The paper summarizes Professor YANG Jun's thoughts on clinical treatment with acupuncture and moxibustion. Professor YANG Jun puts forward the "refined mode for diagnosis and treatment of diseases with acupuncture and moxibustion", aiming to improve the capacity of diagnosis and treatment in clinical practice. He advocates that the diagnosis and treatment should be guided by the identification of etiologies, syndromes and meridians; in accordance with regulating the shape/form, balancing yin and yang, and harmonizing the mind; and by means of skillful techniques of acupuncture and moxibustion, simplified selection of acupoints and delicate manipulations. Besides, he stresses on the combination of multiple techniques of acupuncture (such as penetrating technique with long needle, stuck needling by lifting and pulling, and micro-acupuncture systems) with moxibustion techniques (moxibustion for resolving stasis and unblocking collaterals, pressing moxibustion, borneol moxibustion, moxibustion with medicinal plaster) in clinical practice, so as to enhance the therapeutic effects.
Moxibustion/methods* ; Acupuncture Therapy/methods* ; Humans ; China ; Acupuncture Points

Background::The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods::From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results::A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A ( n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion::Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Objective:To analyze the advantages of human epididymis protein 4 (HE4) compared with traditional tumor markers in the diagnosis and treatment of lung cancer.Methods:From February 2021 to June 2022, 230 lung cancer patients (138 males, 92 females; age (61.1±12.3) years), 96 benign lung disease patients (62 males, 34 females; age (60.2±14.8) years; including 43 cases of lung benign placeholder and 53 cases of pulmonary infection), and 60 healthy volunteers (40 males, 20 females; age (62.8±11.4) years) from the Second Affiliated Hospital of Soochow University were prospectively collected. Serum HE4, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen (CA)125 were detected by electrochemical analysis. The expression of HE4 in tumor tissues of 55 patients with lung cancer was detected by immunohistochemical method. χ2 test, Mann-Whitney U test, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. The diagnostic efficiencies of HE4 and other tumor markers were evaluated by ROC curve analysis and the difference of AUCs was analyzed by Delong test. Results:The positive expression rate of HE4 in adenocarcinoma tissue was significantly higher than that in non-adenocarcinoma tissue (93.1%(27/29) vs 23.1% (6/26); χ2=28.01, P<0.001). The level of serum HE4 in the lung cancer group (70.70(51.93, 109.05) pmol/L) was significantly higher than that in the pulmonary benign placeholder group (59.80(48.20, 73.50) pmol/L) and the healthy control group (55.25(44.60, 74.25) pmol/L), and that in the pulmonary infection group (97.90(76.62, 155.00) pmol/L) was higher than that in the lung cancer group ( H=46.19, all P<0.008 (Bonferroni correction method)). The levels of serum HE4 were significantly different in age, sex, smoking, disease stage and pathological types in early stage ( z values: from -5.07 to 9.83, all P<0.05). The ROC curve analysis indicated that the optimal cut-off value of serum HE4 for diagnosing lung cancer was 79.22 pmol/L, with the sensitivity and specificity of 41.30%(95/230) and 83.33%(50/60). Compared with other traditional tumor markers, serum HE4 and CA125 showed the higher diagnostic value (AUC CA125 (0.695)>AUC HE4(0.656)>AUC CEA(0.614)>AUC CYFRA21-1(0.599)>AUC ProGRP (0.501)>AUC NSE (0.470)). The combination of HE4 with other traditional tumor markers significantly improved the diagnostic efficacy (AUC=0.750; z=2.75, P=0.006). Conclusions:HE4 is highly expressed in lung adenocarcinoma by immunohistochemistry. Serum HE4 exhibits a great application value in the differential diagnosis between benign and malignant pulmonary nodules, and plays an important role in assessment of patients′ conditions.

The ApoE gene is a genetic risk determinant for sporadic Alzheimer′s disease (AD). The ApoEε4 allele increases the risk of developing AD relative to the common ApoEε3 allele, whereas the ApoEε2 allele decreases the risk of developing the disease. The 3 alleles encode ApoE2, ApoE3, and ApoE4 protein isoforms, respectively. ApoE4 contributes to the pathogenesis of AD by regulating β-amyloid protein, tau protein, transactive response DNA-binding protein-43, neuroinflammation, and cerebral vascular function. The pathways associated with ApoE also offer new opportunities for the treatment of AD. In addition, studies have shown that ApoE4 also plays a toxic role in other neurological disorders. This article described the biological characteristics of ApoE, as well as the impact of ApoE4 on AD and related dementias, aiming to enhance clinical doctors′ understanding of the involvement of ApoE4 in the pathogenesis of AD and related dementia.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

The National Institute on Aging-Alzheimer's Association (NIA-AA) research framework of biological definition of Alzheimer's disease 2018 is introduced to Chinese counterparts to share a common "language" with dementia researchers.The abnormal definitions of Alzheimer's disease (AD),βamyloid deposition (Aβ) and tau,were proposed to be detected by biological methods,and a series of changes before dementia and dementia were proposed to be studied under a unified biological framework.The characteristic biomarkers were defined as AT(N):A is [β amyloid deposition,T is pathological tau protein,and (N) is neurodegeneration.The diversity of the pathological nature of dementia was emphasized,and AD combined with dementia was proposed not to be directly attributable to dementia due to AD.The definition of biomarkers requires more standardization and confirmation of autopsy pathology.