Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

This article summarized the clinical experience of MEI Guoqiang in treating lung cancer of phlegm-heat obstructed in the lung syndrome with modified Xiaoxianxiong Decoction （小陷胸汤）. It is believed that the key pathogenesis of lung cancer with phlegm-heat obstructed in the lung syndrome is the phlegm-heat toxin accumulation. According to the different pathogenic effects of qi stagnation， blood stasis， pathogenic toxin， phlegm-damp， qi deficiency， yin deficiency in the occurrence and development of the disease， it is advocated to clear heat and resolve phlegm， and additionally the methods of diffusing the lung and relieving cough， resolving toxins and dissipating masses， rectifying qi and activating blood， dispelling dampness， supplementing and boosting qi and yin are used if necessary. Multiple methods are used together and flexibly matched. In clinical practice， Xiaoxian-xiong Decoction with the function of clearing heat and relieving phlegm is recommended as the basic formula for further modification. For patients with mild lung symptoms， modified Xiaoxianxiong Decoction is commonly used， while for those with obvious symptoms， self-made Maxing Xianxiong Decoction（麻杏陷胸汤） in modifications is suggested. For patients with Shaoyang （少阳） diseases， modified Chaihu Xianxiong Decoction （柴胡陷胸汤） is often used.

Objective To evaluate the safety and efficacy of 450 nm blue laser vaporization prostatectomy in the treatment of benign prostatic hyperplasia(BPH).Methods A retrospective analysis was conducted on 40 BPH patients treated with 450 nm blue laser vaporization prostatectomy at our hospital during Mar.and Nov.2023.The preoperative and postoperative maximum urinary flow rate(Qmax),post-void residual volume(PVR),international prostate symptom score(IPSS),and quality of life(QoL)score were compared.The operation time,postoperative bladder irrigation time,and postoperative hemoglobin decrease were recorded.Results All operations were successful.One month after surgery,the Qmax[(7.9±2.1)mL/s vs.(16.8±2.5)mL/s]was significantly higher,while PVR[(110.0±42.1)mL vs.(14.6±11.4)mL],IPSS[(25.0±3.1)vs.(11.8±4.0)],and QoL[(5.1±0.9)vs.(2.5±0.6)]were significantly lower,with statistical significance(P＜0.05).The operation time was(52.5±15.5)min,the bladder irrigation time was(22.3±4.9)h,the postoperative hemoglobin drop was(6.5±3.8)g/L.Urinary retention occurred in 2 patients after removal of the catheter.Gross hematuria occurred in 1 patient after discharge.Conclusion Vaporization prostatectomy with 450 nm blue laser can significantly improve clinical symptoms and perioperative safety,with high vaporization efficiency and good hemostatic effects.It is worthy of clinical promotion and application.

Objective To observe the neuropsychiatric behavioral performance of kainic acid(KA)-induced epilepsy rats;investigate gender differences in acute seizure and behavioral performance tasks relating to sense,motor,learning,and memory in the remission phase;and explore the potential neurobiological mechanisms of action.Methods Healthy SD rats aged 4 weeks were randomly divided into control and model groups,with 22 rats in each group(11 males and 11 females).An epileptic rat model was induced by intraperitoneal injection of KA.Seizure latency and frequency within 2 hours of KA injection were observed,seizure grade was assessed using the Racine grade standard,and a cortical electroencephalogram(EEG)was recorded.Behavioral performance was observed in a series of tasks including open field testing,balance beam walking,elevated plus maze,Y-maze,and novel object recognition.The level of GABA in the hippocampus was detected by ELISA,injury to hippocampal neurons was observed by Nissl staining,and the protein expression of synapsin-1 and synaptotagmin 1 in the hippocampus were detected by Western Blot.Results Both male and female rats presented typical epileptic behaviors after KA injection.However,compared with the effects in males,the latency of the first seizure(P=0.014)and Ⅳ～Ⅴ grading in female model rats were more pronounced(P＜0.01),and the frequency of epileptic seizures within 2 hours was significantly reduced(P=0.019).In the open field testing,KA-induced epileptic rats presented more motor but fewer hedonic behaviors,as indicated by the decrease in total movement distance in the central area,compared with the control group.Moreover,grooming frequency was significantly reduced in the female model rats compared with not only that in the control but also that in male model rats(P＜0.01).The model rats spent more time completing and had a higher score in the balance beam walking task,indicating their poorer stability and balance.In the elevated plus maze,the exploration times of male model rats in the closed arm was increased.The preference index of rats for the novel arm or object decreased in the Y-maze and novel object recognition,suggesting impairments to their learning and memory abilities.Moreover,neuronal injuries were found in the hippocampus of the model rats that were accompanied with a decline in GABA concentration and protein expression of synapsin-1 and synaptotagmin 1,with no gender differences.Conclusions Intraperitoneal injection of KA successfully induced an epilepsy rat model.However,there was a gender difference in the characters of acute seizures and performance of sensory,motor,and learning memory during epileptic remission.There was no gender differences in the hippocampal GABA concentration or expression of synaptic plasticity-related proteins,and thus no evidence was found for the mechanisms underlying the gender differences.

Objective:To study the clinically curative effect of ureteroscopic holmium laser lithotripsy combined with intercepted basket of capture and extraction device for stone(N-trap)in treating middle and upper ureteral stones.Methods:A total of 112 patients with middle and upper ureteral stone who were diagnosed and treated in the Department of Urology of the Second Affiliated Hospital of Wannan Medical College from September 2020 to September 2022 were prospectively selected as the study subjects,and they were divided into two groups according to the random number table method,with 56 cases in each group.The control group was treated with ureteroscopic holmium laser lithotripsy alone,and the observation group was treated with ureteroscopic holmium laser lithotripsy combined with N-trap intercepted basket for treatment.The related indicators of surgery,the stone removal effect,renal function indicators,postoperative renal mass,postoperative recurrence and postoperative complications between two groups were compared.The scores of the Wisconsin Stone Quality of Life(WISQOL)questionnaire were used to compare and evaluate the postoperative quality of life between the two groups.Results:There were no significant differences in intraoperative operation time and intraoperative blood loss between the two groups(P>0.05),and the postoperative hospitalization time in the observation group was significantly shorter than that in the control group(t=3.464,P<0.05).The success rate of one-time lithotripsy and the clearance rate of stone within 30 d in the observation group were significantly higher than those in the control group,and the upward movement rate of stones of the observation group was significantly lower than that in the control group,and the difference was statistically significant(x2=6.698,7.240,5.489,P<0.05),respectively.The postoperative serum creatinine(Scr),blood urea nitrogen(BUN)and urine microalbumin(UMA)in the observation group were significantly lower than those in the control group,and the differences were statistically significant(t=6.320,8.115,9.231,P<0.05),respectively.The degree of hydronephrosis at 3,6 and 12 months after surgery in the observation group were significantly lower than those in the control group,and the differences were statistically significant(t=3.218,3.345,2.985,P<0.05),respectively.The recurrence rates at 6 and 12 months after surgery in the inspection group were significantly lower than those in the control group,and the differences were statistically significant(x2=5.114,5.783,P<0.05),respectively.The incidence of postoperative complication in the observation group was significantly lower than that in the control group(x2=4.865,P<0.05).The total score of the each dimension of WISQOL scale,and the total score of energy,sleep status,physical symptoms and overall emotion in the observation group were significantly higher than those in the control group,and the differences were statistically significant(t=3.734,3.889,3.903,4.340,4.650,P<0.05),respectively.Conclusion:The curative effect of ureteroscopic holmium laser lithotripsy combined with N-trap intercepted basket is certain,which can effectively improve the clearance rate of stone,and shorten the postoperative hospitalization time,and reduce the incidence of postoperative complications and recurrence rate,and promote the recovery of renal function,and improve the quality of life of patients after surgery.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.
Mice ; Animals ; Micrognathism ; Masseter Muscle ; Mandible ; Osteogenesis

Objective:To survey the status quo of community practice bases for general practice residency training in Wuhan city.Methods:A questionnaire survey was conducted in 12 community general practice training bases affiliated to 11 tertiary hospitals in Wuhan city from March to June 2021. A total of 123 general practice residents and 41 instructors participated in the survey using the different questionnaires. The contents of questionnaires included the basic conditions of the training base and the current status of training at community base, as well as their satisfaction on the program and related problems. The statistical analysis was performed with SPSS software.Results:The conditions of the 12 primary practice bases met the requirements of the Standard for Standardized Training Bases for General Practice Residents (2019 Revision) in terms of size of community hospitals, qualification of the person in charge and faculty team. The survey showed that only 3 bases had psychiatric department; 7 bases had literature retrieval system; all 12 bases had a teaching secretary, but only 1 had a full-time teaching secretary; all 12 bases had established formal assistant relationship with higher-level hospitals, but the frequency of communication was low in some bases. Survey also showed that 68.3% (28/41) instructors were aged 40-50 years; 90.2% (37/41) of instructors participated in epidemic prevention and control; 36.6% (15/41) thought that instructing work was related to professional promotion; 87.8% (36/41) of instructors were generally satisfied with the work performance. Most of trainees (92.7%, 114/123) were satisfied with the training at the primary base, and there was a difference in satisfaction degree between trainees with different enrollment sources (χ 2=6.92, P=0.032). The proportion of trainees with confidence for future career increased from 39.8% (49/123) before training in community bases to 60.2% (74/123) after training. Conclusions:The survey shows that primary practice bases for general practice residency training in Wuhan have met the basic requirements; however, the evaluation and motivation of teachers need to be improved, the opportunities for trainees to practice in general outpatient clinics should be increased, research and teaching need to be emphasized, and the management of trainees needs to be strengthened.