Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment, memory decline and emotional loss, which is more common in middle-aged and elderly people. In recent years, studies have shown that chronic neuroinflammation is an important factor leading to AD development. As the core participant in neuroinflammation, microglia play a dual role in the pathological process of AD: on one hand, through M1 polarization, they exert a pro-inflammatory effect and exacerbate the neurotoxic response; on the other hand, through M2 polarization, they enhance the phagocytic ability of amyloid β-protein and exert a neuroprotective effect. Metabolic reprogramming is the key in determining the polarization of microglia M1/M2 type and exerting neurotoxicity/protection. Therefore, this article reviews the recent advance in role of metabolism reprogramming of microglia in AD, in order to provide new idea and direction for studing AD pathogenesis and treatment in the future.

Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Objective:To establish the TLC identification method and content determination method of ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin in Shangke Huoxue Decoction for quality evaluation.Methods:Ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin were qualitatively identified by TLC method, and the content was determined by HPLC method. Waters Symmetry ShieldTM RP18 column (4.6 mm×250 mm, 5 μm) was set, the mobile phase consisted of acetonitrile-0.15% phosphoric acid water with gradient elution at a flow of 1.0 ml/min, and the column temperature was 30 ℃.The detection wavelength was 320 nm (33-50 min for ferulic acid, 55-70 min for ligustilide), 403 nm (7-31 min for hydroxysafflor yellow A) and 230 nm (7-31 min for paeoniflorin).Results:The TLC spots were clear. The linear relationships of ferulic acid, ligustilide, and hydroxysafflor yellow A were good in the range of 3.05-48.74 μg, 3.50-26.24 μg, 21.34-213.44 μg. The method was stable, repeatable with good recovery rate.Conclusion:The TLC and HPLC method for the simutanous determination of the four effective components in Shangke Huoxue Decoction were established, and the methods are suitable for the quality evaluation of Shangke Huoxue Decoction.

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Objective:To optimize the extraction process of Huoxue-Sanyu effervescent tablets. Methods:The hydroxysafflor yellow A content, paeoniflorin and dry extract yield were used as the evaluation indexes, by using analytic hierarchy process (AHP) method, integrative graded indicators method combined with orthogonal test and back propagation (BP) artificial neural network. To optimize the technics parameters, such as the amount of water, extraction time and frequency.Results:Paeoniflorin and hydroxysafflor yellow A showed good linear relation in the range of 0.079 5-1.590 4 μg and 0.038 5-1.539 2 μg respectively, with the average recovery rates of 98.18% and 96.22%. RSD was 0.77% and 1.31% respectively. The optimum extraction technic was 9 times of water, 3 times of heating reflux extraction, and each extraction last for 1 hour. Conclusions:The optimized combined method of orthogonal experiment and BP artificial neural network is practical with high efficiency. The optimal extraction process is stable and reasonable.

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4
Adaptive Immunity/physiology* ; Adult ; Aged ; Antibodies, Neutralizing/blood* ; COVID-19/immunology* ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood* ; Male ; Middle Aged ; SARS-CoV-2/immunology* ; T-Lymphocytes/physiology* ; Time Factors ; Viral Proteins/immunology*

Objective:To summarize the application of phage therapy in patients with urinary tract complicated pandrug-resistant Klebsiella pneumoniae infection, and analyze its feasibility and effectiveness.Methods:To retrospectively analyze the clinical data of a patient with complicated urinary tract complex pan-resistant Klebsiella pneumoniae treated by phage from August to September, 2019 in Shanghai Public Health Clinical Center. The female patient, 65 years old, was admitted to the hospital on August 6, 2020. The patient repeated with frequent micturition and urgent micturition half a year before admission. These symptoms were not accompanied by back pain, fever, chills, dysuria, gross hematuria. Urinary culture results in outpatient hospital was pan-resistant Klebsiella pneumoniae. After the patient discontinued application of cefoperazone sulbactam, levofloxacin and other drugs, symptoms such as frequent urination could be relieved after treatment, but appeared repeatedly. In August 2019, the center innovatively applied phage therapy to treat this patient with urinary tract pandrug-resistant bacteria infection.Results:For the first time, we applied 117, 135, 178, GD168 phage mixed solution once a day, for 5 days of continuous bladder infusion. At the same time, meropenem and amikacin was intravenous administration to strengthened the anti-infection treatment. Urine culture was negative for two consecutive times after treatment. However, half a month after the end of the bladder infusion, the patient experienced discomfort such as frequent urination. Urine culture: pan-resistant Klebsiella pneumoniae. The second time, we applied a mixture of three phage strains 130, 131, 909, once a day, for 5 days of continuous bladder infusion. And in the afternoon of the third day of treatment, the renal pelvis was retrogradely intubated and perfused with the above three strains of phage mixture. During the second treatment follow-up until March 30, 2020, the patient's urine culture was reviewed once a month. As a result, no pan-resistant Klebsiella pneumoniae was found, and the patient no longer experienced frequent urination and other symptoms of urination. The treatment process was successful and without severe complications and side effects.Conclusions:Phage urinary tract perfusion is an effective method for the treatment of pan-resistant Klebsiella pneumoniae urinary tract infections. The curative effect is accurate and reliable. The patient did not show obvious complications and adverse reactions during treatment. It can be used as an alternative treatment plan for complex pan-resistant Klebsiella pneumoniae infection.

OBJECTIVE: To analyze the clinical phenotype and genetic basis of a consanguineous pedigree affected with hereditary coagulation factor XII (FXII) deficiency. METHODS: Following extraction of genomic DNA, all exons and flanking regions of F12 gene were subjected to PCR amplification and Sanger sequencing. ClustalX-2.1-win and MutationTaster software was used to analyze the conservation and impact of the variants on protein function. RESULTS: DNA sequencing showed that the proband carried a homozygous g.6753-6755delACA deletion (p.252delAsn) in exon 9 of the F12 gene, for which her father, mother and brother were heterozygous carriers. The same deletion was not found in her sister. CONCLUSION The homozygous p.252delAsn deletion probably underlies the hereditary FXII deficiency in this pedigree.