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Ting Deng, Yin Lin, Li Chen, Jun-Ying Jiang Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Jun-Ying Jiang, Email 1057851146@qq.comObjective: To compare the spontaneous pregnancy rates between dydrogesterone and Gonadotropin-releasing hormone agonist (GnRH-a) treatments in patients with endometriosis stage III and IV after laparoscopy.Methods: The clinical data of patients with endometriosis stage III and IV administered laparoscopic surgery in our hospital from January 2018 to March 2020 were retrospectively analyzed. Totally 151 cases were divided into two groups according to postoperative medication, including the study (70 cases) and control (81 cases) groups treated with dydrogesterone and GnRH-a, respectively. The spontaneous pregnancy and subsequent pregnancy outcomes were assessed within 12 months.Results: Totally 49 patients had spontaneous pregnancy. Among them, there were 31 cases in the dydrogesterone group (spontaneous pregnancy rate of 44.3%, 31/70), including 25 live birth cases (35.7%, 25/70), 4 miscarriage cases, and 2 ectopic pregnancy cases. The time to conception was 1– 10 months (median value of 5 months). Totally 18 cases in the GnRH-a group had spontaneous pregnancy (22.2%, 18/81), including 16 live birth cases (19.8%, 16/81). 81) and 2 miscarriage cases; the time to conception was 3– 11 months (median value of 6 months). There were significant differences in spontaneous pregnancy rate and cumulative spontaneous pregnancy rate between the two groups (P = 0.005 and 0.003, respectively).Conclusion: Dydrogesterone after laparoscopic surgery in patients with endometriosis stage III and IV improved the natural pregnancy rate.Keywords: endometriosis, laparoscopic surgery, dydrogesterone, gonadotropin-releasing hormone agonist, spontaneous pregnancy

Genomic signatures like k-mers have become one of the most prominent approaches to describe genomic data. As a result, myriad real-world applications, such as the construction of de Bruijn graphs in genome assembly, have been benefited by recognizing genomic signatures. In other words, an efficient approach of genomic signature profiling is an essential need for tackling high-throughput sequencing reads. However, most of the existing approaches only recognize fixed-size k-mers while many research studies have shown the importance of considering variable-length k-mers.

Purpose: The reason for enhanced fracture healing in traumatic brain injury patients is not clearly understood. It is possible that factors inherent in the brain passing through the blood-brain barrier to the peripheral circulation, or a disruption of central nervous system (CNS) control of the sympathetic nervous system (SNS), stimulates the process of fracture healing.Methods: In this study, we assessed proliferation [using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay] and differentiation [using alkaline phosphatase (ALP)] in rat osteoblasts incubated with gray matter or other tissue extracts with and without the addition of an α- or β-adrenergic receptor blocker (phentolamine or propranolol).Results: Gray matter extract from normal brain caused a dose-dependent increase in osteoblast proliferation and differentiation. Serum from normal rats enhanced differentiation but not proliferation. Alpha-receptor blockade had no effect on proliferation or differentiation. Beta-receptor blockade caused a partial, but statistically significant, decrease in gray matter stimulation of osteoblast differentiation.Conclusion: The results of this study indicate that gray matter extract from normal brain increases osteoblast proliferation and differentiation and that β receptors may be involved in differentiation under these conditions. [ABSTRACT FROM AUTHOR]

The objective of this study was to detect cerebral potentials elicited by proximal stimulation of the first sacral (S1) nerve root at the S1 dorsal foramen and to investigate latency and amplitude of the first cerebral potential. Tibial nerve SEP and S1 nerve root SEP were obtained from 20 healthy subjects and 5 patients with unilateral sciatic nerve or tibial nerve injury. Stimulation of the S1 nerve root was performed by a needle electrode via the S1 dorsal foramen. Cerebral potentials were recorded twice to document reproducibility. Latencies and amplitudes of the first cerebral potentials were recorded. Reproducible cerebral evoked potentials were recorded and P20s were identified in 36 of 40 limbs in the healthy subjects. The mean latency of P20 was 19.8 ± 1.6 ms. The mean amplitude of P20-N30 was 1.2 ± 0.9 μV. In the five patients, P40 of tibial nerve SEP was absent, while well-defined cerebral potentials of S1 nerve root SEP were recorded and P20 was identified from the involved side. This method may be useful in detecting S1 nerve root lesion and other disorders affecting the proximal portions of somatosensory pathway. Combined with tibial nerve SEP, it may provide useful information for diagnosis of lesions affecting the peripheral nerve versus the central portion of somatosensory pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although poor control of hypertension is a problem worldwide, most published studies of adherence to antihypertensive medications have involved only white subjects. Objective: This study examined levels of and factors associated with short-term adherence to beta-blocker therapy among a representative sample of ethnic Chinese patients with hypertension from a large territory in Hong Kong. METHODS: Data for all hypertensive patients aged > or = 18 years who received a prescription for a beta-blocker at a visit to any public primary care clinic in the New Territory East cluster of Hong Kong and made at least 1 subsequent visit for a refill of this prescription between January 2004 and June 2007 were obtained from a validated clinical database generalizable to the Chinese population. The proportion of patients who were adherent to beta-blocker therapy was measured based on the medication possession ratio (MPR), calculated over 2 consecutive visits. Good adherence was defined as an MPR > or = 80%. Factors potentially associated with adherence to beta-blockers were investigated using multivariable logistic regression analysis, with adjustment for age, sex, payment status, service type, district of residence, visit type, and number of comorbidities. RESULTS: Data were obtained for 15,918 eligible patients (62.2% female; mean age, 59.1 years). Of these patients, 81.3% were adherent to beta-blocker therapy. Factors associated with a greater likelihood of good adherence to beta-blocker therapy were age > or = 50 years (adjusted odds ratio [AOR], age 50-59 years = 1.53 [95% CI, 1.38-1.70]; AOR, age 60-69 years = 1.85 [95% CI, 1.64-2.10]; AOR, age > or = 70 years = 1.88 [95% CI, 1.66-2.12]; all, P < 0.001); fee paid versus fee waived (AOR = 1.16 [95% CI, 1.06-1.28]; P = 0.001); attendance at a family medicine specialist clinic (AOR = 1.30 [95% CI, 1.09-1.54]; P = 0.003); and follow-up visit versus new-patient visit (AOR = 2.67 [95% CI, 2.42-2.95]; P < 0.001). CONCLUSION: Among these Chinese patients with hypertension, younger patients, those whose fees were waived, and those who were newly prescribed a beta-blocker had a greater likelihood of being nonadherent. [ABSTRACT FROM AUTHOR]

Background: Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.Methods: Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients' demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes).Results: 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients' demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age > or = 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension.Conclusion: The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients. [ABSTRACT FROM AUTHOR]

Background: There is a scarcity of studies addressing the factors associated with impaired fasting glucose in Chinese patients with uncomplicated hypertension. We included 1,218 patients newly prescribed a single antihypertensive drug in the public primary healthcare setting in Hong Kong, where their fasting glucose levels were measured 6--7 weeks after the first-ever antihypertensive prescription. Methods: The odds ratios of having above borderline (≥ 6.1 mmol/l) and adverse (≥ 7.0 mmol/l) glucose levels, respectively, were studied according to patient age, gender, socioeconomic status, clinic types and antihypertensive drug classes by multivariable regression analyses. Results: The fasting glucose levels were statistically similar (p = 0.786) among patients prescribed thiazide diuretics (5.48 mmol/l, 95%, 5.38, 5.59), calcium channel blockers (5.46 mmol/l, 95% C.I. 5.37, 5.54), β-blockers (5.42 mmol/l, 95% C.I. 5.34, 5.51) and drugs acting on the renin angiotensin system (RAS) [5.41 mmol/l, 95% C.I. 5.20, 5.61]. Multivariate analyses reported no significant associations between antihypertensive drug class and impaired fasting glucose. Elderly patients and male gender were significantly more likely to present with above borderline and adverse readings respectively. Conclusion: Clinicians should be aware of the increased risk of impaired fasting glucose in these groups, and use of thiazides should not in itself deter its use as a first-line antihypertensive agent among ethnic Chinese patients. [ABSTRACT FROM AUTHOR]

Objective: Expand genetic screening for atypical Type I sialidosis (ST-1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population., Methods: We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation., Results: A total of 31 patients from 23 unrelated families were genetically diagnosed with ST-1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951&#95;968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST-1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic-clonic seizures. Mobility and independence varied greatly across the cohort. Cherry-red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians., Interpretation: ST-1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry-red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

FARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1)., Methods: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a -/- ) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons., Results: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx., Conclusions: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization., Significance Statement: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission., (© 2024 European Pain Federation ‐ EFIC ®.)

Objective: To investigate the accuracy and efficiency of spine 2D/3D preoperative CT and intraoperative X-ray registration through a framework for spine 2D/3D single-vertebra navigation registration based on the fusion of dual-position image features. Methods: The preoperative CT and intraoperative anteroposterior (AP) and lateral (LAT) X-ray images of 140 lumbar spine patients who visited Huashan Hospital Affiliated to Fudan University from January 2020 to December 2023 were selected. In order to achieve rapid and high-precision single vertebra registration in clinical orthopedic surgery, a designed transformation parameter feature extraction module combined with a lightweight module of channel and spatial attention (CBAM) was used to accurately extract the local single vertebra image transformation information. Subsequently, the fusion regression module was used to complement the features of the anterior posterior (AP) and lateral (LAT) images to improve the accuracy of the registration parameter regression. Two 1×1 convolutions were used to reduce the parameter calculation amount, improve computational efficiency, and accelerate intraoperative registration time. Finally, the regression module outputed the final transformation parameters. Comparative experiments were conducted using traditional iterative methods (Opt-MI, Opt-NCC, Opt-C2F) and existing deep learning methods convolutional neural network (CNN) as control group. The registration accuracy (mRPD), registration time, and registration success rate were compared among the iterative methods. Results: Through experiments on real CT data, the image-guided registration accuracy of the proposed method was verified. The method achieved a registration accuracy of (0.81±0.41) mm in the mRPD metric, a rotational angle error of 0.57°±0.24°, and a translation error of (0.41±0.21) mm. Through experimental comparisons on mainstream models, the selected DenseNet alignment accuracy was significantly better than ResNet as well as VGG (both P <0.05). Compared to existing deep learning methods [mRPD: (2.97±0.99) mm, rotational angle error: 2.64°±0.54°, translation error: (2.15±0.41) mm, registration time: (0.03±0.05) seconds], the proposed method significantly improved registration accuracy (all P <0.05). The registration success rate reached 97%, with an average single registration time of only (0.04±0.02) seconds. Compared to traditional iterative methods [mRPD: (0.78±0.26) mm, rotational angle error: 0.84°±0.57°, translation error: (1.05±0.28) mm, registration time: (35.5±10.5) seconds], registration efficiency of the proposed method was significantly improved (all P <0.05). The dual-position study also compensated for the limitations in the single-view perspective, and significantly outperforms both the front and side single-view perspectives in terms of positional transformation parameter errors (both P <0.05). Conclusion: Compared to existing methods, the proposed CT and X-ray registration method significantly reduces registration time while maintaining high registration accuracy, achieving efficient and precise single vertebra registration.

Per/polyfluoroalkyl substances (PFASs) are ubiquitous, bioaccumulative, and recalcitrant contaminants, posing global exposure and health risks. The effects of chemical structures on toxicities and the mechanisms of their obesogenic effects were largely unclear. This study used the model organism Caenorhabditis elegans to assess the impact of long-term exposure to different PFASs (PFNA, PFOSA, PFBS, PFHxS, 6:2 FTS, 4:2 FTS, PFOA, and PFOS) on growth and lipid metabolism and discussed the obesogenic mechanisms of selected PFASs. The growth assays indicated longer carbon-fluorine (-CF) chains and total fluorine atoms increased developmental toxicity of PFASs, while at 8 -CF chain-length, PFNA (-COOH terminal), PFOS (-SO 3 terminal), and PFOSA (-SO 2 NH 2 terminal) exhibited differential growth inhibition. With the toxicity ranking of PFNA > PFOS > PFOSA, all PFASs significantly induced total lipid accumulation and perturbed the lipid composition in C. elegans. All three PFASs significantly induced lipogenesis gene expression and partially suppressed lipolysis genes. The results suggested that the disruption of lipid metabolism of PFOSA depends on sbp-1, while PFNA and PFOS depend on nhr-49. In conclusion, long-term exposure to PFNA, PFOSA, and PFOS triggers obesogenic effects in organisms by distinct molecular mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glycosaminoglycans (GAGs) are extensively utilized in clinical, cosmetic, and healthcare field, as well as in the treatment of thrombosis, osteoarthritis, rheumatism, and cancer. The biological production of GAGs is a strategy that has garnered significant attention due to its numerous advantages over traditional preparation methods. In this review, we embark on a journey to decode the intricate molecular symphony that orchestrates the biosynthesis of glycosaminoglycans. By unraveling the complex interplay of related enzymes and thorough excavation of the intricate metabolic cascades involved, GAGs chain aggregation and transportation, which efficiently and controllably modulate GAGs sulfation patterns involved in biosynthetic pathway, we endeavor to offer a thorough comprehension of how these remarkable GAGs are intricately assembled and pushes the boundaries of our understanding in GAGs biosynthesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Despite rapid advances in liquid biopsy for circulating tumor DNA (ctDNA), its prognostic value for venous thromboembolism (VTE) in patients with cancer is underexplored, particularly in underserved and minoritized populations., Methods: We analyzed data from 1,038 cancer patients who underwent ctDNA measurement for oncologic care at a large safety-net hospital system in the US. We investigated the association between ctDNA and VTE after adjusting for cancer type, stage, treatment, and time from initial diagnosis using Fine-Gray models. We further assessed the discrimination of the genetic, clinical-only, and combined models using the area under the time-dependent receiver operating characteristic curve (AUC)., Results: The presence of pathogenic ctDNA was independently associated with VTE after adjusting for clinical variables. Independent of tumor type, the number of pathogenic ctDNA mutations was predictive of future VTE risk (adjusted subdistribution hazard ratio 2.75, 1.94, and 1.38 for ≥3, 2, and 1 pathogenic mutation, respectively, compared to none; p<0.0001). The association was primarily driven by mutations in KRAS, PTEN, CDKN2A, NF1, and EGFR genes. Compared to the clinical-only model (AUC 0.71, 95% CI 0.64-0.76), the combined clinical and ctDNA model had a numerically higher time-dependent AUC (AUC 0.74, 95% CI 0.67-0.80)., Conclusions: CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management., (Copyright © 2024 International Society on Thrombosis and Haemostasis. All rights reserved.)

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2, and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency., (Copyright © 2024 Copyright: © The Author(s)(2024).)

Background: Equinovarus deformity correction was performed by soft tissue release and bone deformity correction, and tendon transfer to maintain deformity correction. Because of the high complication rate of tendon fixation methods, partial or total anterior tibial tendon or posterior tibial tendon transfer to the peroneus tertius tendon was reported. The purpose of this study was (i) to review the results of this tendon transfer technique after release and correction of talipes equinovarus, and (ii) to analyze the complication of this technique., Methods: Between February 2017 and May 2022, 176 patients (210 feet) with equinus and/or varus foot and ankle deformities underwent anterior or posterior tibial tendon transfer to the peroneus tertius in our institute. Preoperative and postoperative foot and ankle range of motion (passive and active) were checked. The postoperative radiographic assessment included antero-posterior (AP), lateral, and hindfoot alignment radiographs. Preoperative and postoperative lateral tibio-talar, talo-calcaneal, talo-first metatarsal, tibial-sole angles, hindfoot alignment, and anterior subluxation of the talus were checked. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and visual analog scale (VAS) were used to assess pain. Paired Student's t-test was used to compare the clinical scores and radiographic angles before the operation and at the last follow-up., Results: The mean age of the patients was 23.27 ± 13.44 years (range, 3-69 years). The mean follow-up time was 25.56 ± 16.37 months (range, 12-68 months). There were significant differences between the preoperative and postoperative measurements of the lateral tibio-talar angle, lateral talo-calcaneal angle, lateral talo-first metatarsal angle, lateral tibial-sole angle, and hindfoot alignment (p < 0.001). There was significant difference between the preoperative and postoperative AOFAS and VAS scores (p < 0.001). The early complications included infection in one patient, skin necrosis in two patients, and plantar numbness in three patients. The late complications included pin infection in three patients, tibio-talar joint compression in four patients, forefoot pain in two patients, toe flexion in two patients, and plantar numbness in one patient. There were three cases of complications (1.43%) related to the transferred tendons., Conclusion: Tibialis anterior or posterior tendon transfer to the peroneus tertius is a safe and effective method for equinovarus deformity correction. It yielded excellent outcomes that produced high patient satisfaction and few complications., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Objective: This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS)., Methods: Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway., Results: We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt ( p  < 0.05), JAK2 and STAT3 (JAK2: p  < 0.05; STAT3: p  < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene., Conclusion: Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.

Hyaluronidases catalyze the degradation of hyaluronan (HA), which is finding rising applications in medicine, cosmetic, and food industries. Recombinant expression of hyaluronidases in microbial hosts has been given special attention as a sustainable way to substitute animal tissue-derived hyaluronidases. In this study, we focused on optimizing the secretion of hyaluronidase from Homo sapiens in Pichia pastoris by secretion pathway engineering. The recombinant hyaluronidase was first expressed under the control of a constitutive promoter P GCW14 . Then, two endoplasmic reticulum-related secretory pathways were engineered to improve the secretion capability of the recombinant strain. Signal peptide optimization suggested redirecting the protein into co-translational translocation using the ost1-proα signal sequence improved the secretion level by 20%. Enhancing the co-translational translocation by overexpressing signal recognition particle components further enhanced the secretory capability by 48%. Then, activating the unfolded protein response by overexpressing a transcriptional factor ScHac1p led to a secreted hyaluronidase activity of 4.06 U/mL, which was 2.1-fold higher than the original strain. Finally, fed-batch fermentation elevated the production to 19.82 U/mL. The combined engineering strategy described here could be applied to enhance the secretion capability of other proteins in yeast hosts. KEY POINTS: • Improving protein secretion by enhancing co-translational translocation in P. pastoris was reported for the first time. • Overexpressing Hac1p homologous from different origins improved the rhPH-20 secretion. • A 4.9-fold increase in rhPH-20 secretion was achieved after fermentation optimization and fed-batch fermentation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the effectiveness and maintenance of perceptional learning (PL) on vision improvement in keratoconus (KC) patients corrected with spectacles., Design: Randomized, double-blind clinical trial., Methods: Non-progressive KC patients 9 years of age or older who had best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and who were contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat principle., Results: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs 0.02 ± 0.06 logMAR; P = .0006). Eight of 17 (47.06%) patients in the PL group reached CDVA improvement ≥2 lines (P = .0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs 0.01 ± 0.07 logMAR; P = .0011). The increase in CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = .009). No side effects were observed, and no subjects withdrew from the study because of training difficulties., Conclusions: Three-month PL improved vision in KC patients, and the improvement was maintained after 3 months of treatment cessation. The results indicate that PL may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Nail unit squamous cell carcinoma (nSCC) is a malignant subungual tumour. Although it has a low risk of metastasis and mortality, the tumour has a significant local recurrence rate. There is insufficient data to determine whether functional surgery is less effective than amputation for nSCC that does not involve the bone. Objectives We aimed to investigate existing data on the outcomes of functional surgery and amputation for nSCC without bone invasion. Materials and Methods We carried out an extensive search in PubMed, Embase, Cochrane Library, Web of Science, and Scopus for appropriate English-language academic papers, starting with the creation of individual resources until February 23, 2023. The main outcome was local recurrence. Initially, 2191 studies related to nSCC were selected. Information from every research study was retrieved and subdivided, comprising the year of publication, period, number of patients, age, gender distribution, tumour stage, type of intervention, number of recurrences, and follow-up period. Results Ten independent studies (319 lesions) were finally selected. Mohs micrographic surgery was the most reported surgical modality, followed by wide surgical excision and amputation. Local recurrence rates between Mohs micrographic surgery, wide surgical excision and amputation treatment were nearly identical. Other surgical methods included limited surgical excision, partial ablation, and limited excision until the clearing of margins, with recurrence rates up to 50%. Conclusions Given the functional impairment and psychological distress associated with phalanx amputation, functional surgery, including Mohs micrographic surgery and wide surgical excision , should be the preferred therapy for nSCC without bone involvement. Amputation should remain the preferred therapy for nSCC that involves the bone. Partial excision should be avoided. Further studies on whether Mohs micrographic surgery or wide surgical excision is a better option for nSCC not involving the bone are required.

Objectives: To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore its mechanisms via the PI3K/AKT signaling pathway, aiming to provide a basis for the clinical application of melatonin., Methods: Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group, an HIBD group, and a melatonin group ( n =9 each). The neonatal rat HIBD model was established using the classic Rice-Vannucci method. Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining. Autophagy-related protein levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunofluorescence staining and Western blot analysis. Phosphorylated phosphoinositide 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) protein expression levels were measured by immunohistochemistry and Western blot. The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis., Results: Twenty-four hours post-modeling, neurons in the sham operation group displayed normal size and orderly arrangement. In contrast, neurons in the HIBD group showed swelling and disorderly arrangement, while those in the melatonin group had relatively normal morphology and more orderly arrangement. Nissl bodies were normal in the sham operation group but distorted in the HIBD group; however, they remained relatively intact in the melatonin group. The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group, but was reduced in the melatonin group compared to the HIBD group ( P <0.05). The number of p-PI3K + and p-AKT + cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group ( P <0.05). LC3 and Beclin-1 protein expression levels were higher, and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group ( P <0.05); however, in the melatonin group, LC3 and Beclin-1 levels decreased, and p-PI3K and p-AKT increased compared to the HIBD group ( P <0.05). The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K + and p-AKT + cells between the two groups ( P <0.05)., Conclusions: Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD, thereby alleviating HIBD. This mechanism is associated with the PI3K/AKT pathway.

Hidradenitis suppurativa (HS) is an inflammatory follicular dermatological condition that typically affects the intertriginous and anogenital regions of the apocrine gland-bearing skin. The management of this chronic and recurring disease necessitates a combination of lifestyle changes, medication, and surgical approaches to achieve the best possible outcomes. While medical treatments are recommended for this multimodal disease, surgical therapy, which is the gold standard of treatment for HS, has proven to be the most effective treatment because it provides long-lasting local disease control, reduces the recurrence of lesions, and ensures complete healing of lesions. In the last decade, there has been exponential growth in research into various surgical techniques and reconstructive care, enabling patients to have more surgical options. There is a wide range of surgical management procedures available, such as incision and drainage, deroofing, excisional surgery, carbon dioxide laser therapy, and skin tissue-sparing excision with electrosurgical peeling. Among these surgical procedures, wide surgical excision is the best option since it can eradicate all the affected lesions. Meanwhile, the preferred approach to reconstruction at various anatomical locations remains debatable. Here, we review a variety of surgical treatments and reconstructive techniques for HS, particularly various flap techniques for the axillary, gluteal, and inframammary regions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT)., Objectives: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality., Methods: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We assessed associations with mortality using Cox regression., Results: Among 15 342 patients with an incident cancer diagnosis from 2011 to 2020, we identified 298 with isolated SpVT. Patients with hepatocellular carcinoma (HCC) and SpVT (n = 146) had the highest disease prevalence (20%), lowest rate of AC treatment (2%), and similar rate of usual-site VTE (4.2%) vs those without SpVT (5.2%) at 6 months, though tumor thrombus vs bland was associated with worse overall survival. In patients with non-HCC bland SpVT (n = 114), AC (n = 37) was more common in those with non-upper gastrointestinal cancers and fewer comorbidities. AC was associated with more recanalization (44% vs 15%, P = .041) but no differences in usual-site VTE, MB/CRNMB, or mortality at 6 months., Conclusion: Cancer-associated isolated SpVT is a common but heterogeneous thrombotic disease that is treated differently from usual-site VTE. Tumor thrombus is a negative prognostic factor. Initiation of AC in bland thrombi requires judicious consideration of thrombotic and bleeding risk., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

A new lignan, named pouzolignan P ( 1 ), together with 14 known ones ( 2 - 15 ) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K ( 3 ), gnemontanins E ( 5 ), gnetuhainin I ( 6 ), and styraxlignolide D ( 15 ) showed excellent ACLY inhibitory effect with IC 50 values of 9.06, 0.59, 2.63, and 7.62 μM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use., Methods: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE&gt;=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC&gt;=0.39x10(9) cells/L., Results: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up., Conclusion: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

Objective: This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A (RVA) in the Pearl River Delta region of Guangdong Province, China., Methods: This study included individuals aged 28 days-85 years. A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens, including RVA, using a Gastrointestinal Pathogen Panel, followed by genotyping, virus isolation, and complete sequencing to assess the genetic diversity of RVA., Results: The overall RVA infection rate was 14.59% (103/706), with an irregular epidemiological pattern. The proportion of co-infection with RVA and other pathogens was 39.81% (41/103). Acute gastroenteritis is highly prevalent in young children aged 0-1 year, and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea. G9P[8] (58.25%, 60/103) was found to be the predominant genotype in the RVA strains, and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis. Recombination analysis showed that gene reassortment events, selection pressure, codon usage bias, gene polymorphism, and post-translational modifications (PTMs) occurred in the G9P[8] and G3P[8] strains., Conclusion: This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China, further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity. Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients., Methods: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector., Results: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon)., Conclusions: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)