ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Abstract: To explore the molecular mechanism by which long non-coding RNA Surfactant Associated 1 Pseudogene(SFTA1P) promotes the proliferation and migration of clear cell renal cell carcinoma(ccRCC) cells by regulating the microRNA-182-5p(miR-182-5p)/fibronectin 1(FN1) pathway. Methods: GEPIA2 software was utilized to analyze the expression ofSFTA1Pin ccRCC tissues from the TCGA database. Quantitative real-time PCR(qPCR) was employed to detect the expression ofSFTA1Pin ccRCC tissues, normal kidney tissues and ccRCC cell lines. A subcellular localization experiment was performed to explore the localization ofSFTA1Pwithin the human renal cell adenocarcinoma cell line(ACHN) derived from ccRCC. ACHN cells were then divided into the following groups: si-Con group, si-SFTA1P #2 group, mimic NC group, miR-182-5p mimic group, anti-miR-Con group, anti-miR-182-5p group, anti-miR-182-5p+si-FN1 group, si-Con+anti-miR-Con group, si-SFTA1P #2+anti-miR-Con group, and si-SFTA1P #2+anti-miR-182-5p group. CCK-8 and Transwell chamber experiments were conducted to assess cell proliferation and migration abilities. qPCR, Western blot, and dual-luciferase reporter assays were employed to elucidate the regulatory interactions amongSFTA1P,miR-182-5p, andFN1. Results: Analysis of The Cancer Genome Atlas(TCGA) database indicated thatSFTA1Pwas overexpressed in ccRCC tissues(P<0.05). When compared to normal kidney tissues,SFTA1Pexpression was markedly elevated in ccRCC tissues(P<0.01). Furthermore, the expression levels ofSFTA1Pin ccRCC cell lines 786-O, SN12-PM6, ACHN, and A498 were significantly higher than those in human renal proximal tubule cells(HK-2)(allP<0.01). Subcellular localization experiments revealed thatSFTA1Ppredominantly localized in the cytoplasm of ACHN cells. Compared to the si-Con group, the si-SFTA1P #2 group exhibited a significant reduction in proliferation and migration abilities of ACHN cells, accompanied by a decrease inFN1mRNA and protein expression(P<0.05). Compared to the mimic NC group, the expression ofFN1mRNA and protein in ACHN cells in the miR-182-5p mimic group reduced(P<0.01). In comparison to the anti-miR-Con group, the expression levels ofFN1mRNA and protein in ACHN cells were significantly elevated in the anti-miR-182-5p group. Additionally, there was a significant enhancement in both cell proliferation and migration capabilities(P<0.05). Conversely, the proliferation and migration abilities of ACHN cells in the anti-miR-182-5p+si-FN1 group were significantly reduced compared to the anti-miR-182-5p group(P<0.05). Furthermore, relative to the si-SFTA1P #2+anti-miR-Con group, the ACHN cells in the si-SFTA1P #2+anti-miR-182-5p group demonstrated increased proliferation and migration abilities, along with elevatedFN1mRNA and protein expression levels(P<0.05). Conclusion SFTA1Pexhibits elevated expression levels in ccRCC and facilitates the proliferation and migration of ccRCC cells through the modulation of themiR-182-5p/FN1signaling pathway.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Patients with advanced pregnancy complicated by acute ST-segment elevation myocardial infarction are relatively rare both domestically and internationally,and there are currently no relevant guidelines to guide clinical treatment.In this case,a 39-year-old pregnant woman was admitted to the hospital with sudden chest pain,and the electrocardiogram showed extensive anterior ST-segment elevation myocardial infarction.Coronary angiography showed subtotal subtotal occlusion of the proximal left anterior descending artery.Reperfusion and revascularization were given,and the blood flow grade of the trial of thrombolytic in myocardial infarction was restored.Complete intravascular ultrasonography to determine the cause of occlusion due to spontaneous hematoma of the left anterior descending artery.After the operation,a reasonable antiplatelet and anticoagulant treatment regimen was selected according to the coronary artery lesion,and the pregnancy was terminated at the appropriate time,and 1 live male baby was successfully delivered.Maternal and fetal health was followed up after 1、3 and 6 months.Through the experience and summary of the treatment process,combined with the literature,the pathogenesis of this disease is discussed,and the strategy of revascularization,the selection of antithrombotic drugs and the timing of pregnancy termination are discussed in depth for clinical reference.

AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Objective:To investigate the clinicopathological features, gene mutations, and distribution of bronchial adenoma (BA).Methods:Eighty-eight cases of BA diagnosed via routine section diagnosis between May 2015 and February 2024 were collected at the Pathology Departments of Zhongshan Hospital Affiliated to Fudan University (71 cases), Shanghai, China and Jining No.1 People′s Hospital (17 cases), Jining, China. Clinical data, image features, histopathological sections, immunohistochemical stains, and genetic testing results were reviewed.Results:Among the 88 patients with BA, there were 36 males and 52 females. The incidence of proximal-type BA was the same in both genders (50%, 28/56), while distal-type BA was more commonly found in females (75%, 24/32, P=0.022). BA predominantly affected middle-aged and elderly adults, with an age range of 30-78 years (median, 61 years). Clinically, BA generally presented without obvious symptoms. Radiologically it mainly manifested as peripheral lung ground-glass nodules, mixed ground-glass nodules, or solid nodules, primarily located in the lower lobes of the lungs (72.7%, 64/88). Proximal-type BA was characterized by solid nodules (53.6%, 30/56), while distal-type BA by ground-glass nodules (56.3%, 18/32), with a statistically significant difference between the two types ( P<0.01). The tumor was non-encapsulated, with a gray-white cut surface, and some areas were gray-brown. In 18.2% (16/88) of cases, the cut surface was slippery, with soft to medium-firm consistency and poorly defined margins. The smooth texture was predominantly found in proximal-type BA (14/16), whose tumor diameters ranged from 0.2 to 4.6 cm. Microscopically, the lesions exhibited glandular, papillary, or relatively flat patterns, with the main cellular components consisting of basal cells, ciliated columnar cells, mucinous cells, and alveolar epithelial cells in various proportions. Proximal-type BA resembled the morphology of proximal bronchioles and commonly contained mucinous and ciliated cells, while distal-type BA typically lacked mucinous and ciliated cells. The frequency of ciliated cell micropapillae in proximal-type BA (64.3%, 36/56) was significantly higher than that in distal-type BA (31.3%, 10/32, P=0.003). The morphological manifestation of glandular duct dilation was more commonly noted in proximal-type BA (98.2%, 55/56) than that in distal-type BA (81.25%, 26/32, P=0.009). Overall, the disagreement rate between frozen-section and routine diagnoses was 19.5% (17/87). Immunohistochemistry for cytokeratin 5/6 (CK5/6) and p40 showed that basal cell continuity in proximal-type BA (82.1%, 46/56) was significantly higher than that in distal-type BA (56.2%, 18/32, P=0.009). Molecular testing showed an accumulative gene mutation rate of 60.5% (23/38) in BA, including mutations in BRAF V600E (34.2%, 13/38), KRAS (18.4%, 7/38), ALK (5.3%, 2/38), and EGFR (2.6%, 1/38). Proximal-type BA was associated with BRAF V600E mutations, while distal-type BA with KRAS mutations ( P=0.025). Conclusions:BA is a rare benign bronchial tumor and has a high diagnostic error-rate on intraoperative frozen section. Proximal-type BA often presents with ciliated cell micropapillae, which supports the diagnosis, while distal-type BA frequently shows a partial reduction or absence of basal cells, increasing the diagnostic difficulty. The different subtypes of BA exhibit distinct genetic (mutation) profiles that may assist in its diagnosis and histological classification

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.