elements within the individual specimens . Results: The ligamentum teres is composed predominantly of a connective tissue matrix of collagen fibers, fibrous and adipose tissue, with an overlying layer of investing synovium. In addition, there are blood vessels of various sizes surrounded by a layer of encircling fat. In all specimens examined, there were nerve bundles of various shapes and sizes, regardless of the age of the patient. Conclusion: The ligamentum teres has both mechanical and biological functions within the hip joint and should no longer be considered a developmental vestige. Where possible, any surgical procedures around the hip joint should aim to limit damage to this structure to minimize any potential loss of function. Level of Evidence Basic Science Study.