Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.

SRSF9 promotes cell proliferation and migration of glioblastoma through enhancing CDK1 expression.

BACKGROUND: Glioblastoma (GBM) is a highly aggressive and prevalent brain tumor that poses significant challenges in treatment. SRSF9, an RNA-binding protein, is essential for cellular processes and implicated in cancer progression. Yet, its function and mechanism in GBM need clarification. METHODS: Bioinformatics analysis was performed to explore differential expression of SRSF9 in GBM and its prognostic relevance to glioma patients. SRSF9 and CDK1 expression in GBM cell lines and patients' tissues were quantified by RT-qPCR, Western blot or immunofluorescence assay. The role of SRSF9 in GBM cell proliferation and migration was assessed by MTT, Transwell and colony formation assays. Additionally, transcriptional regulation of CDK1 by SRSF9 was investigated using ChIP-PCR and dual-luciferase assays. RESULTS: The elevated SRSF9 expression correlates to GBM stages and poor survival of glioma patients. Through gain-of-function and loss-of-function strategies, SRSF9 was demonstrated to promote proliferation and migration of GBM cells. Bioinformatics analysis showed that SRSF9 has an impact on cell growth pathways including cell cycle checkpoints and E2F targets. Mechanistically, SRSF9 appears to bind to the promoter of CDK1 gene and increase its transcription level, thus promoting GBM cell proliferation. CONCLUSIONS: These findings uncover the cellular function of SRSF9 in GBM and highlight its therapeutic potential for GBM.

Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion.

BACKGROUND: For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC). AIM: To investigate the oncological profile of PLXDC1 in HCC. METHODS: Based on The Cancer Genome Atlas database, we analyzed the expression of PLXDC1 in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of PLXDC1 in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays. RESULTS: Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of PLXDC1 in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis. CONCLUSION: As a result of this study analyzing PLXDC1 from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Acod1/itaconate activates Nrf2 in pulmonary microvascular endothelial cells to protect against the obesity-induced pulmonary microvascular endotheliopathy.

BACKGROUND: Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear. METHODS: mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs. RESULTS: Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate. CONCLUSION: Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.

Monocytes release cystatin F dimer to associate with Aß and aggravate amyloid pathology and cognitive deficits in Alzheimer's disease.

BACKGROUND: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aß) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aß clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aß by monocytes in AD remains unclear. METHODS: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aß by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aß. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. RESULTS: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aß deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aß by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aß to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aß. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. CONCLUSIONS: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aß metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.

Jeotgalibacillus haloalkalitolerans sp. nov., a novel alkalitolerant and halotolerant bacterium, isolated from the confluence of the Fenhe River and the Yellow River.

A Gram-stain positive, aerobic, alkalitolerant and halotolerant bacterium, designated HH7-29 T, was isolated from the confluence of the Fenhe River and the Yellow River in Shanxi Province, PR China. Growth occurred at pH 6.0-12.0 (optimum, pH 8.0-8.5) and 15-40℃ (optimum, 32℃) with 0.5-24% NaCl (optimum, 2-9%). The predominant fatty acids (> 10.0%) were iso-C15:0 and anteiso-C15:0. The major menaquinones were MK-7 and MK-8. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that strain HH7-29 T was a member of the genus Jeotgalibacillus, exhibiting high sequence similarity to the 16S rRNA gene sequences of Jeotgalibacillus alkaliphilus JC303T (98.4%), Jeotgalibacillus salarius ASL-1 T (98.1%) and Jeotgalibacillus alimentarius YKJ-13 T (98.1%). The genomic DNA G + C content was 43.0%. Gene annotation showed that strain HH7-29 T had lower protein isoelectric points (pIs) and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt and alkali. The average nucleotide identity, digital DNA-DNA hybridization values, amino acid identity values, and percentage of conserved proteins values between strain HH7-29 T and its related species were 71.1-83.8%, 19.5-27.4%, 66.5-88.4% and 59.8-76.6%, respectively. Based on the analyses of phenotypic, chemotaxonomic, phylogenetic and genomic features, strain HH7-29 T represents a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus haloalkalitolerans sp. nov. is proposed. The type strain is HH7-29 T (= KCTC 43417 T = MCCC 1K07541T).

Thymic carcinoid with multiple bone metastases: A case report.

BACKGROUND: Thymic carcinoid (TC) is a rare entity among anterior mediastinal malignancies. TCs are neuroendocrine carcinomas that constitute approximately 2%-5% of all thymic epithelial tumors. CASE SUMMARY: The study reported a rare TC with multiple bone metastases. A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg. Magnetic resonance imaging scans revealed damage to the lumbar spine, sacrocaudal vertebrae and iliac crest, suggesting bone metastasis; computed tomography (CT) scan of the thorax showed a calcified anterior mediastinal mass; positron emission tomography-CT demonstrated multiple abnormal bone signals; and laboratory work-up showed no endocrine abnormalities. Fine-needle aspiration biopsy revealed predominantly single small, round to oval cells with scant cytoplasm and some loose clusters, suggesting endocrine manifestations. The pathological diagnosis was atypical carcinoid, which tend to originate from the thymus and was classified as intermediate-highly invasive. The patient underwent anlotinib-targeted therapy. Anlotinib (12 mg) was administered daily for 2 wk, after which the patient was allowed to rest for 21 d. Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29% after therapy. Treatment has a long stable disease benefit of more than 2.5 years. CONCLUSION: These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.

NIS-Promoted Chemodivergent and Diastereoselective Synthesis of Pyrrolinyl and Cyclopentenyl Spiropyrazolones via Regulated Cyclization of Alkylidene Pyrazolones with Enamino Esters.

An N-iodosuccinimide-promoted annulation of alkylidene pyrazolones with enamino esters has been explored to construct a spiropyrazolone moiety through a Michael addition/iodination/intramolecular nucleophilic substitution sequence. When the reaction was performed in acetonitrile at 100 °C, it furnished pyrrolinyl spiropyrazolones exclusively in an anti configuration through N-attacking cyclization. When the reaction was performed in dimethyl sulfoxide at 80 °C in the presence of K2HPO4, it afforded cyclopentenyl spiropyrazolones exclusively in the syn configuration through C-attacking cyclization. A plausible mechanism has also been proposed.

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

BACKGROUND: This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. METHODS: Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. RESULTS: The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). CONCLUSIONS: High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Testing the generalizability and effectiveness of deep learning models among clinics: sperm detection as a pilot study.

BACKGROUND: Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different sample preprocessing protocols, raising the concern over whether the reported accuracy of a deep learning model by one clinic could be reproduced in another clinic. Here we aim to investigate the effect of each imaging factor on the generalizability of object detection models, using sperm analysis as a pilot example. METHODS: Ablation studies were performed using state-of-the-art models for detecting human sperm to quantitatively assess how model precision (false-positive detection) and recall (missed detection) were affected by imaging magnification, imaging mode, and sample preprocessing protocols. The results led to the hypothesis that the richness of image acquisition conditions in a training dataset deterministically affects model generalizability. The hypothesis was tested by first enriching the training dataset with a wide range of imaging conditions, then validated through internal blind tests on new samples and external multi-center clinical validations. RESULTS: Ablation experiments revealed that removing subsets of data from the training dataset significantly reduced model precision. Removing raw sample images from the training dataset caused the largest drop in model precision, whereas removing 20x images caused the largest drop in model recall. by incorporating different imaging and sample preprocessing conditions into a rich training dataset, the model achieved an intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94-0.99) for precision, and an ICC of 0.97 (95% CI: 0.93-0.99) for recall. Multi-center clinical validation showed no significant differences in model precision or recall across different clinics and applications. CONCLUSIONS: The results validated the hypothesis that the richness of data in the training dataset is a key factor impacting model generalizability. These findings highlight the importance of diversity in a training dataset for model evaluation and suggest that future deep learning models in andrology and reproductive medicine should incorporate comprehensive feature sets for enhanced generalizability across clinics.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway.

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.

Effect of cytokines on advanced hepatocellular carcinoma prognosis receiving radiotherapy and tislelizumab plus anlotinib: a single-center phase II clinical trial.

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.

Posterior capsular radial sign: a novel method to confirm anterior vitreous cortex resection in phacovitrectomy.

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

Efficacy of Biomechanics-based Decompression Therapy in Managing Recurrent Diabetic Plantar Ulcers.

OBJECTIVE: The objective of this study is to assess the efficacy of decompression nursing based on biomechanical principles in managing recurrent diabetic plantar ulcers. METHODS: Sixty-seven patients experiencing recurrent diabetic plantar ulcers who sought medical attention at Huadong Hospital Affiliated to Fudan University between January 2021 and December 2022 were selected as participants for this study. The participants underwent biomechanics-based decompression nursing. We compared pre-intervention and post-intervention data to assess the differences in relevant observational indexes. RESULTS: Post-intervention, patients showed significant improvements in foot comfort scores and adherence to pressure reduction behavior compared with their pre-intervention status, with statistical significance (P < 0.05). The intervention was effective in 41 cases (61.19%), with 18 cases (26.87%) showing improvement and 8 cases (11.94%) deemed ineffective, culminating in an overall efficacy rate of 88.06%. All 67 patients achieved complete ulcer healing within an average duration of 58.63 ± 18.13 days, without any recorded recurrences. CONCLUSION: Biomechanics-based decompression nursing demonstrates effective facilitation of wound healing, yielding expeditious recovery, enhanced comfort, and a reduced incidence of recurrence.

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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. With the emergence of disease-modifying therapies, the prognosis of SMA has significantly improved, drawing increased attention to the importance of home rehabilitation and nursing management. Long-term, standardized home rehabilitation and nursing can delay the progression of SMA, enhance the psychological well-being, and improve the quality of life of both patients and caregivers. This article provides an overview of the goals of home rehabilitation, basic functional training methods, respiratory management, and nutritional management for SMA patients, as well as psychological health issues, emphasizing the significance of obtaining appropriate home rehabilitation and support during the care process.