Perimenopausal anxiety and depression state fall under the categories of"visceral agitation"and"perimenopausal syndrome"in traditional Chinese medicine(TCM).Grounded in the theory of"Yang transforms qi,yin shapes form",this study posits that the pathogenesis of this condition is complex,often presenting with concurrent deficiency and excess syndromes,and is closely associated with yang deficiency-induced stagnation and qi stagnation leading to mental decline.The pathological mechanism is summarized as yang deficiency being the root and qi stagnation the manifestation.This article proposes a"yang-oriented treatment"approach for perimenopausal anxiety-depression disorders,employing a stepwise integrated acupuncture protocol termed"One Needling,Two Moxibustion,Three Consolidation":"One Needling"prioritizes regulating qi flow via acupuncture to soothe the liver and harmonize the spirit;"Two Moxibustion"utilizes refined moxibustion to warm yang,resolve stagnation,and activate yang circulation;"Three Consolidation"combines bloodletting therapy to remove stasis and regenerate tissues with intradermal needle embedding to stimulate yang and regulate visceral functions.This synergistic protocol aims to nourish the heart-mind,awaken the orifices of consciousness,alleviate perimenopausal anxiety and depressive symptoms,and consolidate therapeutic efficacy.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective:To explore the relationship between the Spike and the Gamma rhythm of the local field potential (LFP) in Alzheimer's disease (AD) transgenic mice during fear memory activity.Methods:Six-month-old APP/PS1/tau three transgenic (3xTg) mice and wild-type (WT) mice were divided into 3xTg group and WT group, with 10 mice in each group. The electrodes were embedded into the hippocampus of mice under sterile conditions, and the behavioral experiment of conditioned fear box test was carried out two weeks later. The changes of Gamma rhythm, Spike and Burst firing were recorded and analyzed by the wireless telemetry device which embedded in the mouse head. Finally, the correlation between Gamma rhythm and Spike was calculated by entropy value.Results:(1) In behavioral experiments, the freezing ratio caused by conditioned stimulation (CS) in 3xTg mice was ((54.07±2.32)%), which was significantly lower than that of WT mice ((76.21±2.88)%) ( t=4.796, P<0.01). (2) Simultaneously recorded the average power of the Gamma oscillation in the Pre-CS period of the WT mice was ((11.574±1.147) dB), which increased to ((18.108±1.177) dB) after CS ( t=3.386, P<0.01). After CS administration, the average power of Gamma in 3xTg group((12.346±1.345) dB) was significantly lower than that of WT group ( t=3.423, P<0.01). (3) The frequency of Spike release in WT mice during the Pre-CS period was ((5.667±1.475)times/s), significantly increased to ((11.008±1.335) times/s) after CS ( t=3.542, P<0.01). The frequency of Spike release of 3xTg mice after CS ((5.249±1.033) times/s) was significantly lower than that of WT group ( t=4.788, P<0.01). (4) The Burst duration of WT group in pre-CS and CS period were ((0.550±0.043)s) and ((1.075±0.034)s), respectively. It suggested that the Burst firing frequency of WT group increased significantly after conditional stimulation ( t=5.188, P<0.01). However, the release interval of 3xTg group after CS ((0.619±0.033)s) was significantly lower than that of WT group ( t=3.352, P<0.01). (5) After CS, the Spike-Gamma entropy curve of WT mice was always higher than that of 3xTg mice. The maximum correlation of WT group and 3xTG group were (0.403±0.031) and (0.314±0.028), respectively. The Spike-Gamma correlation of the 3xTg group was significantly lower than WT mice ( t=3.372, P<0.01). Conclusion:The defect of fear memory in Alzheimer's disease may be caused by the disharmony of Spike-LFP (Gamma) distribution.

Objective: To analyze the epidemiological characteristics and pathogen types of viral diarrhea in children under 5 years of age in Shandong province, and provide reference for the prevention and control of viral diarrhea. Methods: A total of 1 017 fecal samples were collected from all children aged 5 years and younger with diarrhea who were admitted to the sentinel hospital of Shandong province from 2012 to 2017 within 3 days. Rotavirus antigen was detected by using an ELISA method . Rotavirus G/P typing was performed by RT-PCR; Norovirus (GI and GII), Sapovirus, and Astrovirus were detected by multiplex RT-PCR, and adenovirus was detected by PCR. Results: In the 1 017 fecal specimens, the overall positive rate was 51.62% (525/1017), and viral nucleic acids were detected in at least 421 samples, and mixed virus infection was found in 104 sampes. The mixed infection accounted for 10.23% (104/1017) of all infections. The positive detection rates of Rotavirus, Calicivirus, Adenovirus and Astrovirus were 34.22% (348/1017), 16.91% (172/1017), 2.56% (26/1017), and 9.64% (98/1017)). The total detection rate of diarrhea virus and the detection rate of Rotavirus were the highest at 12 to 17 months of age, which was 51.72% (105/203) and 20.20% (41/203), respectively. The positive rate of diarrhea in children aged 2 years and younger was 49.36% (502/1017), which was much higher than the positive rate of diarrhea in children over 2 years old (2.26% (23/1017)). The peak of viral diarrhea was found to occur between November and April of the following year. The genotype of rotavirus was dominated by G9 (82.76%), the P genotype was dominated by P[8] (80.46%), and the G/P combination was dominated by G9P[8] (83.87%). Norovirus was the main infection in the Calicivirus (87.21%). Conclusions From 2012 to 2017, viral diarrhea in children under 5 years of age in Shandong Province was mainly caused by Rotavirus infection, followed by Norovirus. The overall prevalence of viral diarrhea in Shandong was moderate in China, and autumn and winter were the main epidemic season for viral diarrhea.

Objective To evaluate the clinical efficacy of oral ulcer protective agent in the prevention and treatment of oral mucositis in nasopharyngeal carcinoma (NPC) radiotherapy and its effect upon serum inflammatory factors.Methods A total of 90 patients diagnosed with nasopharyngeal carcinoma presenting with grade I oral mucositis caused by radiotherapy in our hospital were selected and randomly divided into two groups.In the experimental group,oral ulcer protective agent was given,and Kangfuxin gargle was administered in the control group.The incidence time and degree of radioactive oral mucositis,visual analogue scale (VAS) pain score,serum levels of CRP,TGF-β1,IL-6 and T lymphocyte subsets were statistically compared between two groups by independent-sample t-test.Results At 4 and 6 weeks after corresponding treatment,the incidence of grade Ⅱ and Ⅲ oral mucositis in the experimental group was significantly lower than that in the control group (P=0.018,0.021,0.027,0.014)).In the experimental group,the incidence of moderate and severe pain assessed by VAS was significantly lower compared with that in the control group (P=0.019,0.025);After corresponding treatment,the CRP levels in both groups were down-regulated and the CRP level in the experimental group was considerably lower than that in the control group (P=0.013).The levels of TGF-β1 and IL-6 in the control group were significantly increased (P=0.015、0.021),whereas dramatically declined in the experimental group (P=0.012,0.019).CD3(+),CD4 (+),CD8(+) and CD4(+)/CD8(+) were remarkably elevated in two groups,and more significant increase was observed in the experimental group (P=0.024,0.036,0.029,0.017).Conclusions Oral ulcer protective agent can effectively inhibit the progression of oral mucosal injury,shorten the healing time and relieve the pain of oral mucosal injury in patients with NPC.,which is worthy of clinical application.

Objective To investigate the clinical value of transumbilical single-port laparoscopic colorectal operation.Methods The clinical data of 25 patients with benign or malignant carcinoma at the upper part of the colon or rectum who were admitted to the No.4 People's Hospital of Zigong from January 2010 to December 2012 were retrospectively analyzed,and the clinical experience of transumbilical single-port laparoscopic colorectal operation was summarized.Surgical procedure was selected according to the position and nature of the lesion.Patients were followed up via out-patient examination and phone call till March 2013.Results Partial colorectal resection was done on 14 patients,radical resection of right colon on 1 patient,radical resection of transverse colon on 1 patient,radical resection of left colon on 1 patient,radical resection of sigmoid colon on 2 patients and radical rectectomy on 6 patients.The operation was successfully carried out on 22 patients,2 patients received four-port laparoscopic colorectal operation,and 1 patient was converted to open surgery.The median length of the incision of single-port laparoscopic colorectal operation was 3.8 cm (range,3.5-4.5 cm),and the operation time was (192 ± 32) minutes.The intraoperative blood loss was (61 ± 21)mL,and the median diameter of the tumor was 2.7 cm (range,1.0-5.0 cm).The median number of lymph nodes dissected was 7 (range,3-22),the mean time of postoperative anal exhaust time was 2 days (range,1-5 days),and the mean time of postoperative hospital stay was 8 days (range,6-20 days).The incidence of postoperative complications was 8.0％ (2/25),including 1 patient with wound infection and 1 patient with anastomotic leakage.The circumferential resection margins of radically resected specimens were negative in 11 patients.Twenty-two patients who received transumbilical single-port laparoscopic colorectal resection were followed up,and the median time of follow-up was 12 months.Colorectal liver metastasis was detected on 1 patient at postoperative month 10,and the other patients survived without tumor recurrence or metastases.Conclusions Transumbilical singleport laparoscopic colorectal operation is safe,micro-traumatic and feasible,and it also has less complication and good cosmetic effect.

BACKGROUND:Clinical limb ischemia-reperfusion with no reflow phenomenon after vascular injury repair seriously affects the prognosis of patients. Therapeutic effect of hyperbaric oxygen in myocardial ischemia reperfusion is exactly confirmed, but hyperbaric oxygen is rarely reported in the treatment of limb ischemia-reperfusion.
OBJECTIVE:To detect the expression of vascular endothelial growth factor and intracellular adhesion molecule 1 and to investigate the effect of hyperbaric oxygen on the prognosis of limb ischemia-reperfusion with no reflow phenomenon.
METHODS:By clinical screening, cases of main arterial injury of the limbs were selected and subjected to vascular repair for restoring limb blood supply. After surgery, al the cases were randomly divided into two groups (Combined treatment group and surgical group), 16 cases in each group. Combined treatment group was treated with hyperbaric oxygen combined with clinical anticoagulant, antiplatelet treatment;surgical group treated with only postoperative clinical treatment. Another 16 adult healthy volunteers were selected to receive hyperbaric oxygen as hyperbaric oxygen group. Expressions of vascular endothelial growth factor and intracellular adhesion molecule 1 were detected using enzyme-linked immunosorbent assay at 8, 72 hours and 7 days after surgery.
RESULTS AND CONCLUSION:In the combined treatment and surgical groups, patients exhibited higher expressions of vascular endothelial growth factor and intracellular adhesion molecule 1 than those in the hyperbaric oxygen group (P<0.01). After 72 hours, the expression of vascular endothelial growth factor was significantly higher in the combined
treatment group than the surgical group (P<0.01). At 8 and 72 hours, the expression of intracellular adhesion molecule 1 was lower in the combined treatment group than the surgical group (P<0.05). These findings suggest that hyperbaric oxygen can induce high expression of vascular endothelial growth factor and inhibit intracellular adhesion molecule 1, which is crucial for improving growth of blood capil ary, formation of endothelial cells, reducing no reflow phenomenon.

OBJECTIVE: To find out the clinical characteristics of Meniere's disease in flight aircrew and discuss relevant principles of clinical aviation medicine, in order to summarize experience in medical evaluation of aircrew. METHOD: Collect the data of 35 cases that were diagnosed with Meniere's disease from 1966 to 2011 in our hospital and analyze the clinical characteristics, diagnosis and flight conclusion of them. RESULT: Among the 35 cases, 34 patients complained of vertigo. 27 patients complained of tinnitus and 21 patients complained of hearing loss. (1) 18 cases manifested typical symptoms of Meniere's disease (paroxysmal vertigo, fluctuating neurosensory hearing loss, tinnitus and ear fullness); (2) 7 patients showed the symptoms of vertigo and tinnitus, not complaining of significant hearing loss (after inspection. 4 of them proved the low-frequency hearing loss); (3) 7 patients only manifested as vertigo; (4) 2 patients manifested as tinnitus and hearing loss. 1 patients manifested only hearing loss. On the basis of the diagnostic criteria of Meniere's disease formulated hy Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery. 22 patients were diagnosed with definite Meniere's disease, 2 patients were diagnosed with probable Meniere's disease, 11 patients were diagnosed with possible Meniere's disease. For patients with definite Meniere's disease and probable Meniere's disease, the phases of the disease were: 11 cases of phase I, 7 case of phase II and 6 case of phase III. The flight conclusion of all the 35 patients was permanent grounding. The time from the attack of the disease to receiving the conclusion of permanent grounding fluctuated from three months to 11 years. CONCLUSION The diagnosis of Meniere's disease of flight aircrew must he cautious. For patients with atypical symptoms of Meniere's disease, the diagnosis should be made in the case of completely ruling out other possible diseases. Once be diagnosed, a patient should normally be flight unqualified. The flying waiver would he recommended only under exceptional circumstances. The criterion of waiver condition need to be further explored in the future.
Adult ; Aerospace Medicine ; methods ; Humans ; Male ; Meniere Disease ; diagnosis ; Middle Aged

Objective To evaluate the hearing function of pilots under physical examination for modification to equipment of high performance aircraft,using pure tone audiometry(PTA) and distortion product otoacoustic emission(DPOAE).Methods Analyzed were all the results of PTA and DPOAE of 75 pilots (150 ears) which accepted physical examination for modification to equipment of high performance aircraft in our department from March 2008 to February 2009.75 cases were divided into two groups according to their flight time.The difference between these two groups was studied.Results According to the Equipments of Physical Constitution for Flying Persons of Air force,PLA,all 75 pilots passed the ENT assessments as being qualified for flying.Of all 150 ears,abnormal DPOAEs were obviously higher than that of abnormal PTA tests.128 ears had normal PTA results.92 ears had normal DPOAE results.36 ears (27.6&) showed abnormal DPOAEs at one or more frequencies,especially at 1,3 and 4 kHz.22 ears had abnormal PTA results.20 ears had noticeable V or U shaped thresholds at 3 kHz and/or 4 kHz.The DPOAE amplitudes showed similar curves.The other two ears showed depressions at all frequencies,in both PTA and DPOAE tests.No statistically significant difference was found between the two groups in DPOAE.But statistical difference was found in DPOAE at 4 kHz compared with other frequencies.No statistically significant differences were found between the two groups in DPOAE amplitudes at 1,2,3 and 4 kHz.but at 6 and 8 kHz.Conclusion The application of DPOAE test helped find pilots who were on the early stage of noise-induced hearing loss.These pilots were the most important objects for us to follow up.