The rules of acupoint selection and treatment were identified and discovered from the collected ancient acupuncture-moxibustion prescriptions recorded the earliest for epigastric pain. The database of ancient acupuncture-moxibustion prescriptions for epigastric pain was set up using Excel2016 software. After the disease term, etiology, pathogenesis, symptoms and acupoints were normalized, the underlying multi-dimensional correlation among the elements of acupuncture-moxibustion was explored, using the frequency statistics and the association rule of Apriori algorithm. In the ancient time, in treatment with acupuncture-moxibustion therapy for epigastric pain, the acupoints of the high use frequency were sequenced as Zhongwan (CV12), Shangwan (CV13), Zusanli (ST36), Neiguan (PC6), Gongsun (SP4), Pishu (BL20) and Weishu (BL21). The common combinations of acupoints included the pairs of back-shu points, the combination of back-shu points and front-mu points, the combination of front-mu points and yuan-source points and the combination of back-shu points and the lower he-sea points. The highly involved acupoints were those from the conception vessel, pericardium meridian, spleen meridian, stomach meridian and bladder meridian; and they were commonly distributed on the abdomen, the yin parts of the foot and the arm, the yang part of the leg and on the back. Regarding the etiologies such as parasites, food retention, masses, qi stagnation and stomach cold, Zhongwan (CV12) and Shangwan (CV13) were coordinated; and Sanyinjiao (SP6) and Daling (PC7) were highly associated with masses. Besides cold injury, parasites and masses, for the epigastric pain caused by other factors of etiology (qi stagnation, stomach cold and food retention), moxibustion therapy was greatly applicable. For epigastric pain combined with qi reversion in the lower abdominal region, Qichong (ST30), Sanyinjiao (SP6), Tianshu (ST25) and Zusanli (ST36) must be selected. Dadu (SP2) and Taibai (SP3) must be used if the distention in the chest and abdomen accompanied; and Zhongzhu (TE3) be used if back pain involved. Zusanli (ST36) was commonly selected for hiccups. For the other accompanied symptoms, Zhongwan (CV12) was used, which is consistent with the acupoint selection of main symptoms. On the trunk, moxibustion was generally used at Weishu (BL21), Pishu (BL20), Geshu (BL17), Zhongwan (CV12), Juque (CV14) and Qihai (CV6), except Shangwan (CV13). Among the acupoints below the elbows and knees, moxibustion was commonly applicable at Zusanli (ST36), and acupuncture was often used at Gongsun (SP4) and Daling (PC7).
Acupuncture Points ; Humans ; Moxibustion/history* ; History, Ancient ; Acupuncture Therapy/history* ; Data Mining ; Abdominal Pain/history*

OBJECTIVE: To observe the effect of acupuncture at "pelvic floor six needles" for mild to moderate female stress urinary incontinence (SUI). METHODS: A total of 60 patients with mild to moderate female SUI were randomly divided into an observation group and a control group, 30 cases each group. The control group received Kegel exercise. The observation group received acupuncture at "pelvic floor six needles" on the basis of the treatment as the control group, bilateral Zhongliao (BL33), Zhibian (BL54), Huiyang (BL35), Shuidao (ST28), Dahe (KI12) and Guanyuan (CV4) were selected, once every other day, 3 times a week, 4 weeks as a course of treatment, a total of 2 courses were required. Before treatment and after 4, 8 weeks of treatment, urine leakage in 1 hour, International Consultation on Incontinence questionnaire short form (ICI-Q-SF) score, and incontinence quality of life questionnaire (I-QOL) score were observed in the two groups, and the clinical efficacy was evaluated. RESULTS: After 8 weeks of treatment, urine leakage in 1 hour and ICI-Q-SF scores in both groups were decreased compared with those before treatment (P<0.05), and urine leakage in 1 hour and ICI-Q-SF score in the observation group were lower than those in the control group (P<0.05). After 4, 8 weeks of treatment, I-QOL scores were increased compared with those before treatment in both groups (P<0.05), and the I-QOL scores in the observation group were higher than those in the control group (P<0.01, P<0.001). The total effective rate of the observation group was 93.3% (28/30), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "pelvic floor six needles" could improve the clinical symptoms and quality of life in patients with mild to moderate female SUI to a certain degree.
Humans ; Female ; Acupuncture Therapy/instrumentation* ; Urinary Incontinence, Stress/physiopathology* ; Middle Aged ; Adult ; Exercise Therapy ; Acupuncture Points ; Pelvic Floor/physiopathology* ; Aged ; Treatment Outcome ; Quality of Life

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*

OBJECTIVE: To retrieve and collate the earliest recorded texts in ancient acupuncture-moxibustion prescriptions for chest obstruction and heart pain, and explore the acupoint composition principles. METHODS: The Excel 2016 software was used to build a data set of ancient textual records on acupuncture-moxibustion prescriptions for chest obstruction and heart pain. After the terminology related to etiology, pathogenesis, accompanying symptoms, acupoints, and treatment methods unified, the frequency statistical analysis and association rule algorithms were applied to analyze the implicit association patterns among various elements of syndrome differentiation, treatment selection, and acupoint selection in ancient prescriptions from multiple dimensions. RESULTS: The basic acupoints of high frequency in ancient acupuncture-moxibustion treatment for chest obstruction and heart pain were Daling (PC7), Neiguan (PC6), Taixi (KI3), Taichong (LR3), Shangwan (CV13), Yongquan (KI1), and Xinshu (BL15). The prescription was mostly composed of yuan-source points. Besides, the combinations of two of five-shu points, five-shu points with luo-connecting points, and yuan-source points with luo-connecting points were common. The high-frequency points were from the pericardium meridian of hand-jueyin, conception vessel, kidney meridian of foot-shaoyin, liver meridian of foot-jueyin, and bladder meridian of foot-taiyang, generally distributed on the yin part of the arm, abdominal region, the yin part of foot, the back, and the yin part of the leg. Zhigou (TE6), Zusanli (ST36), Baihui (GV20), and Jiuwei (CV15), as well as the specific acupoint combinations, were used for chest obstruction and heart pain due to qi stagnation. Moxibustion was more suitable for chest obstruction and heart pain caused by qi reversion, cold and qi stagnation. Shaohai (HT3) was invariably selected when hand tremor was accompanied; Zhongchong (PC9) combined with Daling (PC7) was selected specially for feverish sensation in the palms. Moxibustion was exclusively applied to Shangwan (CV13), and Taixi (KI3) was often stimulated with moxibustion. At Neiguan (PC6) and Daling (PC7), moxibustion was delivered in combination with acupuncture (high confidence was presented in acupuncture). CONCLUSION In ancient acupuncture-moxibustion treatment for chest obstruction and heart pain, the points of the pericardium meridian of hand-jueyin are predominant, coordinated with those of the liver meridian of foot-jueyin, kidney meridian of foot-shaoyin, conception vessel, and bladder meridian of foot-taiyang. It follows the principles of acupoint selection, "the pericardium acting on behalf of the heart", "regulating qi as the priority", "combination of yuan-source points with luo-connecting points", and "selecting nearby points along the affected meridians".
Humans ; Moxibustion/history* ; Acupuncture Therapy/history* ; Acupuncture Points ; History, Ancient ; Data Mining ; Chest Pain/history* ; Prescriptions/history* ; Meridians

Through collecting the existing clinical evidences on acupuncture and moxibustion for urticaria, the distribution of evidence in this field was mapped. A systematic search of Chinese and English literature was conducted in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library for treatment of urticaria with acupuncture and moxibustion, published up to December 31, 2023 since inception of each database. The research status in this field was summarized using an evidence mapping approach, and methodological quality was assessed. A total of 323 randomized controlled trials (RCTs) and 22 systematic reviews were included. The number of studies on acupuncture and moxibustion for urticaria has been increasing, with a significant rise in recent years. In most RCTs, the study scale was small, and the subjects focused on chronic spontaneous urticaria in adolescents and middle-aged adults, aged 14 to 60 years. Regarding the intervention measures, the single therapy of acupuncture and moxibustion was predominant such as acupoint injection, acupoint embedding thread, and filiform needling. In acupuncture with filiform needles, the commonly used acupoints were Quchi (LI11), Xuehai (SP10), Sanyinjiao (SP6), Zusanli (ST36) and Hegu (LI4). The main outcome measures referred to effectiveness rate, score of disease severity, recurrence rate, laboratory indexes, and score of quality of life; and the short-term effect was evaluated specifically. The overall methodological quality of the included studies was relatively low. It is suggested that the future research should focus on large-scale, multi-center, high-quality clinical trials, optimize the protocols for acupuncture and moxibustion intervention, standardize the outcomes, and draw the attention to the evaluation of long-term efficacy, so as to provide clinical evidences of high certainty for urticaria treated with acupuncture and moxibustion.
Humans ; Moxibustion ; Acupuncture Therapy ; Urticaria/therapy* ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Adolescent ; Adult ; Young Adult

In recent years,a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases,including functional gastrointestinal disorders,cardiovascular diseases,as well as anxiety and depression,through the modulation of the paraventricular hypothalamic nucleus(PVN).Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN,such as corticotropin releasing hormone(CRH)neurons,or by regulating the release of hormones,such as oxytocin(OXT)and vasopressin(VP),and the activity of neural circuits associated with the PVN.This review summarizes the mechanisms by which PVN is involved in acupuncture treatment,including its regulatory mechanisms in gastrointestinal diseases,cardiovascular diseases,and negative emotions and pain.Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases,focusing on clarifying the specific processes of signaling pathway transduction,and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.

Objective To investigate the role of long non-coding RNA-small nucleolar RNA host gene 3(lncRNA-Snhg3)and its regulatory mechanism in the hepatic glucose metabolism of mice.Methods Adenovirus Snhg3 was over-expressed by the tail vein injection in db/db mice,and then glucose tolerance and pyruvate tolerance were meas-ured.The mRNA expression of mouse liver gluconeogenesis-related genes phosphoenolpyruvate carboxylase(Pepck)and glucose-6-phosphatase(G6pc)and stress-inducing protein 2(Sestrin2,Sesn2,a gene adjacent to Snhg3)were de-tected by RT-qPCR.The dual luciferase reporter assay was used to detect the effect of Snhg3 on the Sesn2 promoter activity in 293T cells.Results Snhg3 over-expression improved glucose tolerance and pyruvate tolerance in db/db mice.Snhg3 over-expression inhibited the mRNA of gluconeogenesis genes of Pepck(P＜0.05)and G6pc(P＜0.05),while promoted the mRNA of Sesn2(P＜0.01).Meanwhile,Snhg3 over-expression promoted Sesn2 promoter activity in 293T cells(P＜0.05).Conclusions Snhg3 improves glucose metabolism in mice by promoting Sestrin2 expression.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To investigate the effect of microRNA(miR)-4645-5p on the proliferation,invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting mucin 16(MUC16)and its mo-lecular mechanism.Methods The expression of miR-4645-5p in esophageal cancer tissues was analyzed online by TCGA database.The expression level of miR-4645-5p in esophageal cancer cell lines was analyzed by fluo-rescent real-time fluorescence quantitative polymerase chain reaction(qPCR).KYSE-30 cells were transfected with miR-4645-5p mimic and negative control mimic by lipofection technology,and were divided into miR-4645-5p group and control mimic group.The proliferation ability,migration ability and invasion ability of transfected KYSE-30 cells were analyzed by CCK-8 method,scratch test and Transwell test respectively.The target gene of miR-4645-5p was predicted by the bioinformatics website,and the binding of miR-4645-5p to the target gene was detected by the dual-luciferase reporter gene assay.The expression level of MUC16 mR-NA was detected by qPCR,and the protein expression levels of MUC16,transcription factor-1(ZEB-1),zonal atresia protein(ZO-1),tight junction protein-1(Claudin-1)and α-smooth muscle actin(α-SMA)were detected by Western blotting.Results The expression level of miR-4645-5p in esophageal cancer tissues was signifi-cantly lower than that in adjacent tissues(P＜0.01).Compared with HET-1 A,the expression of miR-4645-5p was lower in esophageal cancer cell lines(P＜0.05).After overexpression of miR-4645-5p,the proliferation a-bility of KYSE-30 cells was significantly reduced(P＜0.05),the migration ability was significantly reduced(P＜0.01)and the invasion ability was significantly reduced(P＜0.01).miR-4645-5p targeted and negatively regulated the expression of MUC16 mRNA(P＜0.01).After overexpression of miR-4645-5p,the protein ex-pression levels of MUC16,ZEB-1 and α-SMA were all down-regulated,and the protein expression levels of ZO-1 and Claudin-1 were up-regulated.Conclusion miR-4645-5p regulates the malignant biological behavior of esophageal cancer KYSE-30 cells by targeting MUC16.

Objective To investigate the effect of Nutlin-3a,a mouse double minute 2 homolog(MDM2)inhibitor,on lipid metabolism of mouse adipose.Methods High-fat diet-induced obesity(DIO)C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a.Then we conducted glucose tolerance(GTT)and insulin tolerance(ITT)tests.The epididymal white adipose tissue(eWAT),inguinal white adipose tissue(iWAT)and brown adipose tissue(BAT)of animals were isolated and microscopy of WATs with hematoxylin-eosin(HE)staining was performed to observe the morphological changes of adipocytes.The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C(CIDEC)in eWAT were detected by qPCR and Western blot.Results Compared with the control group,Nutlin-3a was found to promote the body weight(P＜0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice.Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT.Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.