Molecular profile-based recommendations for postoperative adjuvant therapy in early endometrial cancer with high-intermediate or intermediate risk: a Chinese randomized phase III trial (PROBEAT).

BACKGROUND: The use of molecular categorisation is shifting paradigm towards the use of molecular information to refine risk stratification in endometrial cancer (EC). To date, evidence to support molecular-guided therapies is limited to retrospective studies and secondary molecular analyses of patients receiving standard treatment. The PROBEAT study is the first randomized phase III trial to evaluate tailored adjuvant treatment based on WHO-endorsed molecular classification in Chinese EC patients. It is expected to provide a clinical decision-making tool for adjuvant treatment of patients with high-intermediate risk (HIR) or intermediate risk (IR) EC to better optimise and personalise patient care and increase relapse-free survival. METHODS: The PROBEAT trial is a prospective, multicentre study led by Women's Hospital of Zhejiang University Gynaecologic Oncology Group. Recruitment started on January 24, 2022, and 590 patients with HIR or IR endometrioid EC are expected to be recruited from 13 clinical centres in China. All tumor tissues will be classified into four molecular subtypes (POLEmut, MMRd, p53abn, or NSMP) based on WHO-endorsed molecular classification. Patients will be randomly assigned at a 2:1 ratio to either experimental arm and will receive molecular profile-based adjuvant treatment (observation in the POLEmut subgroup, vaginal brachytherapy in the MMRd or NSMP subgroup, or chemoradiotherapy in the p53abn subgroup) or to standard arm and will receive preferred adjuvant radiotherapy as recommended by the recent National Comprehensive Cancer Network guidelines version 1 (2022). The primary outcome is 3-year rates of recurrence. Secondary outcomes are relapse-free survival, overall survival, adverse events and health-related cancer-specific quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05179447.

Clinical observation of acupuncture combined with modern rehabilitation in the treatment of limb motor dysfunction after ischemic stroke: A randomized controlled trial.

BACKGROUND: Motor dysfunction is a common sequela of ischemic stroke. This study aimed to explore the effective treatment of ischemic stroke by combining acupuncture and modern rehabilitation training. METHODS: This study was a single-center, randomized controlled clinical trial conducted at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, 90 cases were finally included, divided into 45 cases each in the body acupuncture group and the head acupuncture group. INTERVENTIONS: Both groups received basic drug treatment, modern rehabilitation training, and basic life care guidance; the body acupuncture group was treated with reference to acupuncture points from the classic textbook of acupuncture and moxibustion, and the head acupuncture group was given Zhu's scalp acupuncture treatment based on the body acupuncture group. Primary outcome index: unassisted muscle strength grading scale; secondary outcome index: assessment of activities of daily living; simplified Fugl-Meyer motor function rating scale. RESULTS: The Barthel scale score, Manual Muscle Testing scale score (upper and lower limbs), and simplified Fugl-Meyer scale score (upper and lower limbs) in the 2 groups were improved (P ≤ .05), and the efficacy of the head-acupuncture group was better than that of the body-acupuncture group (P ≤ .05); there was no significant improvement in the simplified Fugl-Meyer scale (hand) score in both groups (P ≥ .05). There was no significant improvement in these scores (P ≥ .05). The difference in efficiency between the 2 groups was not statistically significant (P ≤ .05), and the apparent efficiency in the cephalic needle group was higher than that in the body needle group (P ≤ .05). CONCLUSIONS: Simultaneous treatment with Zhu's scalp acupuncture and body acupuncture combined with modern rehabilitation training can significantly improve limb motor function in patients with ischemic stroke, and its efficacy is better than that of body acupuncture alone combined with modern rehabilitation training.

[YANG Jun's clinical experience of acupuncture for oculomotor paralysis].

Professor YANG Jun's clinical experience of acupuncture and moxibustion for oculomotor paralysis is summarized. Professor YANG Jun pays attention to disease differentiation and syndrome differentiation in the treatment of this disease. According to the characteristics of oculomotor paralysis, "early diagnosis and seeking treatment from the source" is advocated. According to the etiology and pathogenesis, professor YANG divides oculomotor paralysis into three types: the syndrome of wind-evil attacking collaterals, the syndrome of spleen-stomach weakness and the syndrome of qi-deficiency and blood-stasis. As such, the acupoints are selected according to syndrome differentiation, and several different acupuncture methods (pricking needling at eyelids, penetrating needling and lifting eyelids and contralateral- balance needling on the healthy side) are adopted to improve the symptoms of oculomotor paralysis. It is also suggested to use the combination of scalp acupuncture and electroacupuncture to achieve the best dose-effect state. Moreover, local stimulation around the eyes is important to achieve the effects of "qi reaching affected area".

[Electroacupuncture improves learning-memory ability by down-regulating expression of hippocampal Aß1-42 and Tau and NF-κB proteins in diabetic rats with cognitive impairment].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the expression of nuclear transcription factors κB (NF-κB) and Tau protein and content of amyloid (Aß) in diabetic rats with cognitive impairment, so as to explore its mechanism underlying improvement of learning-memory ability. METHODS: Male SD rats were randomly divided into normal control (n=9), model (n=9) and EA (n=9) groups. The diabetic mellitus model was established by feeding the rats with high fat and high sugar for 1 month and intraperitoneal injection of STZ (25 mg·kg-1·d-1) for 2 days. EA was applied to "Zusanli"(ST36) and "Neiting"(ST44) for 20 min, alternatively on both side every day, and "Yishu"(EX-B3) was stimulated by twirling the acupuncture needle with uniform reinforcing-reducing method for 1 min, followed by retaining it for 20 min. The treatment was conducted 6 times a week for 4 weeks. The learning-memory ability was evaluated by using Morris water maze swimming test. The blood glucose level was randomly detected by using a glucometer, the content of Aß1-42 in the hippocampal tissue was detected by ELISA, and the relative expression levels of hippocampal Tau and NF-κB p65 proteins and mRNAs were determined by Western blot and fluorescence quantitative real-time PCR, separately. RESULTS: After modeling, the blood glucose, escape latency, Aß1-42 content and the expression levels of Tau and NF-κB p65 proteins and mRNAs in the model group were significantly increased (P<0.01, P<0.05) in comparison with the normal control group. Following EA intervention, the modeling induced increase of blood glucose, escape latency, Aß1-42 content and the expression levels of Tau and NF-κB p65 proteins and mRNAs were reversed (P<0.05, P<0.01). CONCLUSION: EA can improve the learning-memory ability in rats with diabetic cognitive impairment, which may be related to its function in down-regulating the levels of hippocampal Aß1-42, Tau and NF-κB proteins.

[Effect of electroacupuncture invention on activities of PGC-1α/Irisin (FNDC5)/BDNF signaling in cerebral cortex, hippocampus and muscles in focal cerebral ischemic/reperfusion injury rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on the expression of peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC-1α), Irisin and brain-derived neurotrophic factor (BDNF) in the ischemic peripheral cortex, hippocampus and local skeletal muscle in rats with focal cerebral ischemic/reperfusion injury (CI/RI), so as to explore its underlying mechanism of improving of CI/RI. METHODS: Male SD rats were randomly divided into 3 groups: sham-operation, model and EA (11 rats in each group). The focal CI/RI model was established by middle cerebral artery occlusion (MCAO). EA (2 Hz /15 Hz, 2 to 4 mA) was applied to "Quchi" (LI11) and "Zusanli" (ST36) of the affected side for 20 min, once a day for 7 days. Zea-Longa's score and Balance Beam score were used to evaluate the neurological and motor functions. The infarcted volume of the brain was detected by using 2,3,5-triphenyltetrazolium chloride staining. The expression levels of PGC-1α, fibronectin type III domain-containing protein 5(FNDC5) and BDNF proteins in the ischemic peripheral cortex, hippocampus and local skeletal muscle were detected by Western blot. RESULTS: Compared with the sham-operation group, the Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume were notably increased (P<0.01), while the expression levels of PGC-1α, FNDC5 and BDNF proteins in the cerebral cortex and hippocampus (not in the local muscle) were significantly down-regulated in the model group (P<0.01, P<0.05). In comparison with the model group, the increase of Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume, and the decrease of expression levels of PGC-1α, FNDC5 and BDNF proteins in the ischemic peripheral cortex and that of BDNF in the hippocampus were reversed in the EA group (P<0.01, P<0.05). No significant changes were found in the expression levels of hippocampal PGC-1α and FNDC5 proteins in the hippocampus and those of PGC-1α, FNDC5 and BDNF proteins in the local muscle after EA intervention (P>0.05). CONCLUSION: EA can improve neurological and motor functions and reduce cerebral infarction volume in CI/RI rats, which may be related to its functions in activating PGC-1α/Irisin(FNDC5)/BDNF pathway in the cerebral cortex.

[Professor YANG Jun's experience in treatment of refractory facial paralysis based on acupuncture manipulation].

To summarize professor YANG Jun's experience in treatment of refractory facial paralysis by different acupuncture manipulation. Professor YANG Jun believes that refractory facial paralysis has prolonged course, qi and blood deficiency and collaterals injury after a long illness, and it is difficult to obtain obvious curative effect with routine acupuncture. Aimed at the etiology, pathogenesis and characteristics of disease, professor YANG Jun adopts 3 kinds of acupuncture manipulations, such as "penetration needling with long needle" "pulling technique exert after needle stuck" "contralateral-balance needling on the healthy side", to relieve deviation.

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

OBJECTIVE: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats. METHODS: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke. RESULTS: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p>0.05). CONCLUSION: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain.

INTRODUCTION: Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture. METHODS: In 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well. RESULTS: For PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture. DISCUSSION: Our study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

Enriched Environment Promotes Cognitive Function Recovery following Cerebral Ischemic Injury via Upregulating GABAergic and Glutamatergic Systems in the Contralateral Hippocampus.

Poststroke cognitive impairment severely affects the long-term recovery of patients. However, it remains unknown whether an enriched environment can remodel contralateral hippocampal function and promote cognitive function recovery after cerebral ischemic injury. To further explore, 36 C57BL/6 mice that underwent permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to three groups: enriched environment (EE), standard condition (SC), and sham surgery (Sham). After 21 days of intervention, the Morris water maze and step-through test was utilized for testing the cognitive function of the mice, cresyl violet staining for measuring the degree of atrophy in the hippocampal tissues, and western blotting for quantitating the expression levels of GA1B, GAD67, and NR2B, and immunohistochemistry for levels of NR2B in the CA1 region of the contralateral hippocampus. The results showed that cognitive function-related behavioral performance decreased in the SC group, and performance was better in the EE group than that in the SC group (p < 0.01); no significant difference in the degree of contralateral cerebral atrophy was observed between the EE and SC groups (p > 0.05); levels of GA1B, GAD67, and NR2B in the contralateral hippocampus were significantly higher in the EE group than those in the SC group (p < 0.01); and the level of NR2B in the CA1 region of the contralateral hippocampus significantly increased in the EE group compared to the SC group (p < 0.01). We believe that contralateral hippocampal function is inhibited after cerebral ischemic injury, further affecting cognitive function. However, enriched environment can upregulate GABAergic and glutamatergic systems in the contralateral hippocampus to promote cognitive function recovery after cerebral ischemic injury.

[Clinical observation on therapeutic effect of moxibustion on cognitive decline in type 2 diabetes mellitus].

OBJECTIVE: To observe the effect of moxibustion on cognitive function in patients with cognitive decline of type 2 diabetes mellitus (T2DM). METHODS: A total of 47 patients with cognitive decline of T2DM were randomized into an observation group (24 cases, 4 cases dropped off ) and a control group (23 cases, 3 cases dropped off ). Conventional hypoglycemic intervention was adopted in the control group. On the basis of the treatment in the control group, Huayu Tongluo moxibustion (moxibustion for removing stasis and clearing collaterals) was applied at Baihui (GV 20), Dazhui (GV 14), Shenting (GV 24), once every 2 days, 4 weeks were as one course, totally 3 courses were required. Before and after treatment, scores of auditory verbal learning test (AVLT), complex figure test (CFT), Montreal cognitive assessment (MoCA) and trail making test-A (TMT-A) were observed in the both groups, and the clinical effective rates were compared. RESULTS: After treatment, the scores of immediate memory and delayed memory of AVLT in the observation group were higher than those before treatment and those in the control group (P<0.05). After treatment, the scores of visual space and executive function, delayed memory, attention and orientation of MoCA in the observation group were higher than those before treatment and those in the control group (P<0.05). The effective rate was 85.0% (17/20) in the observation group, which was superior to 10.0% (2/20) in the control group (P<0.05). CONCLUSION: Huayu Tongluo moxibustion has a definite effect on cognitive decline of type 2 diabetes mellitus.

Differences in Post-ischemic Motor Recovery and Angiogenesis of MCAO Rats Following Electroacupuncture at Different Acupoints.

BACKGROUND: Electroacupuncture (EA) can promote nerve and vascular regeneration, confer neuroprotection, inhibit apoptosis and inflammatory reactions, reduce oxidative stress injury, regulate neurochemicals and inhibit the formation of brain oedema in cerebral ischemic. However, the precise site of EA stimulation in the treatment of cerebral ischemic is unclear. OBJECTIVE: In the present study, we investigated the effect of EA at the acupoints of different meridians in motor function recovery and the involvement of Vascular Endothelial Growth Factor (VEGF), phosphorylated Protein Kinase B (P-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) and Platelet Endothelial Cell Adhesion Molecule-1(CD31) were examined in the peri-infarction cortex of rats. METHODS: The Middle cerebral artery occlusion (MCAO) model or sham surgery was performed in a total of Ninety male Sprague-Dawley rats. Rats were randomly divided into five groups: a sham group, a middle cerebral artery occlusion (MCAO) group, a Yang meridian group, a Yin meridian group and a combined Yang and Yin meridian group. EA stimulus was given during the middle cerebral artery occlusion. The neurobehavioural function was measured using Modified Neurological Severity Scores (mNSS), the rotarod test and the ladder rung walking test, and the protein expression of VEGF, P-Akt, p-eNOS in the peri-infarction cortex was detected by Western blot. Immunofluorescence was used to measure the vascular density of the peri-infarction cortex. RESULTS: EA at different meridian acupoints has no effect on the infarction volume, while EA at Yin meridian acupoints significantly promoted neurobehavioural functional recovery, increased the vascular density and enhanced protein kinase B/Endothelial nitric oxide synthase (Akt/eNOS) phosphorylation and VEGF expression. CONCLUSION: In the early stage of stroke, EA at Yin meridian acupoints can improve neurobehavioural functional recovery and the mechanism of this effect may be related to the enhanced expression of VEGF, P-Akt and p-eNOS in the peri-infarction cortex of rats.

Neuroprotective effect of electroacupuncture and upregulation of hypoxia-inducible factor-1α during acute ischaemic stroke in rats.

BACKGROUND: Acupuncture is a traditional method that has been widely used in various fields of medicine with therapeutic effect. However, evidence of effectiveness to support the application of electroacupuncture (EA) during the process of ischaemia is scarce. OBJECTIVES: To investigate dynamic changes in hypoxia-inducible factor (HIF)-1α expression as well as its association with neurological status in rats subjected to acute ischaemic stroke and EA intervention. METHODS: Forty adult male rats were randomly divided into three groups that received sham surgery (Control group, n=10) or underwent middle cerebral artery occlusion and EA (MCAO+EA group, n=15) or minimal acupuncture as a control treatment (MCAO+MA group, n=15). The rats in the MCAO+EA and MCAO+MA groups received EA or acupuncture without any electrical current, respectively, during 90 min of ischaemia. Rats in the Control group received the same surgical procedure but without MCAO. EA involved electrical stimulation of needles inserted into the quadriceps at 50 Hz frequency and 3 mA current intensity. Neurological status was evaluated on postoperative day 1, and cerebral infarction volume (IV) and HIF-1α expression 24 hours later. RESULTS: Neurological scores were improved and cerebral IV was decreased in the MCAO+EA group compared to the MCAO+MA group (both p<0.05). Moreover, HIF-1α expression was higher in the MCAO+EA group versus the MCAO+MA group (p<0.05). CONCLUSIONS: EA enhanced recovery of neurological function, decreased cerebral IV and increased HIF-1α expression in ischaemic rats. Further research is needed to determine whether EA is effective for stroke treatment through the stimulation of muscle contraction.