OBJECTIVE: To observe the distribution characteristics of sensitization areas on the body surface in the rat models with functional constipation and diarrhea, explore the regulatory patterns of electroacupuncture (EA) of different intensities at "Tianshu" (ST25) on distal colon motility, and clarify the roles of the neurons of different subtypes in the enteric nervous system (ENS) displayed in the regulatory effect. METHODS: Of 90 SD male rats of SPF grade, 15 rats were randomized into a normal group, a constipation group and a diarrhea group, 5 rats in each one. The stool form and fecal water content, as well as the distribution of the Evans blue (EB) extravasation on the body surface after the intravenous injection with EB on the tails were observed. Eighteen rats were randomized into a normal +2 mA group, a normal +4 mA group and a normal + 6 mA group, 6 rats in each one. Using physiological signal acquisition system, the area under the curve and the average amplitude of colon peristalsis were recorded and analyzed, and the immediate effect on distal colon peristalsis observed after EA with different intensities at "Tianshu" (ST25). Thirty rats were randomized into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea +6 mA group, 6 rats in each one, so as to observe the cumulative effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Twelve rats were randomized into a constipation +2 mA group and a diarrhea +6 mA group, 6 rats in each one, to observe the immediate effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Fifteen rats were randomly divided into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea + 6 mA group, 3 rats in each one. Using the whole-mount staining technique, the expression of vesicular acetylcholine transporter (VAChT)-positive neurons and nitric oxide synthase (nNOS)-positive neurons in ENS was detected. According to the group divisions, the functional constipation models were established by intragastric administration of loperamide hydrochloride (10 mg/kg, once daily, for consecutive 7 days), and the functional diarrhea models were prepared by intragastric administration of folium sennae decoction (10 mL/kg, once daily, for consecutive 2 days). The interventions were delivered with EA of different intensities (the electric current of 2, 4 or 6 mA) at bilateral "Tianshu" (ST25), separately, with the continuous wave and the frequency of 10 Hz used. RESULTS: Compared with the normal group, the fecal amount was decreased, and the fecal water content was reduced in the rats of the constipation group (P<0.001); and loose stool was presented and the fecal water content increased in rats of the diarrhea group (P<0.001). EB extravasation on the body surface happened in the region from T₆ to S₂ of the rats in the constipation and diarrhea groups, and it was more concentrated in the lower abdominal and the lower back regions from T₁₀ to L₃. Compared with the indexes before EA, in the normal +2 mA group and the normal +4 mA group, the areas under the curve and the average amplitude of the distal colon peristalsis were higher during EA delivery (P<0.01, P<0.05), showing a stimulatory immediate effect; and the post-effect was obtained after EA at 2 mA. Whereas, these two indexes were declined during EA in the rats of the normal +6 mA group (P<0.001), showing an inhibitory immediate effect. After many interventions with EA, when compared with those before EA, the above two indexes rose in the constipation +2 mA group (P<0.05, P<0.01), and they were dropped in the diarrhea +6 mA group (P<0.01, P<0.05). The area under the curve of the colon peristalsis in the constipation +2 mA group was higher than that of the constipation group (P<0.001), and that in the diarrhea +6 mA group was lower compared with that in the diarrhea group (P<0.001). The stimulatory effect of EA on colon motility in the constipation +2 mA group was stronger than that of the normal + 2 mA group (P<0.05), and its inhibitory effect was not different statistically in comparison between the normal +6 mA group and the diarrhea +6 mA group (P>0.05). In ENS of the distal colon, after EA at 2 mA, the proportion of VAChT-positive neurons was higher than that of the activated nNOS-positive neurons (P<0.001); and after EA at 6 mA, the activated nNOS-positive neurons were dominant (P<0.001). CONCLUSION In the functional constipation and diarrhea rat models, the sensitization areas on the body surface are centralized in the lower abdominal and the lower back regions of T₁₀ to L₃. Electroacupuncture at "Tianshu" (ST25) has a bidirectional regulatory effect on distal colon motility, and this effect is coordinated with the intensity of electroacupuncture, and may be mediated by ENS neurons of different subtypes.
Animals ; Electroacupuncture ; Male ; Rats ; Colon/innervation* ; Acupuncture Points ; Rats, Sprague-Dawley ; Constipation/physiopathology* ; Gastrointestinal Motility ; Humans ; Diarrhea/physiopathology*

This paper reports a case of head-facial herpes zoster in perimenopausal woman treated with Zheng's cold reducing acupuncture. The patient presented with a syndrome of yin deficiency and internal heat, the treatment principles focused on clearing heat and toxins, nourishing yin and promoting fluid production, achieved through acupuncture. Local surrounding needling was applied around the lesions, supplemented by Zheng's cold reducing acupuncture at head and facial acupoints (including bilateral Fengchi [GB20], Tianzhu [BL10], and Shangxing [GV23], Baihui [GV20], as well as Shuaigu [GB8], Touwei [ST8] on the affected-side) and limb acupoints (including bilateral Lieque [LU7], Neiguan [PC6], Hegu [LI4], Diwuhui [GB42]). Each session lasted 20 min, administered once daily for 8 consecutive days, followed by a 3-day break. An additional session was performed post-break to consolidate efficacy, totally 9 sessions. After treatment, the herpes lesions subsided, and perimenopausal symptoms significantly improved. A 2-month follow-up revealed no residual complications, with the patient in good condition.
Humans ; Female ; Acupuncture Therapy ; Herpes Zoster/therapy* ; Middle Aged ; Perimenopause ; Acupuncture Points ; Head/virology* ; Face/virology*

Objective:To evaluate the clinical efficacy of endoclip papillaplasty (ECPP) for preventing recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on 1 941 patients who underwent ERCP for choledocholithiasis in Henan Provincial People's Hospital from January 2019 to December 2023. A total of 250 patients who received ECPP were assigned to the ECPP group, while 251 matched controls were selected via 1∶1 year-stratified sampling into the control group. After follow-up, 209 ECPP cases and 190 controls were ultimately included in the analysis. Stone removal success rate, incidence of perioperative complications, and postoperative choledocholithiasis recurrence were compared between the two groups. Univariate and multivariate logistic regression were used to determine the risk factors for choledocholithiasis recurrence after ERCP.Results:Both groups achieved 100.0% stone removal success rate. There was no significant difference in the incidence of intraoperative perforation [0.5% (1/209) VS 1.1% (2/190), χ2=0.01, P=0.934], postoperative hyperamylasemia [21.5% (45/209) VS 17.4% (33/190), χ2=1.10, P=0.295] or post-ERCP pancreatitis [3.8% (8/209) VS 8.1% (9/190), χ2=0.20, P=0.653] between the ECPP group and the control group. The ECPP group showed significantly lower bleeding rate [5.1% (11/209) VS 12.3% (23/190), χ2=5.98, P=0.014] and choledocholithiasis recurrence rate [10.5% (22/209) VS 18.9% (36/190), χ2=5.68, P=0.017] compared with the control group. The multivariate logistic regression identified dilated common bile duct diameter ( OR=1.881, 95% CI: 1.101-3.213, P=0.021) as an independent risk factor for choledocholithiasis recurrence, while being female ( OR=0.482, 95% CI: 0.266-0.875, P=0.016) and ECPP ( OR=0.497, 95% CI:0.278-0.887, P=0.018) were protective factors. Conclusion:ECPP effectively reduces choledocholithiasis recurrence rate and bleeding risk after ERCP. ECPP and being female serve as protective factors for choledocholithiasis recurrence, while dilated bile duct diameter is an independent risk factor.

Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.

Objective:To systematically evaluate the current status of research on the development of indicators for entrustable professional activities (EPAs) of residents in China.Methods:We searched the China National Knowledge Infrastructure, Wanfang Data, Airiti Library, PubMed, Embase, and Web of Science databases for literature on the development of EPA indicators for residents in China published between January 1, 2005 and February 28, 2025. Two researchers independently screened the literature and extracted data, followed by descriptive analysis. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tool for expert opinion. Quantitative data were presented as medians (ranges) and qualitative data were presented as frequencies (percentages).Results:A total of eight articles were included, in which two general EPA indicator systems and six specialty-specific EPA indicator systems were developed for residents. The overall quality of the research was high, with the main shortcomings related to the methods used in the process of constructing the consensus indicators. The number of experts recruited ranged from 22 to 45, with 100.00% response rate, high authority coefficients (0.820-0.914), and high coordination coefficients (0.157-0.741). Most of the studies used literature reviews as one source for the indicator pool (8 studies, 100.00%), employed the Delphi method to reach consensus (6 studies, 75.00%), and provided inclusion criteria for the indicators (7 studies, 87.50%). However, only one study (12.50%) explored the practical application of the developed indicators, and none of the studies set indicator weights or conducted quality assessments. The number of EPA indicators developed ranged from 10 to 38 per study. The reporting of EPA indicators was included in most studies regarding titles (8 studies, 100.00%) and the expected levels of entrustment at various stages of training (6 studies, 75.00%), but the reporting on other aspects was lacking. Among the specialty-specific EPA indicators, 38.39% overlapped with the general EPAs indicators.Conclusions:The research on the development of EPA indicators for residents in China is still in its early stages, and there is room for improvement in methodological quality and reporting coverage. There is partial overlap between specialty-specific and general EPA indicators, failing to fully reflect the unique characteristics of different specialties.

Objective:To compare the accuracy of a Chinese large language model (LLM) and radiologists in Chinese middle level professional qualification examination of radiology, and evaluate the quality of answer reasoning provided by the Chinese LLM.Methods:In this study, 100 high-quality questions were selected using stratified random sampling to form a test set. We asked the ERNIE Bot by dialogues on the website to provide the correct answers and answer reasoning for these questions. These questions were also answered by 15 radiologists with different levels of experience. The accuracy of Chinese LLM and that of radiologists were compared. Two radiologists evaluated the quality of answer reasoning using a 5-point semi-quantitative scale.Results:The accuracy of ERNIE Bot was 60.00%, which was lower than the median (interquartile) accuracy of 67.00% (64.00%, 73.00%) for radiologists, and the difference was statistically significant ( W=2.47, P=0.013). The word count of the reasoning provided by Ernie Bot was (196.44±99.25) words, with no significant difference in word count between correct and incorrect answer reasoning, which were (211.03±107.53) words and (174.55±81.84) words, respectively ( t=1.82, P=0.072). Among the correct answers, the quality of reasoning was scored as follows: 1 point for 3 questions, 2 points for 9 questions, 3 points for 12 questions, and 4 points for 36 questions. No reasoning received a score of 5. Conclusions:Chinese LLM demonstrates a certain level of medical knowledge and clinical reasoning ability, which can assist clinical teachers in educational activities. However, it is not yet able to independently tutor residents and lacks the ability of invitational and heuristic teaching.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: To investigate the role and mechanism of the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon gene (cGAS/STING) pathway in oleic acid-induced acute lung injury (ALI) in mice. METHODS: Male wild-type C57BL/6J mice were randomly divided into five groups (each n = 10): normal control group, ALI model group, and 5, 50, 500 μg/kg inhibitor pretreatment groups. The ALI model was established by tail vein injection of oleic acid (7 mL/kg), while the normal control group received no intervention. The inhibitor pretreatment groups were intraperitoneally injected with the corresponding doses of cGAS inhibitor RU.521 respectively 1 hour before modeling. At 24 hours post-modeling, blood was collected, and mice were sacrificed. Lung tissue pathological changes were observed under light microscopy after hematoxylin-eosin (HE) staining, and pathological scores were assessed. Western blotting was used to detect the protein expressions of cGAS, STING, phosphorylated TANK-binding kinase 1 (p-TBK1), phosphorylated interferon regulatory factor 3 (p-IRF3), and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in lung tissue. Immunohistochemistry was performed to observe STING and p-NF-κB positive expressions in lung tissue. Serum interferon-β (IFN-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the normal control group, the ALI model group exhibited significant focal alveolar thickening, intra-alveolar hemorrhage, pulmonary capillary congestion, and neutrophil infiltration in the pulmonary interstitium and alveoli, along with markedly increased pathological scores (10.33±0.58 vs. 1.33±0.58, P < 0.05). Protein expressions of cGAS, STING, p-TBK1, p-IRF3, and p-NF-κB p65 in lung tissue significantly increased [cGAS protein (cGAS/β-actin): 1.24±0.02 vs. 0.56±0.02, STING protein (STING/β-actin): 1.27±0.01 vs. 0.55±0.01, p-TBK1 protin (p-TBK1/β-actin): 1.34±0.03 vs. 0.22±0.01, p-IRF3 protein (p-IRF3/β-actin): 1.23±0.02 vs. 0.36±0.01, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 1.30±0.02 vs. 0.53±0.02, all P < 0.05], positive expressions of STING and p-NF-κB in lung tissue were significantly elevated [STING (A value): 0.51±0.03 vs. 0.30±0.07, p-NF-κB (A value): 0.57±0.05 vs. 0.31±0.03, both P < 0.05], and serum IFN-β levels were also significantly higher (ng/L: 256.02±3.84 vs. 64.15±1.17, P < 0.05). The cGAS inhibitor pretreatment groups showed restored alveolar structural integrity, reduced inflammatory cell infiltration, and decreased hemorrhage area, along with dose-dependent lower pathological scores as well as the protein expressions of cGAS, STING, p-TBK1, p-IRF3 and p-NF-κB p65 in lung tissue, with significant differences between the 500 μg/kg inhibitor group and ALI model group [pathological score: 2.67±0.58 vs. 10.33±0.58, cGAS protein (cGAS/β-actin): 0.56±0.03 vs. 1.24±0.02, STING protein (STING/β-actin): 0.67±0.03 vs. 1.27±0.01, p-TBK1 protein (p-TBK1/β-actin): 0.28±0.01 vs. 1.34±0.03, p-IRF3 protein (p-IRF3/β-actin): 0.32±0.01 vs. 1.23±0.02, p-NF-κB p65 protein (p-NF-κB p65/β-actin): 0.63±0.01 vs. 1.30±0.02, all P < 0.05]. Compared with the ALI model group, positive expressions of STING and p-NF-κB in lung tissue were significantly reduced in the 500 μg/kg inhibitor group [STING (A value): 0.40±0.01 vs. 0.51±0.03, p-NF-κB (A value): 0.43±0.02 vs. 0.57±0.05, both P < 0.05], and serum IFN-β levels were also markedly reduced (ng/L: 150.03±6.19 vs. 256.02±3.84, P < 0.05). CONCLUSIONS The cGAS/STING pathway is activated in oleic acid-induced ALI, leading to exacerbated inflammatory responses and increased lung damage. RU.521 can inhibit cGAS, thereby down-regulating the expression of pathway proteins and cytokines, and providing protection to lung tissue.
Animals ; Acute Lung Injury/chemically induced* ; Male ; Nucleotidyltransferases/metabolism* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Membrane Proteins/metabolism* ; Oleic Acid/adverse effects* ; Transcription Factor RelA/metabolism* ; Lung/pathology* ; Interferon Regulatory Factor-3/metabolism* ; Disease Models, Animal

Objective:To investigate the expression of placenta expressed transcript 1(Plet1)in ovarian tissue of the letrozole-induced model rats of polycystic ovary syndrome(PCOS)and its effect on the proliferation of rat ovarian granulosa cells,and to clarify the possible mechanism by which Plet1 may contribute to the pathogenesis of PCOS.Methods:The ovarian tissue samples from the rats collected in previous studies were used and divided into control and PCOS groups.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of Plet1 mRNA and protein in ovarian tissue of the rat in two groups.Additionally,twenty-four rats underwent vaginal smear cytology were divided into four groups by estrous cycle phase:proestrus,estrus,metestrus and diestrus.RT-qPCR was used to detect the expression level of Plet1 mRNA in ovarian tissue of the rats in various groups,and immunohistochemistry(IHC)method was used to detect the location of Plet1 expression in the rat ovarian tissue in various groups.The rat ovarian granulosa cells were transfected and divided into control group,si-Plet1-rat-266 group,si-Plet1-rat-383 group,and si-Plet1-rat-554 group.Cell counting kit-8(CCK-8)method was used to assess the cell proliferation activities of rat ovarian granulosa cells in various groups,and RT-qPCR method was used to detect the expression levels of cyclin-d epend ent kinase 6(CDK6)and P53 mRNA in rat ovarian granulosa cells in various groups.Results:The RT-qPCR results revealed that Plet1 mRNA was expressed in the ovaries of normal rats,while no statistically significant difference was observed across estrous cycle phases(P＞0.05).The immunohistochemistry results showed that the expression of Plet1 protein was mainly localized in ovarian granulosa cells and luteal cells in the rat ovarian tissue.Compared with control group,the expression levels of Plet1 mRNA and protein in ovarian tissue of the rats in PCOS group were significantly decreased(P＜0.05).The RT-qPCR results showed that compared with control group,the expression level of Plet1 mRNA in ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.01),exhibiting the most pronounced reduction.Compared with control group,the proliferation activity of rat ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.05).Compared with control group,the expression levels of CDK6 and P53 mRNA in rat ovarian granulosa cells in si-Plet1-rat-383 group were significantly decreased(P＜0.05 or P＜0.01).Conclusion:Plet1 protein is predominantly expressed and localized in granulosa cells and luteal cells in normal rat ovarian tissue.Its expression is downregulated in the ovarian tissue of PCOS model rats,and interference with Plet1 gene expression may inhibit the proliferation of rat ovarian granulosa cells.