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Ning Luo,1,* Yi-Chen Zeng,1,* Bai-Tian Fu,1 Je Wie Low,2 Jian-Qiao Fang1 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Institute of International Education of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Qiao Fang, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email fangjianqiao7532@163.comIntroduction: Diabetic peripheral neuropathy (DPN) affects patients’ quality of life significantly. To date, selecting the appropriate treatment remains challenging. While electroacupuncture (EA) has shown promise as an effective adjunct therapy for DPN, and infrared thermography (IRT) has been considered as a potential predictor of treatment efficacy, the evidence for both remains inconclusive. As such, the objectives of this trial are twofold: to ascertain the efficacy of EA for DPN, and to explore the feasibility of IRT as an adjunctive objective tool for efficacy assessment.Methods: The study was designed as a randomized, parallel, controlled trial. It spanned over 6 weeks of treatment and an additional 4 weeks of follow-up. 104 eligible participants will be stratified for severity of disease: mild with Toronto clinical scoring system(TCSS) score 6– 8, moderate (TCSS score 9– 11), and severe (TCSS score 12– 19), and each level will be randomised in a 1:1 ratio into a EA group and waiting-list group. The waiting-list group received only the current conventional medication, while the EA group received an additional 12 EA sessions on top of the conventional medication. The primary outcome indicators is nerve conduction velocity (NCV), which will be tested at the baseline and week 6. Total clinical efficiency, TCSS, Clinical symptoms score of Traditional Chinese Medicine (TCM), Patient global impression of change(PGIC), Temperature of regions of interest (ROIs), and Physico chemical examination will be used as secondary outcome indicators. In addition, safety assessment will be determined based on adverse events during the trial.Conclusion: The expected results of this study will determine whether EA improves efficacy in the treatment of DPN with an acceptable safety profile, and investigating variations in the efficacy of EA across different levels of DPN severity. Furthermore, it will explore the viability of IRT as an objective measure for evaluating treatment effectiveness for DPN.Clinical Trial Registration: ClinicalTrials.gov identifier, NCT06054087.Keywords: electroacupuncture, waiting-list, diabetic peripheral neuropathy, clinical trial, infrared thermography

Yuanyuan Wu,1 Xinmiao Yao,2 Yongliang Jiang,1 Xiaofen He,1 Xiaomei Shao,1 Junying Du,1 Zui Shen,1 Qiaoying He,1 Jianqiao Fang1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, China Abstract: Pain is considered a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. The negative affective-motivational component of pain is different from the sensory component and amplifies the pain experience. Nowadays, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. In the present study, we investigated the pain aversion and anxiety-like behavior of the complete Freund’s adjuvant (CFA)-induced chronic pain model. CFA rats experienced spontaneous pain during pain-paired conditioning (pain aversion) and spontaneous pain produces an affective response (anxiety-like behavior). Moreover, pain aversion was gradually attenuated, while the anxiety-like behavior increased in 4 weeks. Therefore, although the negative effect (including pain aversion and anxiety) is always associated with hyperalgesia, the manifestations of negative effect may follow different time courses, which may influence the progress of primary disease. The findings illustrate that targeted therapy should focus on a specific aspect in different stages of pain. Our study emphasizes the necessity of using multiple tests to study pain comorbidities. Keywords: pain, pain aversion, pain affection, anxiety-like behavior, chronic inflammatory pain, rat

Study Objective: To investigate the efficacy and safety profiles of corticosteroid therapy in severe acute respiratory syndrome (SARS) patients.Design: Four hundred one of 1,278 SARS cases treated in Guangzhou China between December 2002 and June 2003 fulfilled the diagnostic criteria issued by the World Health Organization for confirmed identification of SARS. Among them, the diagnosis of critical SARS was defined by criteria of SARS guidelines incorporated with a low oxygenation index (OI) [< 300 mm Hg]. Data of these patients retrieved from a database were retrospectively analyzed by logistic regression and Cox regression for the effect of corticosteroid therapy on death, hospitalization days, and complication presentation.Results: Among the 401 SARS patients studied, 147 of 249 noncritical patients (59.0%) received corticosteroids (mean daily dose, 105.3 +/- 86.1 mg) [+/- SD], and all survived the disease; 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 +/- 102.3 mg, and 25 died. Analysis of these 401 confirmed cases did not show any benefits of corticosteroid on the death rate and hospitalization days. However, when focused on 152 critical SARS cases, factors correlated with these end points indicated by univariate analysis included use of corticosteroid, age, rigor at onset, secondary respiratory infections, pulmonary rales, grading of OI, and use of invasive ventilation. After adjustment for possible confounders, treatment with corticosteroid was shown contributing to lower overall mortality, instant mortality, and shorter hospitalization stay (p < 0.05). Incidence of complications was significantly associated with the need for invasive ventilation but not with use of corticosteroids.Conclusion: This Guangzhou retrospective study revealed that proper use of corticosteroid in confirmed critical SARS resulted in lowered mortality and shorter hospitalization stay, and was not associated with significant secondary lower respiratory infection and other complications. [ABSTRACT FROM AUTHOR]

Background: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia., Objective: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN., Methods: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach., Results: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I 2 =99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I 2 =0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups., Conclusions: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Postpartum hemorrhage (PPH) is a common cause of maternal death worldwide, but data on PPH incidence and influencing factors for nulliparous and multiparous women is scarce. So, the study aimed to assess the differences in PPH incidence and influencing factors between nulliparous and multiparous women., Methods: A multicenter retrospective cohort study was conducted among women who gave birth at ≥ 28 weeks of gestation in Hunan Province, China, from January 2017 to December 2018. Logistic regression assessed PPH-influencing factors, and the receiver operating characteristic curve (ROC curve) assessed the predictive performance of identified factors., Results: A total of 144,845 postpartum women were included in the study. The incidence of PPH (blood loss ≥ 500 ml) was 2.1 % and 1.7 % for nulliparous and multiparous women, respectively. Among the nulliparous and multiparous women, similar influencing factors of PPH included erythrocyte suspension transfusion before childbirth, anemia, soft-birth canal avulsion, Cesarean-section, placenta abruption, and general anesthesia administration before birth. Thrombophlebitis was associated [aOR 18.46(1.67-20.31)] with PPH among only the nulliparous women, while instrument-assisted birth [aOR 1.95(1.16-3.28)] and gestational hypertension [aOR 1.57(1.13-2.19)] were associated with PPH among only the multiparous women. The areas under the ROC-curve for the overall-cohort, nulliparous, and multiparous groups were [0.829(0.821-0.838)], [0.828(0.815-0.840)] and [0.833(0.822-0.844)], respectively., Conclusion: PPH incidence is higher among nulliparous women than among multiparous women, but influencing factors vary relatively by parity. The study findings provide new insights into the use of different approaches to PPH prevention for nulliparous and multiparous women in clinical practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1β and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: This study aims to explore the efficiency and effectiveness of a body area network-based smart bracelet for trauma care prior to hospitalization., Methods: To test the efficacy of the bracelet, an observational cohort study was conducted on the clinical data of 140 trauma patients pre-admission to the hospital. This study was divided into an experimental group receiving smart bracelets and a control group receiving conventional treatment. Both groups were randomized using a random number table. The primary variables of this study were as follows: time to first administration of life-saving intervention, time to first administration of blood transfusion, time to first administration of hemostatic drugs, and mortality rates within 24 h and 28 days post-admission to the hospital. The secondary outcomes included the amount of time before trauma team activation and the overall length of patient stay in the emergency room., Results: The measurement results for both the emergency smart bracelet as well as traditional equipment showed high levels of consistency and accuracy. In terms of pre-hospital emergency life-saving intervention, there was no significant statistical difference in the mortality rates between both groups within 224 h post-admission to the hospital or after 28-days of treatment in the emergency department. Furthermore, the treatment efficiency for the group of patients wearing smart bracelets was significantly better than that of the control group with regard to both the primary and secondary outcomes of this study. These results indicate that this smart bracelet has the potential to improve the efficiency and effectiveness of trauma care and treatment., Conclusion: A body area network-based smart bracelet combined with remote 5G technology can assist the administration of emergency care to trauma patients prior to hospital admission, shorten the timeframe in which life-saving interventions are initiated, and allow for a quick trauma team response as well as increased efficiency upon administration of emergency care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Yuan, Li, Yang, Fang, Fan and Hou.)

Background: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear., Aim: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection., Methods: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound., Results: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups ( P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups ( P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups., Conclusion: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study aimed to investigate the relationship between chronotypes and aggression in adolescents., Methods: A cross-sectional study was conducted on 755 primary and secondary school students aged 11-16 years in rural areas of Ningxia Province, China. The Chinese version of the Buss-Perry Aggression Questionnaire (AQ-CV) and the Chinese version Morningness-Eveningness Questionnaire (MEQ-CV) were used to assess the aggressive behavior and chronotypes of the study subjects. The Kruskal-Wallis test was then used to compare the differences in aggression among adolescents with different chronotypes, and Spearman correlation analysis to determine the relationship between chronotypes and aggression. Further linear regression analysis was used to investigate the effects of chronotype, personality traits, family environment, and class environment on adolescent aggression., Results: There were significant differences in chronotypes between different age groups and different sexes. Spearman correlation analysis showed that the MEQ-CV total score was negatively correlated with the AQ-CV total score (r = -0.263) and score of each AQ-CV subscale. In Model 1, chronotypes were negatively associated with aggression when controlling for age and sex, and evening-type adolescents might be more likely to exhibit aggressive behavior (b = -0.513, 95% CI: [-0.712, -0.315], P < 0.001); in Model 2, the negative association remained after controlling for family and class environment on the basis of Model 1 (b = -0.404, 95% CI: [-0.601, -0.208], P < 0.001); and in Model 3, the negative association still existed after controlling for personality traits on the basis of Model 2 (b = -0.383, 95% CI: [-0.577, -0.190], P < 0.001)., Conclusion: Compared to morning-type adolescents, evening-type adolescents were more likely to exhibit aggressive behavior. Given social expectations for MT adolescents, adolescents should be actively guided to develop a good circadian rhythm that may be more conducive to their physical and mental development., (© 2023. The Author(s).)

Introduction: Functional magnetic resonance imaging (fMRI) has shown that aging disturbs healthy brain organization and functional connectivity. However, how this age-induced alteration impacts dynamic brain function interaction has not yet been fully investigated. Dynamic function network connectivity (DFNC) analysis can produce a brain representation based on the time-varying network connectivity changes, which can be further used to study the brain aging mechanism for people at different age stages., Method: This presented investigation examined the dynamic functional connectivity representation and its relationship with brain age for people at an elderly stage as well as in early adulthood. Specifically, the resting-state fMRI data from the University of North Carolina cohort of 34 young adults and 28 elderly participants were fed into a DFNC analysis pipeline. This DFNC pipeline forms an integrated dynamic functional connectivity (FC) analysis framework, which consists of brain functional network parcellation, dynamic FC feature extraction, and FC dynamics examination., Results: The statistical analysis demonstrates that extensive dynamic connection changes in the elderly concerning the transient brain state and the method of functional interaction in the brain. In addition, various machine learning algorithms have been developed to verify the ability of dynamic FC features to distinguish the age stage. The fraction time of DFNC states has the highest performance, which can achieve a classification accuracy of over 88% by a decision tree., Discussion: The results proved there are dynamic FC alterations in the elderly, and the alteration was found to be correlated with mnemonic discrimination ability and could have an impact on the balance of functional integration and segregation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Jelfs, Mahmoud, Neville and Fang.)

Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1 st to 3 rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2 nd to 3 rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2 nd and 3 rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management., (© 2021. The Author(s).)

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 10 4 cells/3 μL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,β-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca 2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,β-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,β-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province., Methods: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed., Results: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7 /αα (50.23%) and β IVS-II-654 /β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively., Conclusion: Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH., Competing Interests: The authors declare no conflicts of interest for this work., (Copyright © 2023 Yi-qi Ma et al.)

Talent team construction is the foundation of translational medicine research of acupuncture and moxibustion. In college education and continuing education after graduation, with the idea of translational medicine, it is necessary to cultivate both the ability of basic research and clinical skills for the students of traditional Chinese medicine, especially those majored in acupuncture and moxibustion, as well as train the acupuncture-moxibustion researchers who qualified with medical practitioner to contact with clinical practice, discover clinical scientific problems and research priorities, and engage in basic research at the same time. Acupuncture-moxibustion practitioners with higher education should be trained to be able to engage in basic and development researches on the premise of improving their clinical ability, so as to cultivate more translational research talents, build translational research team, and promote the pace of research and application of acupuncture-moxibustion translational medicine.

Inflammation and oxidative stress are among the leading causes of poor prognosis after peripheral nerve injury (PNI). Urolithin-A (UA), an intermediate product produced by the catabolism of ellagitannins in the gastrointestinal tract, has anti-inflammatory, antioxidant, and immunomodulatory properties for inflammation, oxidative damage, and aging-related diseases. Hence, we prepared UA-loaded hydrogels and embedded them in the lumen of PCL nerve guide conduits (NGCs). The hydrogels continuously released appropriate doses of UA into the microenvironment. Based on in vitro studies, UA facilitates cell proliferation and reduces oxidative damage. Besides, the experimental evaluation revealed good biocompatibility of the materials involved. We implanted NGCs into rat models to bridge the sciatic nerve defects in an in vivo study. The sciatic functional index of the PCL/collagen/UA group was comparable to that of the autograft group. Additionally, the consequences of electrophysiological, gastrocnemius muscle and nerve histology assessment of the PCL/collagen/UA group were better than those in the PCL and PCL/collagen groups and close to those in the autograft group. In this study, UA sustained release via the PCL/collagen/UA NGC was found to be an effective alternative treatment for PNI, validating our hypothesis that UA could promote regeneration of nerve tissue.

The process of acupuncture internationalization includes two basic stages: pre-internationalization period and post-internationalization period. The former is mainly characterized by unidirectional export led by China, while other countries and regions are mainly learning and absorbing. The latter is manifested by the localization transformation and development of acupuncture in foreign countries, which brings severe challenges to traditional Chinese acupuncture. It is helpful to grasp the international trend of acupuncture development by actively understanding the trajectory of acupuncture internationalization. To effectively cope with the challenges brought by the post-internationalization period, modern acupuncture is needed to be developed proactively. Only by establishing a modern acupuncture system compatible with modern science, can China continue to lead the international acupuncture academic development.

An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo . The results show that the NGCs have good biocompatibility in vitro . Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nan, Lin, Wang, Jin, Fang, Xu, Liu, Zhang, Wu, Zhou, Chen, Cao, Wang and Liu.)

Objective: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP., Methods: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection., Results: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection ( P <0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection ( P <0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection ( P <0.05, P <0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection ( P <0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection ( P <0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection ( P <0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased ( P <0.01)., Conclusion: The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.

Under the situation of the rapid expansion of hospital, the dilemma of acupuncture-moxibustion department, as well as the relevant solutions are explored. The main reasons for the shrinking situation of the service in acupuncture-moxibustion department include: the disease-based department division trends to divert many diseases suitably treated in acupuncture-moxibustion department; the environment pursuing economic benefits restricts the development of acupuncture-moxibustion therapy characterized by "simple and low-cost operation". There are three important approaches for breaking through the dilemma of acupuncture and moxibustion therapy. First, modifying the traditional service mode as waiting for patients in acupuncture-moxibustion department and promoting acupuncture and moxibustion technology to be adopted in other departments rather than limited only in acupuncture-moxibustion department. Second, increasing the charges of acupuncture and moxibustion technology rationally. Third, positioning accurately the role of acupuncture and moxibustion technology in health services based on its own characteristics and advantages and promoting it in community medical institutions. All of these solutions require the guidance of supporting policies.

Background: The neurodevelopmental model of obsessive-compulsive disorder (OCD) suggests that the neurodevelopmental changes in the ventral striatal circuit of the prefrontal lobe are associated with the initial symptoms of OCD. Facial morphology is one of the most consistent anatomical phenotypes of neurodevelopmental disorders, which can reflect brain structure and function. Facial deformity, an easily measured index of brain malformation, can reflect abnormal brain structure and function. Therefore, this study aims to explore the relationship between clinical features and neurodevelopment of adolescents with OCD through facial morphology., Methods: The enrolled study sample comprised 40 adolescents diagnosed with OCD using the Obsessive Compulsive Inventory-Child Version (OCI-CV) and 38 healthy controls (HCs). Facial photos, 21 facial diameters, and 9 facial angles were collected using image software., Results: In males, lower lip red height was significantly lower in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). In females, the nasolabial angle was smaller in OCD patients than in HCs (P < 0.025); no significant differences were observed in other facial indicators (all P > 0.025). The difference in lower lip red height between the OCD group and HC group was positively correlated with neutralizing symptoms (r = 0.401, P < 0.05)., Conclusions: Male OCD patients had a thinner lower lip and female OCD patients had smaller nasolabial angles. The facial features of adolescents with OCD were positively correlated with lower lip redness and neutralizing symptoms., (© 2021. The Author(s).)

The elements of ethical review related to clinical research of acupuncture and moxibustion is discussed to provide ideas for various institutions to carry out relevant ethical review. It is believed that the ethical review of clinical research of acupuncture and moxibustion needs to focus on the specificity of acupuncture and moxibustion. Starting from the basic theory of traditional Chinese medicine, the theory of meridians and acupoints and the theory of syndrome differentiation along meridians, the key contents of ethical review such as intervention methods, grouping design and placebo control should be considered, so as to standardize the clinical research of acupuncture and moxibustion and protect the health and rights and interests of participants.

Opiates produce a strong rewarding effect, but abstinence from opiate use emerges with severe negative emotions. Depression is one of the most frequent emotion disorders associated with opiate abstinence, which is thought to be a main cause for relapse. However, neurobiological bases of such an aversive emotion processing are poorly understood. Here, we find that morphine abstinence activates κ-opioid receptors (KORs) by increasing endogenous KOR ligand dynorphin expression in the amygdala, which in turn facilitates glutamate transporter 1 (GLT1) expression by activation of p38 mitogen-activated protein kinase (MAPK). Upregulation of GLT1 expression contributes to opiate-abstinence-elicited depressive-like behaviors through modulating amygdalar glutamatergic inputs to the nucleus accumbens (NAc). Intra-amygdala injection of GLT1 inhibitor DHK or knockdown of GLT1 expression in the amygdala significantly suppresses morphine-abstinence-induced depressive-like behaviors. Pharmacological and pharmacogenetic activation of amygdala-NAc projections prevents morphine-abstinence-induced behaviors. Overall, our study provides key molecular and circuit insights into the mechanisms of depression associated with opiate abstinence., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, many studies have confirmed the positive effect of acupuncture and moxibustion in the treatment of irritable bowel syndrome (IBS), and a lot of researches have been made to explore its neurobiological mechanisms. The neurobiological mechanisms include two aspects 1) remission of visceral hypersensitivity via peripheral and central pathways (spinal cord and brain), and 2) improvement of intestinal motility via vagus nerve and enteric nervous system (ENS)- interstitial cells of Cajal (ICC)-smooth muscle cells (ENS-ICC-SMC) network, and 5-HT, vasoactive intestinal peptide (VIP), neuropeptide Y, etc.. At the same time, we also discussed the existing problems in the research of the underlying neurobiological mechanisms of acupuncture and moxibustion for IBS. The existing problems in this field mainly include 1) fragmentization or lack of integrity in researches, and 2) limitation of the reductionism method. For this reason, we should draw lessons from the research methods of systematic science to study the neurobiological mechanisms of acupuncture and moxibustion in the treatment of IBS, including the detailed links of peripheral and central nervous transmission of acupoint stimulation signals, and the interactive action modes (two-way benign regulation, multi-target regulation, saturation regulation, etc.).

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABA A R agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABA A R antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety., (© 2021. The Author(s).)

An auxiliary isolation device of cupping therapy for cross-infection prevention is designed to reduce the disinfection steps and be against cross transmission. This device is composed of a disposable isolation unit made of fire proof plastic material and a disposable cup-mouth fixator made of elastic material. The disposable isolation unit includes two parts, the cup neck isolation unit and the inner isolation unit of fire cup. These two parts connect with the disposable cup-mouth fixator. All of those three sections of the device are center-connected ring-like structure. This device can well prevent the direct contact of fire cup with the patient's skin surface, characterized as safety protection, simple operation and saving time and manpower.

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073 wt ) and LPS-induced in vitro NETosis with CFT073 wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.

Objective: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine., Methods: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards., Results: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [ MD =-0.31, 95% CI :-0.49--0.13, P= 0.0006]; ②the adjuvant therapy with moxibustion improved lung function significantly [FEV1% ( MD =4.00, 95% CI: 2.63-5.37, P <0.000 01) and FEV1/FVC ( MD =3.56, 95% CI :1.69-5.43, P =0.000 2)]; ③the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) ( MD =35.00, 95% CI :18.02-51.99, P <0.000 1); ④the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly ( MD =-0.62, 95% CI :-1.18--0.05, P =0.03); ⑤no adverse reaction was reported in the included literature., Conclusion: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase., Competing Interests: The authors have declared that no competing interests exist.

It is to determine the effect mechanism and therapeutic method of the idea as "guiding meridian sinew qi along with meridian running course" for meridian sinew disorders so as to provide the reference for clinical treatment of these disorders. "Guiding meridian sinew qi along with meridian running course" is the summary for the approach to meridian sinew disorders by YANG Shang - shan , recorded in Huangdi Mingtang Jing ( The Yellow Emperor's Acupoints Canon of Mingtang ), but the concrete statement on it had been lost. By investigating the existing ancient works, the authors discussed the specific meaning of jinqi (meridian sinew qi ), the relationship between jingjin (meridian sinew) and jingmai (meridian), the method of "guiding meridian sinew qi along with meridian running course" and its preferable acupoint selection for treatment of meridian sinew disorders with both the primary and the secondary considered.

Background: Since the 1990s, families from the ecologically hostile mountainous southern areas of Ningxia Province, China, have been migrating to the northern areas of the province. This study compared the prevalence of behavioral problems among migrant adolescents to those among host adolescents (adolescents from the northern areas) and adolescents in the region of origin (adolescents from the southern areas), to determine whether ecological migration is related to adolescent behavioral problems, and possible changes in such problems over time., Methods: We used the Children and Adolescents Ecological Migration Survey on Mental Health, administered to 4805 students aged 12-16 years and their parents between 2012 and 2014 (W1), of whom 1753 students and their parents completed the follow-up between 2014 and 2017 (W2). Parents answered questions related to adolescent behavioral problems, main source of family income, parents' desire to reverse migrate, improved standard of living, and parents' educational attainment, while children completed the Eysenck Personality Questionnaire and a classroom environment questionnaire., Results: The prevalence of behavioral problems among the migrant adolescents (28.04%) was significantly higher than among host adolescents (21.59%) or adolescents in the region of origin (24.37%; p < 0.001) at W1. After adjusting for gender and age, parents' work outside the home was the main source of family income (OR = 1.42, 95% CI = 1.13-1.78), and adolescents' learning burden (OR = 1.04, 95% CI = 1.01-1.06) in school negatively influenced behavioral problems. Strong student-teacher relationships (OR = 0.97,95% CI = 0.94-0.99) and parents who had no intention to move back to the original residence (OR = 0.70, 95% CI = 0.52-0.94) exerted a protective effect at W1; at W2, a protective effect was associated with improved living conditions (OR = 0.39-0.55, 95% CI = 0.25-0.84). The extent of behavioral problems among migrant adolescents significantly decreased after two years., Conclusion: Ecological migration will increase children's behavioral problems in the early stage, with various factors influencing the extent of these problems.

Background: This study aimed to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on bone metastasis pain, anxiety and immune function in cancer patients., Methods: A total of 127 patients with bone metastasis pain from malignant tumors were treated with TEAS or drugs. The TEAS group comprised of 62 patients, while the drug control group comprised of 65 patients. The differences in general indexes, baseline pain and anxiety between these two groups were not statistically significant., Results: Compared with those before treatment, the visual analog scale (VAS) scores of patients in the TEAS group and drug control group decreased after treatment, and the differences were statistically significant. The degrees of pain relief after treatment were similar between the two groups. Anxiety improved in both the TEAS group and drug control group, and the difference between these two groups was not statistically significant. The differences in immune indexes, B cell and CD8 between the TEAS group and drug control group were statistically significant. TEAS treatment could improve the declining trend of CD8 in patients., Conclusions: TEAS treatment and drug treatment can effectively alleviate mild to moderate pain in patients, and the efficacy of these two groups is similar. The treatment for moderate and severe pain needs to be combined with drug treatment to achieve a control effect. TEAS can improve the anxiety and immune function of patients, and prevent the decrease in B cells and CD8 in patients treated with drugs alone.

On the base of the relevant theories on disease identification of western medicine and traditional Chinese medicine, professor FANG Jian - qiao has made the differentiation of cranial tinnitus and proposes the intervention measures. The location of disease is identified firstly. Secondly, the deficiency is distinguished from the excess, and the involved zangfu organs are determined as well. In view of the holistic idea and in combination of meridian differentiation of acupuncture-moxibustion, the principle of treatment is proposed, named "regulating qi , harmonizing blood circulation, clearing office and tranquilizing the mind". In treatment, the disease is treated individually. According to the involved location of onset and the related meridian running course, acupuncture-moxibustion therapy is exerted, in which, the local acupoints are combined with the distal ones. Additionally, electroacupuncture is used flexibly. The appropriate electric wave and frequency are selected in consideration of the syndromes/patterns of disease so as to optimize the regimen of acupuncture-moxibustion therapy. All of the approaches aforementioned provide the reference to clinical treatment of traditional Chinese medicine.

The specific therapeutic regimen of Bell's palsy was proposed in association with the common refractory factors and the clinical experience of professor Fang Jian - qiao . It is viewed that aging, absent intervention standard treatment at early stage, no prodromal symptoms and progressive onset are the refractory factors. Acupuncture at the local area is predominated in treatment. The different acupoint prescription regimens of acupuncture therapy are selected depending on muscle relaxation, muscle stiffness and specific accompanying symptoms, associated with electric stimulation, moxibustion and the tapping technique with plum-blossom needle so as to ensure the improvement of clinical therapeutic effect.

Dysosmia affects not only odour identification, but also memory, appetite, immunity and affection. Moreover, it suggests the occurrence of some diseases. The etiology of dysosmia is various and the treatment with western medicine is limited. In this paper, by analyzing the relevant research articles on olfactory disorders treatment with acupuncture and moxibustion, the clinical application of acupuncture and moxibustion, the thought of its diagnosis and treatment as well as relevant effect mechanism were explored. It is anticipated to provide the clinical physicians with the references to the treatment of dysosmia.

Objective: To observe the direct intervention effects of electroacupuncture (EA) and non-steroid anti-inflammatory drugs (NSAIDs) on pain memory, and to explore their effects on cAMP/PKA/cAMP pathway in anterior cingulate gyrus (ACC)., Methods: Fifty clean healthy male SD rats were randomly divided into a control group, a model group, an indomethacin group, an EA group and a sham EA group, 10 rats in each group. Except the control group, the pain memory model was established in the remaining four groups by twice injection of carrageenan at foot; 0.1 mL of 2%λ-carrageenan was subcutaneously injected at the left foot of rats; 14 days later, when the pain threshold of rats of each group returned to the basic level, the second injection was performed with the same procedure. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36) for 30 min; the rats in the indomethacin group was treated with indomethacin intragastric administration with the dose of 3 mg/kg; the rats in the sham EA group was treated with EA without electricity at the point 0.3 mm forward "Zusanli" (ST 36) with the depth of 2 mm for 30 min; the rats in the control group was not given any invention. All the above interventions were performed 5 h, 1 d, 2 d and 3 d after the second injection of 2% λ-carrageenan. The left-side paw withdrawal thresholds (PWT) were observed before the first injection, 4 h, 3 d, 5 d after the first injection, before the second injection and 4 h, 1 d, 2 d, 3 d after the second injection. Three days after the second injection, the number of positive cells of cAMP, p-PKA, p-CREB and the number of positive cells of protein co-expression in the right ACC brain area were detected by immunofluorescence, and the relative protein expression of p-PKA and p-CREB were detected by Western blot., Results: Compared with the control group, the PWTs in the model group decreased significantly 4 h, 3 d and 5 d after the first injection and 1 d, 2 d and 3 d after the second injection ( P <0.05); compared with the control group, the positive expression of cAMP, p-PKA and p-CREB in the right ACC brain area in the model group increased significantly ( P <0.05), and the number of positive cells of the co-expression of cAMP/p-PKA and p-PKA/p-CREB also increased significantly ( P <0.05). Compared with the model group, indomethacin group and sham EA group, the PWTs in the EA group were increased significantly 1 d, 2 d and 3 d after the second injection ( P <0.05); compared with the model group, indomethacin group and sham EA group, the positive expression of p-PKA and p-CREB in the right ACC brain area in the EA group decreased significantly ( P <0.05), and the number of positive cells of co-expression of cAMP/p-PKA and p-PKA/p-CREB was decreased significantly ( P <0.05). Compared with the model group and sham EA group, the positive expression of cAMP in the right ACC brain area was decreased in the EA group ( P <0.05)., Conclusion: EA have a direct intervention effect on pain memory, which have significant advantage over NSAIDs in the treatment of chronic pain. The advantage effect of EA on pain memory may be related to the inhibition of cAMP/PKA/CREB pathway in ACC area.

Objective: To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism., Methods: A total of 35 SD rats were randomized into a sham BCP group ( n =6), a BCP group ( n =7), a MT group ( n =7), a BNA+EA group ( n =8) and a shame BNA group ( n =7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot., Results: Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group ( P <0.01). Eleven days after the operation, the PWT of the MT, BNA+EA and sham BNA groups was increased compared with the BCP group ( P <0.01). Twenty-two days after the operation, the difference was no significant between the BCP group and MT group ( P >0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group ( P <0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group ( P <0.05, P <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group ( P <0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group ( P <0.01, P <0.05), while the level of MOR was increased ( P <0.01)., Conclusion: Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.

Objective: To observe the effect of bone-edge electroacupuncture (EA) intervention on mechanical pain threshold (PT) and expression of G protein-coupled receptor kinase (GRK5), β-arrestin 2, total and phosphorylated PKC alpha (p-PKCα) proteins in the locus coeruleus (LC) of rats with bone cancer pain induced morphine tolerance, so as to reveal its partial central mechanisms underlying pain relief., Methods: Forty SD rats were randomly divided into 5 groups, namely sham bone cancer, bone cancer pain, morphine tolerance, bone-edge EA, and sham EA ( n ＝ 8 rats in each group). The bone cancer with morphine tolerance model was established by intramedullary injection of MRMT-1 cells into the tibial cavity, and then intraperitoneal injection of morphine hydrochloride injection. After successful establishment of morphine tolerance model, the bone-edge EA (2 Hz/100 Hz，0.5－1.5 mA) was applied to bilateral "Zusanli" (ST36) and "Kunlun" (BL60) for 30 min, once a day for 7 days, after inserting the needle-tip to the tibial bone surface. The ipsilateral mechanical paw withdrawal thresholds (PWTs) were detected dynamically. The expression levels of GRK5, β-arrestin 2, PKCα and p-PKCα in the LC area were measured by Western blot., Results: The PWTs of bone cancer pain rats were decreased on day 10 after inoculation of cancer cells ( P <0.01). After i．p. of morphine for 11 days, no analgesic effect and pain tolerance appeared ( P >0.05). The PWTs were significantly increased in the bone-edge EA intervention group ( P <0.01), not in the sham EA group ( P >0.05). In comparison with the sham bone cancer group, the expression of GRK5 protein in morphine tolerance group was significantly decreased ( P <0.01); compared with morphine tolerance group, the expression of GRK5 protein in bone-edge EA group was increased( P <0.01). In comparison with the sham bone cancer group, the expression of β-arrestin 2 and p-PKCα in bone cancer group significantly increased ( P <0.01). After the intervention, the increased β-arrestin 2 and p-PKCα expressions were reversed in the bone-edge EA group ( P <0.01); compared with morphine tolerance group and sham EA group, the expression of PKCα protein was decreased( P <0.01)., Conclusion: Bone-edge EA can effectively relieve morphine tolerance in bone cancer pain rats, which may be related to its functions in up-regulating GRK5 protein and down-regulating β-arrestin 2, PKCα and p-PKCα proteins in LC.　.

Objective: To observe the expression of GABA A receptor mRNA in different brain regions of the central nervous system in chronic inflammatory pain rats and the intervention effect of electroacupuncture (EA)., Methods: A total of 48 SPF male SD rats were randomly divided into a blank control group, a model control group, an EA group and a sham EA group, 12 rats in each group. The model of chronic inflammatory pain was established by injecting Freund's complete adjuvant into the foot. The EA group was treated with EA 28 days after the model establishment. The "Housanli" (ST 36) and "Kunlun" (BL 60) were selected and treated with dilatational wave, 2 Hz/100 Hz in frequency, 0.5-1.5 mA for 30 min; EA was given only once. In the sham EA group, the same acupoints were selected but the needles were only inserted into subcutaneous area; EA was connected for 30 min without electrical stimulation. The behavior changes of mechanical pain threshold and thermal pain threshold before model establishment, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after the model establishment as well as emotional behavior 29 days after the model establishment were observed; the relative expressions of GABA A receptor mRNA in anterior cingulate cortex, amygdala and hypothalamus were observed., Results: Compared with the blank control group, the change rates of mechanical pain threshold and thermal pain threshold in the model control group were decreased significantly 1 day, 3 days, 7 days, 14 days, 21 days, 28 days after model establishment ( P <0.01); 29 days after model establishment, the movement distance and staying time in the central area of open field test in the model control group were decreased significantly ( P <0.05). After EA intervention, compared with the model control group and the sham EA group, the change rates of mechanical pain threshold and thermal pain threshold, as well as the movement distance and the staying time of central area were significantly increased in the EA group ( P <0.01, P <0.05). Twenty-nine days after model establishment, the expression of GABA A receptor mRNA in anterior cingulate cortex and hypothalamus was not significantly different among all groups ( P >0.05). Compared with the blank control group, the expression of GABA A receptor mRNA in the amygdala was decreased significantly in the model control group ( P <0.01); compared with the model control group and the sham EA group, the expression of GABA A receptor mRNA in amygdala was increased after intervention in the EA group ( P <0.01)., Conclusion: Single treatment of EA could significantly increase the mechanical pain threshold and thermal pain threshold, improve abnormal emotional behavior in rats with chronic inflammatory pain, which may be related to the increasing of expression of GABA A receptor mRNA in the amygdala.

To reveal the distribution characteristics of carbon, nitrogen and phosphorus in the sediments of Zhushan Bay at Taihu Lake, sedimentary columns were collected and sliced by 2 cm vertically from ten sampling points in three sections of Zhushan Bay. The content of total nitrogen (TN), total phosphorus (TP), and total organic carbon (TOC) were determined for each slice to reveal their horizontal and vertical distribution. The results showed that:spatially, the content of TN, TP, and TOC increased in the surface sediments of Zhushan Bay from the open lake area to the bay, and inside the bay these indexes were significantly higher than in the open lake area ( P <0.01). The content of TN, TP, and TOC in the surface sediments in the bay (section A) were 1.53 mg·g -1 , 1.55 mg·g -1 , and 11.31 mg·g -1 , respectively, while in the surface sediments near the open lake (section C) they were only 0.75 mg·g -1 , 0.57 mg·g -1 , and 6.70 mg·g -1 , respectively. Vertically, a feature of surficial enrichment was shown, and the contents of carbon, nitrogen and phosphorus in all three sections showed a decreasing trend with increase of depth. The contents of TN, TP and TOC in the surface sediments are 2-3 times, 2-5 times, and 2-3 times those in the bottom sediments, respectively. Generally, the average TP content in the sediment of Zhushan Bay is 0.93 mg·g -1 , suggesting an apparent heavy pollution, while the average TN content is 1.11 mg·g -1 as slight pollution. According to the organic nitrogen index and comprehensive pollution index, the northern part of Zhushan Bay is suffering from heavy pollution, where the organic pollution is relatively strong. The TP pollution index is between 1.03 and 3.87, indicating heavy pollution in Zhushan Bay.

Objective: The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center., Methods: Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group ( n  = 62) and the control group ( n  = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention., Results: After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly ( P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly ( P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant ( P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively)., Conclusion: A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Li-wan Zhang et al.)

In shallow eutrophic lakes, benthic bioclastic deposits accumulate abundant organic carbon derived from macrophyte detritus. Taking the typical macrophyte-dominated Xukou Bay as the study area, field investigations were performed using sediment cores to evaluate benthic phytodetritus accumulation. Specifically, nutrient contents, TOC/TN ratios, pigmentation, and biodegradable compounds were measured as descriptive parameters. The results show that the benthic bioclastic deposit had accumulated abundant pigments, nutrients, and biodegradable compounds derived from macrophytes detritus. These were mainly localized in the top 15 cm of sediments. Nitrogen loading in the sediments was significantly higher than phosphorous loading, with a distinct spatial difference; the total nitrogen content ranged from 127.2-2092.8 mg·kg -1 and total phosphorous content ranged from 222.1-528.4 mg·kg -1 . Moreover, nitrogen loading (1033.6 mg·kg -1 ) in the vegetated zones were higher than in the unvegetated zones (325.2 mg·kg -1 ). In addition, carbohydrate (3.7 mg·g -1 ) was the dominant component of sedimentary bioclastic material, with lipids (2.8 mg·g -1 ) being the second most abundant of the biodegradable compounds. The major sources of nutrients and biodegradable compounds in the sediment were massive aggregates of macrophyte detritus. The pigment, nutrient, and biodegradable compound contents in the vegetated zones were significantly higher than in unvegetated zones ( P <0.01). The benthic eutrophic state showed a trend from mesotrophic to eutrophic in Xukou Bay, which should be given more attention in the future management of freshwater lake ecosystems.

Background: Acupuncture stimulation at GV26 during the acute phase of cerebral ischaemia can effectively reduce brain damage induced by ischaemic injury. However, the time course of the effects of acupuncture stimulation has not yet been thoroughly studied., Objective: To investigate the effects of manual acupuncture (MA) on glutamic acid (Glu) and γ-aminobutyric acid (GABA) expression in the cerebrospinal fluid of rats with middle cerebral artery occlusion (MCAO) and determine whether there is a temporal effect of acupuncture on the treatment of cerebral ischaemia., Methods: We performed thread occlusion of the right middle cerebral artery in rats to establish an animal model of MCAO. Simultaneously, during acupuncture treatment, microdialysis was used to continuously and dynamically observe immediate alterations in amino acid metabolism with acupuncture stimulation after cerebral ischaemia in vivo in this rat model of MCAO., Results: We found that, in comparison with an untreated MCAO group, Glu content was significantly decreased during the first acupuncture stimulation and during the course of the acupuncture treatment in the MCAO+MA group (MCAO vs MCAO+MA: day 1, P=0.032; day 2, P=0.021; day 3, P=0.017). These findings were also seen after the end of treatment when acupuncture was no longer applied (MCAO vs MCAO+MA: day 7, P=0.009). Measurements of GABA content following cerebral ischaemic injury showed that GABA peaks 24 hours after damage, falls thereafter and decreases to baseline levels on day 7. In the MCAO+MA group, GABA content on days 1 to day 2 was lower than in the MCAO group (MCAO+MA vs MCAO: day 1, P=0.003; day 2, P=0.001), although it was higher than in the control group (MCAO+MA vs control: day 1, P=0.024; day 2, P=0.009). GABA content on day 3 and day 7 was higher in the MCAO+MA group than in the MCAO group and the control group (MCAO+MA vs MCAO: day 3, P=0.008; day 7, P=0.013; MCAO+MA vs control: day 3, P=0.002; day 7, P=0.009)., Conclusion: Acupuncture stimulation at GV26 can effectively decrease excessive release of Glu induced by ischaemia and maintain the endogenous inhibitory activity of GABA. This phenomenon was seen during the entire course of acupuncture treatment and continued for some time after the end of acupuncture treatment.