Preparation and Evaluation of Clarithromycin Taste-Masking Dry Suspension Using Hot Melt Extrusion Based on Solid Dispersion Technology.

Clarithromycin (CLA) is the preferred drug for treating respiratory infections in pediatric patients, but it has the drawbacks of extreme bitterness and poor water solubility. The purpose of this study was to improve solubility and mask the extreme bitterness of CLA. We use Hot Melt Extrusion (HME) to convert CLA and Eudragit® E100 into Solid Dispersion (SD). Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) were used to identify the crystalline form of the prepared SDs, which showed that the crystalline CLA was converted to an amorphous form. At the same time, an increase in dissolution rate was observed, which is one of the properties of SD. The results showed that the prepared SD significantly increased the dissolution rate of crystalline CLA. Subsequently, the SD of CLA was prepared into a dry suspension with excellent suspending properties and a taste-masking effect. The bitterness bubble chart and taste radar chart showed that the SD achieved the bitter taste masking of CLA. Principal components analysis (PCA) of the data generated by the electronic tongue showed that the bitter taste of CLA was significantly suppressed using the polymer Eudragit® E100. Subsequently, a dry suspension was prepared from the SD of CLA. In conclusion, this work illustrated the importance of HME for preparing amorphous SD of CLA, which can solve the problems of bitterness-masking and poor solubility. It is also significant for the development of compliant pediatric formulations.

Recurrent COVID-19-related psychotic disorder with neuro-immuno-endocrine dysfunction as a possible underlying mechanism: A case report from China.

Background: SARS-CoV-2, first identified in Wuhan, China, in December 2019, has been gradually spreading worldwide since 2020. The relationship between SARS-CoV-2 infection and psychotic disorders has received much attention, and several studies have described the direct/indirect mechanisms of its effects on the brain, but no mechanism has been found to explain recurrent episodes of COVID-19-related psychotic symptoms. Case: We report the case of an 18-year-old female patient with no family or personal psychotic disorder history with multiple hospital admissions with symptoms such as disorganized speech and behavior, hyperactivity, restlessness, and impulsive aggression during the COVID-19 recovery period. Relevant tests revealed longitudinal changes such as persistent IL-6 and IL-10 elevation, abnormal discharges on EEG, and brain and hippocampal MRI abnormal signals. The patient was treated with antipsychotics, MECT, combination therapy of hormones and antivirals, then discharged after multiple treatment rounds. Conclusion: The case presented here outlines the possibility that the COVID-19 recovery period may be a critical period for acute psychotic episodes and that the patient's recurrent psychotic symptoms may be associated with neuro-immuno-endocrine dysfunction mediated by sustained cytokine synthesis, further causing structural and functional brain damage. Routine psychiatric evaluation and related screening should be performed at all stages of the illness to better identify, prevent, and effectively intervene in psychiatric disorders following COVID-19. Because many outcomes require long-term assessment, a clearer understanding of the impact of the COVID-19 epidemic on mental health is likely to emerge in the future.

CCDC189 depletion leads to oligo-astheno-teratozoospermia and male infertility in mice.

In male reproductive system, proteins containing the coiled-coil domain (CCDC) are predominantly expressed in specific regions including the testis, epididymis, seminal vesicle, and prostate. They play a vital role in centriole formation, sperm motility and flagellar development in male gametes. Despite being highly expressed in the testis, the exact physiological function of the coiled-coil domain-containing 189 (Ccdc189) gene remain largely unclear. Our research provides a comprehensive and detailed investigation into the localization of CCDC189 protein within the testis seminiferous tubules. CCDC189 specifically expressed in spermatocytes, round spermatids and elongating spermatids in mouse testis. The deletion of Ccdc189 in mouse leads to male infertility, characterized by significantly reduced sperm counts and motility. Abnormally shaped spermatozoa with irregular tails, exhibiting shortened and twisted morphology, were observed in the seminiferous tubules. Electron microscopy revealed disordered and missing peripheral microtubule doublets (MTD) and outer dense fibers (ODF) in the sperm flagella, accompanied by a consistent absence of central pairs (CP). The knockout of Ccdc189 resulted in oligo-astheno-teratozoospermia, which is characterized by low sperm count and reduced sperm motility and abnormal morphology. Furthermore, we identified poly(A)-binding protein cytoplasmic 1 (PABPC1) and PABPC2 as interacting proteins with CCDC189. These proteins belong to the poly(A)-binding protein (PABP) family and are involved in regulating mRNA translational activity in spermatogenic cells by specifically binding to poly(A) tails at the 3' ends of mRNAs.

A risk prediction model of gestational diabetes mellitus based on traditional and genetic factors.

BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication during pregnancy. We aimed to evaluate a risk prediction model of GDM based on traditional and genetic factors. METHODS: A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to gather general data. Serum test results were collected from the laboratory information system. Independent risk factors for GDM were identified using univariate and multivariate logistic regression analyses. A GDM risk prediction model was constructed and evaluated with the Hosmer-Lemeshow goodness-of-fit test, goodness-of-fit calibration plot, receiver operating characteristic curve and area under the curve. RESULTS: Among traditional factors, age ≥30 years, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms (SNPs) (rs2779116, rs5215, rs11605924, rs7072268, rs7172432, rs10811661, rs2191349, rs10830963, rs174550, rs13266634 and rs11071657) were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. CONCLUSIONS: Both genetic and traditional factors contribute to the risk of GDM in women, operating through diverse mechanisms. Strengthening the risk prediction of SNPs for postpartum DM among women with GDM history is crucial for maternal and child health protection.

We aimed to evaluate a risk prediction model of gestational diabetes mellitus (GDM) based on traditional and genetic factors. A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to collect general data. Among traditional factors, age ≥30 years old, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. Both genetic and traditional factors increase the risk of GDM in women.

[Construction of a Predictive Model for Diabetes Mellitus Type 2 in Middle-Aged and Elderly Populations Based on the Medical Checkup Data of National Basic Public Health Service]. / åŸºäºŽå›½å®¶åŸºæœ¬å ¬å ±å«ç”ŸæœåŠ¡ä½“æ£€çš„ä¸­è€å¹´äºº2åž‹ç³–å°¿ç— é£Žé™©é¢„æµ‹æ¨¡åž‹æž„å»º.

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.

Effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery: A systematic review and trial sequential analysis of randomized controlled trials.

BACKGROUND: We aimed to verify the effectiveness of electroacupuncture on postoperative ileus prevention after abdominal surgery by meta-analysis and trial sequential analysis (TSA). METHODS: From inception to May 14, 2024, PubMed, the Cochrane Library, Web of Science, and Embase databases were searched. TSA was used to determine an optimal sample size and control false-positive findings. The primary outcome was the time to first defecation (hours). RESULTS: Fourteen studies were included, with 1105 participants. Meta-analysis and TSA revealed firm evidence for benefits that electroacupuncture shorted the time to first defecation (mean difference [MD] -12.73 h, I2 = 22%, P < 0.01), the time to first flatus (MD -7.03 h, I2 = 25%, P < 0.01), the time to start of sips of water (MD -12.02 h, I2 = 0%, P < 0.01), and the time to start of liquid diet (MD -12.97 h, I2 = 0%, P < 0.01) compared with usual care. While compared with sham electroacupuncture, meta-analysis and TSA also confirmed that electroacupuncture shortened the time to first defecation (MD -10.81 h, I2 = 31%, P = 0.02) and the time to first flatus (MD -10.81 h, I2 = 0%, P < 0.01). However, TSA revealed that firm evidence for benefit or futility was not reached for the length of hospital stay and the rates of postoperative prolonged ileus. CONCLUSIONS: Electroacupuncture shortened the duration of postoperative ileus in patients undergoing abdominal surgery, and the adverse events related to electroacupuncture were minor. Further investigation of the effect of electroacupuncture on the risk of prolonged postoperative ileus is warranted in the future.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with basal insulin: a study based on CGM in type 2 diabetes in China.

Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

A Beginner's Guide to Artificial Intelligence for Ophthalmologists.

The integration of artificial intelligence (AI) in ophthalmology has promoted the development of the discipline, offering opportunities for enhancing diagnostic accuracy, patient care, and treatment outcomes. This paper aims to provide a foundational understanding of AI applications in ophthalmology, with a focus on interpreting studies related to AI-driven diagnostics. The core of our discussion is to explore various AI methods, including deep learning (DL) frameworks for detecting and quantifying ophthalmic features in imaging data, as well as using transfer learning for effective model training in limited datasets. The paper highlights the importance of high-quality, diverse datasets for training AI models and the need for transparent reporting of methodologies to ensure reproducibility and reliability in AI studies. Furthermore, we address the clinical implications of AI diagnostics, emphasizing the balance between minimizing false negatives to avoid missed diagnoses and reducing false positives to prevent unnecessary interventions. The paper also discusses the ethical considerations and potential biases in AI models, underscoring the importance of continuous monitoring and improvement of AI systems in clinical settings. In conclusion, this paper serves as a primer for ophthalmologists seeking to understand the basics of AI in their field, guiding them through the critical aspects of interpreting AI studies and the practical considerations for integrating AI into clinical practice.

Associations of anxiety and depression with restless leg syndrome: a systematic review and meta-analysis.

Background: The levels of anxiety and depression among patients with restless leg syndrome (RLS) are controversial. The aim of this systematic review and meta-analysis was to compare the levels of depression and anxiety among individuals with RLS with those of healthy controls. Methods: We conducted an extensive electronic search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from their inception dates to 20 June 2023. Studies presenting data on depression and anxiety in individuals with RLS were included, and a comprehensive meta-analysis was performed. Results: Twenty-one studies matched the inclusion criteria. Significantly more depressive symptoms were present in the individuals with RLS than in those without RLS, as measured by the Beck Depression Inventory [mean difference (MD) = 6.58, 95% confidence interval (CI) = 5.54-7.62, p < 0.01; heterogeneity I2 = 0%, p = 0.99]. Similarly, the results from the Beck Anxiety Inventory indicated that there were significantly more pronounced anxiety symptoms in the individuals with RLS than in those without RLS (MD = 9.30, 95%CI = 7.65-10.94, p < 0.01; heterogeneity I2 = 0%, p = 0.92). The other anxiety and depression scales also yielded statistically significant results. Significant heterogeneity was observed in the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, with the primary contributing factor probably being the scoring criteria of the scales. Conclusion: This meta-analysis found that the levels of depression and anxiety symptoms were significantly higher in individuals with RLS than in their healthy counterparts.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023410364, (identifier CRD42023410364).

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis.

BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Case report: Methicillin-resistant Staphylococcus aureus with penicillin susceptible (PS-MRSA): first clinical report from a psychiatric hospital in China.

This case report documents the first instance of Penicillin-Susceptible Methicillin-Resistant Staphylococcus aureus (PS-MRSA) in a Chinese psychiatric hospital. The strain was isolated from a patient with Alzheimer's disease who had a lower respiratory tract infection. Clinical and laboratory analyses, including mass spectrometry, antibiotic susceptibility testing, and whole-genome sequencing, confirmed the PS-MRSA strain. In this case, we systematically introduce the clinical symptoms, laboratory findings, and treatment responses associated with this PS-MRSA strain. This discovery offers a new perspective on our understanding of resistance mechanisms and expands our considerations for existing antibiotic treatments. It may fill a gap in the classification of MRSA strains, enhance the spectrum of MRSA resistance, and complete the therapeutic strategies for MRSA.

Release Pattern of Light Aromatic Hydrocarbons during the Biomass Roasting Process.

Roasting is an important step in the pretreatment of biomass upgrading. Roasting can improve the fuel quality of biomass, reduce the O/C and H/C ratios in the biomass, and provide the biomass with a fuel quality comparable to that of lignite. Therefore, studying the structure and component evolution laws during biomass roasting treatment is important for the rational and efficient utilization of biomass. When the roasting temperature is 200-300 °C, the cellulose and hemicellulose in the biomass undergo a depolymerization reaction, releasing many monocyclic aromatic hydrocarbons with high reactivity. The proportion of monocyclic aromatic hydrocarbons in biomass roasting products can be effectively regulated by controlling the reaction temperature, residence time, catalyst, baking atmosphere, and other factors in the biomass roasting process. This paper focuses on the dissociation law of organic components in the pretreatment process of biomass roasting.

Whole transcriptome scanning and validation of negatively related genes in UC-MSCs.

Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are one of the most extensively researched stem cell types due to their potential for multi-lineage differentiation, secretion of regenerative factors, modulations of immunological activities, and the release of regenerative substances and influence immunological processes. Since UC-MSCs must be cultivated on a large scale for clinical use, selecting the appropriate storing passage, such as the usage-based passage of UC-MSCs, is critical for long-term autologous or allogeneic usage. Long-term cultivation of stem cells, on the other hand, causes them to lose their pluripotent differentiation capacity. As a result, distinguishing between high and low passages of UC-MSCs and identifying the particular variations associated with stem cells and their modes of action is essential for regenerative medicine. Therefore, we investigated the biological features and transcriptional changes of UC-MSCs over passages. Methods: UC-MSCs were isolated from the tissues of the human umbilical cord, and UC-MSCs from five passages (P1, P3, P5, P10 and P15) with three repetitions were compared and identified based on morphology, cell markers, differentiation capacity, and aging-related characteristics. It was previously assumed that the phenotype of cells before the P10 passage was stable, defined as early passage, and that culture could be continued until the 15th passage, defined as late passage. Next, the five passages of UC-MSCs were sequenced using high-throughput complete transcriptome sequencing. Fuzzy C-Means Clustering (FCM) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to find hub genes, and gene silencing was performed to investigate the impact of missing genes on the stemness of UC-MSC cells. Results: UC-MSCs of different passages displayed similar surface markers, including CD73, CD105, CD90, CD34, CD45 and HLA-DR. However, the proliferation time of late-phase UC-MSCs was longer than that of early-phase UC-MSCs, and the expression of the senescence-associated (SA)-ß-gal staining marker was higher. At the same time, pluripotency markers (NANOG, OCT4, SOX2 and KIF4A) were down-regulated, and the multi-differentiation potential was reduced. Meanwhile, KIFC1 and UBE2C were down-regulated in late-phase UC-MSCs, which were involved in the maintenance of stemness. Conclusions: KIFC1 and UBE2C were highly expressed in early-UC-MSCs and showed a downward gradient trend with cell expansion in vitro. They regulated UC-MSC proliferation, colony sphere formation, multiple differentiation, stemness maintenance, and other biological manifestations. Therefore, they are anticipated to be new biomarkers for UC-MSCs quality identification in regenerative medicine applications.

Secure multi-path routing for Internet of Things based on trust evaluation.

In the realm of the Internet of Things (IoT), ensuring the security of communication links and evaluating the safety of nodes within these links remains a significant challenge. The continuous threat of anomalous links, harboring malicious switch nodes, poses risks to data transmission between edge nodes and between edge nodes and cloud data centers. To address this critical issue, we propose a novel trust evaluation based secure multi-path routing (TESM) approach for IoT. Leveraging the software-defined networking (SDN) architecture in the data transmission process between edge nodes, TESM incorporates a controller comprising a security verification module, a multi-path routing module, and an anomaly handling module. The security verification module ensures the ongoing security validation of data packets, deriving trust scores for nodes. Subsequently, the multi-path routing module employs multi-objective reinforcement learning to dynamically generate secure multiple paths based on node trust scores. The anomaly handling module is tasked with handling malicious switch nodes and anomalous paths. Our proposed solution is validated through simulation using the Ryu controller and P4 switches in an SDN environment constructed with Mininet. The results affirm that TESM excels in achieving secure data forwarding, malicious node localization, and the secure selection and updating of transmission paths. Notably, TESM introduces a minimal 12.4% additional forwarding delay and a 5.46% throughput loss compared to traditional networks, establishing itself as a lightweight yet robust IoT security defense solution.

Identification of Potential Hub Genes Related to Acute Pancreatitis and Chronic Pancreatitis via Integrated Bioinformatics Analysis and In Vitro Analysis.

Acute pancreatitis (AP) and chronic pancreatitis (CP) are considered to be two separate pancreatic diseases in most studies, but some clinical retrospective analyses in recent years have found some degree of correlation between the two in actual treatment, however, the exact association is not clear. In this study, bioinformatics analysis was utilized to examine microarray sequencing data in mice, with the aim of elucidating the critical signaling pathways and genes involved in the progression from AP to CP. Differential gene expression analyses on murine transcriptomes were conducted using the R programming language and the R/Bioconductor package. Additionally, gene network analysis was performed using the STRING database to predict correlations among genes in the context of pancreatic diseases. Functional enrichment and gene ontology pathways common to both diseases were identified using Metascape. The hub genes were screened in the cytoscape algorithm, and the mRNA levels of the hub genes were verified in mice pancreatic tissues of AP and CP. Then the drugs corresponding to the hub genes were obtained in the drug-gene relationship. A set of hub genes, including Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9, were identified through analysis, demonstrating their pivotal roles in the progression from AP to CP. Notably, these genes were found to be enriched in the Helper T-cell factor (Th17) signaling pathway. Up-regulation of these genes in both AP and CP mouse models was validated through quantitative real-time polymerase chain reaction (qRT-PCR) results. The significance of the Th17 signaling pathway in the transition from AP to CP was underscored by our findings. Specifically, the essential genes driving this progression were identified as Jun, Cd44, Epcam, Spp1, Anxa2, Hsp90aa1, and Cd9. Crucial insights into the molecular mechanisms underlying pancreatitis progression were provided by this research, offering promising avenues for the development of targeted therapeutic interventions.

Percutaneous Endoscopic Unilateral-Approach Bilateral Decompression for Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) involves the narrowing of the spinal canal due to degenerative changes in the vertebral joints, intervertebral discs, and ligaments. LSS encompasses central canal stenosis (CCS), lateral recess stenosis (LRS), and intervertebral foramen stenosis (IFS). The utilization of lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has gained popularity in the treatment of CCS and LRS. This popularity is attributed to the rapid development of endoscopic instruments and the progress of endoscopic philosophy. In this technical report, a detailed introduction to the steps and key points of LE-ULBD is provided. Simultaneously, a retrospective review of 132 consecutive patients who underwent LE-ULBD for central canal and/or lateral recess stenosis was conducted. The outcomes after more than two years of follow-up were assessed using the visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and the modified MacNab criteria to evaluate surgical efficacy. All 132 patients underwent LE-ULBD successfully. Among them, 119 patients were rated as "excellent," while 13 patients were rated as "good" based on the modified MacNab criteria during the last follow-up. Incidental dural tears occurred in four cases, but there were no post-operative epidural hematomas or infections. The experience demonstrates that LE-ULBD is a less invasive, effective, and safe approach. It can be considered as an alternative option for treating patients with lumbar central canal stenosis and/or lateral recess stenosis.

Protein arginine methyltransferase 5 in osteoblasts promotes the healing of extraction sockets.

OBJECTIVES: To explore the effect of protein arginine methyltransferase 5 (PRMT5) on tooth extraction sockets healing, we established an extraction sockets model in osteoblast-conditional Prmt5 knockout mice. The results provided clues for promoting extraction sockets healing in clinical settings. MATERIALS AND METHODS: Maxillary first molars were extracted from 6 to 8-week-old mice to establish an extraction fossa model. Microcomputed tomography (Micro-CT), histology, and immunostaining assays were performed on samples harvested at 3-, 7-, and 14-day post-extraction. Prmt5-silenced cell lines  were employed to explore the regulatory mechanisms underlying the osteigenic differentiation. RESULTS: PRMT5 expression was higher in the early stage of socket healing. Micro-CT analysis showed that the percentage of new bone in the extraction sockets was lower in OC-Cre; Prmt5fl/fl mice than in the control group, consistent with Masson staining. We found that, Prmt5 deficiency delayed the osteogenesis during extraction socket healing, which might be achieved through the decrease of H4R3me2s in the Sp7 promoter region. CONCLUSION: PRMT5 in osteoblasts may promote the differentiation of osteoblasts by regulating the Sp7 promoter H4R3me2s and participate in the healing of tooth extraction sockets.

Advances and future perspectives of intranasal drug delivery: A scientometric review.

Intranasal drug delivery is as a noninvasive and efficient approach extensively utilized for treating the local, central nervous system, and systemic diseases. Despite numerous reviews delving into the application of intranasal drug delivery across biomedical fields, a comprehensive analysis of advancements and future perspectives remains elusive. This review elucidates the research progress of intranasal drug delivery through a scientometric analysis. It scrutinizes several challenges to bolster research in this domain, encompassing a thorough exploration of entry and elimination mechanisms specific to intranasal delivery, the identification of drugs compatible with the nasal cavity, the selection of dosage forms to surmount limited drug-loading capacity and poor solubility, and the identification of diseases amenable to the intranasal delivery strategy. Overall, this review furnishes a perspective aimed at galvanizing future research and development concerning intranasal drug delivery.

Effect of different non-pharmacologic placebo treatments on migraine prevention: a network meta-analysis of randomized controlled trials.

BACKGROUND: Placebo control plays an important role in evaluating the effectiveness of interventions. Specifying differential effects of various placebo controls on migraine prevention would be essential in the explanation of preventive treatment for migraine and the indirect comparison between different prophylactic therapeutics. OBJECTIVES: To access the impact of different non-pharmacologic placebo types on different outcomes in migraine patients. METHODS: We searched PubMed, Cochrane Controlled Register of Trials, Embase, and Web of Science databases from the date of creation to June 19, 2023. Randomized controlled trials of migraine that included sham intervention of acupuncture or cognitive behavioural therapy (CBT) or non-invasive Vagus Nerve Stimulation (nVNS) or repetitive Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation (tDCS) were conducted. The primary outcome was the migraine days, and the secondary outcomes were the number of migraine attacks, headache days, headache frequency, and responder's rate. Placebo effects were assessed using five individual placebos for network meta-analysis, using mean differences to measure the relative effect of pair-wise comparisons between interventions. RESULT: A total of 50 trials with 4880 subjects were included. Twenty-seven trials were evaluated for low risk of bias. The results of indirect comparisons show that sham rTMS and sham tDCS had optimal and similar effects in reducing migraine days; sham acupuncture has the greatest effect on reducing the number of migraine attacks and relieving headache frequency; sham rTMS had a highly significant advantage in reducing headache days compared with the other placebo controls. CONCLUSION: Based on the network meta-analysis results, we found that sham acupuncture had the greatest effect on migraine prophylaxis. The strong placebo effect of sham acupuncture should be considered when assessing the therapeutic effect.

Coiled-coil domain containing 159 is required for spermatid head and tail assembly in mice†.

The centrosome is critical for maintaining the sperm head-tail connection and the formation of flagellar microtubules. In this study, we found that in mouse testes, CCDC159 (coiled-coil domain-containing protein 159) is specifically localized to the head-tail coupling apparatus (HTCA) of spermatids, a structure that ensures sperm head-tail tight conjunction. CCDC159 contains a C-terminal coiled-coil domain that functions as the centrosomal localization signal. Gene knockout (KO) of Ccdc159 in mice resulted in acephalic spermatozoa, abnormal flagella, and male infertility. To explore the mechanism behind CCDC159 regulating spermatogenesis, we identified CCDC159-binding proteins using a yeast two-hybrid screen and speculated that CCDC159 participates in HTCA assembly by regulating protein phosphatase PP1 activity. Further RNA-sequencing analyses of Ccdc159 KO testes revealed numerous genes involved in male gamete generation that were downregulated. Together, our results show that CCDC159 in spermatids is a novel centrosomal protein anchoring the sperm head to the tail. Considering the limitation of KO mouse model in clarifying the biological function of CCDC159 in spermatogenesis, a gene-rescue experiment will be performed in the future.