Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

Objective: To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging. Methods: Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated. Results: Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05). Conclusion With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

BACKGROUND:It was found that the ligands and receptors of Notch are both cell membrane surface proteins,which are important proteins to mediate intercellular communication,and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells,summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,and provide theoretical support for the future use of stem cells to treat various related diseases. METHODS:By using the computer,the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI,Wanfang,VIP,PubMed,Web of Science,and Nature databases with Chinese search terms"mesenchymal stem cells,Notch,Notch signaling pathway,proliferation,differentiation"and the English search terms"mesenchymal stem cells,MSC,Notch,Notch signaling pathway,proliferation,differentiation".Part of the literature was searched in combination with the literature tracing method.Finally,87 articles were included in the review analysis. RESULTS AND CONCLUSION:(1)Notch signaling pathway is a conserved signaling pathway in multicellular organisms,which plays an important role in regulating cell differentiation,proliferation,apoptosis,and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding.(2)Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential,which can be regulated by external signaling pathways to affect their proliferation and differentiation.Notch signaling pathway,as one of them,when Notch ligands are activated,the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD,which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources,such as bone marrow,adipose,and umbilical cord.However,the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different.(3)The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells,but due to different target cells,the expression levels of receptors or ligands in the Notch signaling pathway vary.(4)Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases,such as aplastic anemia,severe joint injuries,ischemic strokes,and myocardial infarctions,has a promising application.(5)By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat,mouse,and human,it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different.(6)The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety,low immune rejection,and wide therapeutic prospects.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors,and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

Objective To investigate air radioactivity contamination, surface contamination, ambient dose equivalent rates, and radiation doses to individuals in the treatment room during ¹⁷⁷Lu-DOTATATE therapy. Methods A ward for ¹⁷⁷Lu-DOTATATE therapy was selected in the nuclear medicine department of a general hospital. Air and surface radioactivity samples were collected before and after therapy for four patients. Ambient dose equivalent rates were measured around the four patients following the initiation of ¹⁷⁷Lu-DOTATATE therapy. Measurements were taken at distances of 0.1, 0.3, 0.5, and 1−4 m (with 0.5 m intervals) from the right lateral midsection of the patient’s torso. The measurement time points included 5, 15, and 30 min after initiation of administration, as well as 0−4 h (with 1 h intervals), 24 h, and 48 h post-administration. Radiation exposure doses for personnel at different distances from the patients were calculated for each time interval. Results The results of radioactive aerosol detection for all four patients during and after the administration of ¹⁷⁷Lu-DOTATATE were similar to those before administration. Surface contamination was not detected at the measurement locations except for patient number 2. The ambient dose equivalent rates increased with increasing injection dose during the administration. However, the ambient dose equivalent rates decreased significantly within one hour after administration. At the end of the administration, the average ambient dose equivalent rate at a distance of one meter for the four patients was 42.931 μSv/h. From the start of administration to four hours post-administration, personnel maintaining a distance of one meter from the patient received a total radiation dose of 167.64 μSv. Conclusion Air radioactivity contamination does not occur during ¹⁷⁷Lu-DOTATATE therapy. However, measures should be taken before the commencement of therapy to address potential surface contamination. Both accompanying persons and healthcare staff receive radiation doses below the stipulated dose constraints throughout the treatment process. Therefore, it is necessary to implement appropriate measures to minimize the radiation exposure of healthcare staff.

Objective:To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation.Methods:Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization.Results:ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions:This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

Objective To analyze the distribution characteristics and application value of liver,renal func-tion indexes and autoantibody-related indexes of neuromyelitis optica spectrum disorder(NMOSD).Methods The liver,renal function and autoantibody-related indexes data of patients diagnosed with NMOSD and multiple sclerosis(MS)in Beijing Tiantan Hospita,Capital Medical University from June 2015 to June 2023,as well as gender and age-matched controls underwent routine physical examination were retrospectively collected.A total of 95 patients with NMOSD(NMOSD group),230 patients with MS(MS group),and 244 healthy controls(routine physical examination group)were selected to evaluate the diagnostic value of each index for NMOSD.Results Compared with MS group,the levels of alanine aminotransferase,as well as the positive rates of α-hydroxybutyrate dehydrogenase,y-glutamyltransferase,anti-SS-A antibody,anti-SS-B anti-body,anti-ribosomal P protein antibody and Ro-52 antibody were significantly increased in NMOSD group,while the levels of albumin,indirect bilirubin and total bilirubin were significantly decreased,and the differ-ences were statistically significant(P＜0.05).The difference index between NMOSD and conventional physi-cal examination group was similar to that of MS group.The seven indexes,a-hydroxybutyrate dehydrogenase,albumin,globulin,direct bilirubin,indirect bilirubin,total bile acid and uric acid alkalinity could be used for the diagnosis of NMOSD.The area under the curve of combined diagnosis of NMOSD was 0.969,and the sensitiv-ity and specificity were 92.6％and 92.9％.Conclusion Multiple indexes of liver and kidney function in NMOSD patients are different from those in MS patients and healthy subjects underwent routine physical ex-amination,and the positive rate of some autoantibody indexes in NMOSD patients is higher than that in MS patients.Liver,renal function and autoantibody-related indexes can be used clinically to assist diagnosis,and the combined application of multiple indexes can further enhance its diagnostic value.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.