Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Objective To observe the ultrasonic manifestations and outcome of fetuses with absent middle phalanx of the little finger.Methods Data of 36 fetuses with absence of middle segment of the little finger displayed by the first prenatal ultrasound at 16-33 weeks of gestation were retrospectively analyzed.The prenatal ultrasonic manifestations,complicated abnormalities,the chromosomal karyotype results and the outcome of fetuses were recorded.Results Prenatal ultrasound showed 21 fetuses with bilateral absences of middle segment of the little fingers simultaneously with one or more other abnormalities,including 16 fetuses with cardiac malformations,8 with central nervous system malformations,5 with facial malformations,3 with abdominal anomalies and 6 fetuses each complicated with 1 other abnormality.Four of these 21 fetuses received chromosomal karyotype examination,including 2 were found with abnormal chromosomal number(1 of 21-trisomy syndrome and 1 of 18-trisomy syndrome)while the other 2 without chromosomal abnormality.Thereafter,induced labor was performed in 19 cases,while hands DR 3 months after birth displayed ossification centers of middle segment of bilateral little fingers in the rest 2 cases.Among other 15 fetuses prenatal ultrasound showed unilateral(n=2)or bilateral(n=13)absence of middle segment of the little fingers but without other abnormality and underwent chromosomal examination,induced labor was performed in 3 cases with fetal 21-trisomy syndrome,while the other 12 fetuses without abnormal findings were born with no flexion of the little fingers on physical examination,and hands DR 3 months after birth displayed ossification centers of middle segment of bilateral little fingers.Conclusion Displaying of fetal middle segment of the little fingers on prenatal ultrasound was affected by multiple factors,in addition,the ossification might be delayed,and might complicated with other systemic and chromosome abnormalities.Dynamically follow-up with prenatal ultrasound and comprehensively evaluation combined with clinical data was necessary for diagnosing fetal absent middle phalanx of the little finger.

Palliative care not only embodies modern life perspectives, but also encompasses significant traditional Chinese cultural elements.The primary objective of palliative care is to alleviate patient suffering, preserve their dignity, and facilitate a peaceful passing.Traditional Chinese medicine, known for its simplicity, accessibility, affordability, and efficacy in disease prevention and treatment, adopts a holistic approach to address systemic pain through personalized treatment based on symptom differentiation.This approach aims to enhance the quality of life for terminally ill patients.To equip palliative care providers with essential clinical skills in traditional Chinese medicine, the National Center of Gerontology and Beijing Palliative Care Guidance Center collaborated with experts and scholars to develop guidelines focusing on common end-of-life symptoms.Through extensive deliberation, expert evaluation, and revisions, this guidance document was crafted as a valuable resource for palliative care practitioners, traditional Chinese medicine clinicians, and researchers in the field.

Objective:To analyze the metabolic mechanism of papillary thyroid cancer(PTC) in normal and Hashimoto′s thyroiditis(HT) background, and to explore the relationship between HT and PTC.Methods:This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019, consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group), and 30 cases without(NC group), all confirmed pathologically following thyroidectomy. The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to acquire data from the samples. Metabolite differences between the two groups were compared, aiming to identify distinct metabolic mechanisms of PTC under different backgrounds. Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results:The HT group and NC group shared 7 common differentially expressed metabolites, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil, and taurine. Logistic regression model combined with receiver operating characteristic(ROC) analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973, respectively). The common metabolic pathways were taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and glutamine and glutamic acid metabolism. The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis, glycine, serine, and threonine metabolism.Conclusion:The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT. The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine, serine, and threonine.

Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (aHR=2.16, 95%CI:1.20-3.90) and 20-29 age group (aHR=5.48, 95%CI:2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (aHR=1.67, 95%CI:1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95%CI:1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.
Cohort Studies ; DNA, Viral ; Hepatitis B/epidemiology* ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/epidemiology* ; Humans ; Risk Factors ; Young Adult

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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Cachexia/therapy* ; Combined Modality Therapy ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasms/complications* ; Nutritional Support/adverse effects* ; Quality of Life

Objective:To evaluate the correlation between the timed up and go(TUG)test and fall risks in elderly frail patients.Methods:From July to September 2019, elderly frail patients who were treated at the cardiovascular department of our hospital were enrolled.Basic clinical data and fall-related information of patients were collected.Patients were divided into the fall group and the non-fall group.Results on the body mass index(BMI), TUG, 4-meter maximum walking speed(4 m MWS)and Barthel index were compared between the two groups.The correlation between TUG and each indicator was examined.Multivariate Logistic regression analysis was used to analyze the correlation between the TUG and falls in elderly patients.Results:A total of 96 eligible patients were enrolled, including 35 in the fall group and 61 in the non-fall group.The average TUG time was longer in the fall group than in the non-fall group(16.45±6.44 s vs.10.17±2.91 s, t=-6.556, P<0.001). The correlation analysis results showed that the TUG was correlated with falls and 4 m MWS( r=0.582 and 0.875, both P<0.001). Multivariate Logistic regression analysis showed that the TUG( OR=1.201, 95% CI: 1.111-1.470, P=0.004)and 4 m MWS( OR=1.146, 95% CI: 1.063-1.244, P=0.015)were risk factors for falls. Conclusions:The TUG is correlated with fall risks in elderly frail patients and should be recommended as a routine test in clinical practice.

Objective:To investigate the intervention effect of topical shikonin on an imiquimod-induced psoriasis-like mouse model and its effect on expression of CCAAT enhancer binding protein δ (CEBPD) .Methods:Twenty specific pathogen-free BALB/c male mice were randomly and equally divided into model group, shikonin 1 group, shikonin 2 group and blank control group by using simple random sampling. Mice in the model group, shikonin 1 group and shikonin 2 group were topically treated with 50 mg of 5% imiquimod cream every day on the shaved back to establish the psoriasis-like mouse model. After 6-hour treatment, mice in the shikonin 1 group and shikonin 2 group were treated with 0.5 ml of shikonin at concentrations of 0.576 and 5.76 g/L respectively in the modeling area for 8 consecutive days; the blank control group received no treatment. Changes in the skin lesions of these mice were observed by naked eyes every day, and evaluated by using psoriasis area severity index (PASI) ; after 8-day treatment, the mice were sacrificed by cervical dislocation, the dorsal skin tissues were resected, and immunohistochemical study and Western blot analysis were performed to determine the expression of CEBPD in the mouse epidermis. Statistical analysis was carried out with SPSS 16.0 software by using one-way analysis of variance for comparisons of observation indices among different groups, as well as least significant difference- t test for multiple comparisons. Results:On day 8, the mice in the model group presented with obvious erythema, scales, and infiltrative and thickened skin lesions; compared with the model group, the skin lesions were markedly improved in the shikonin 1 group and shikonin 2 group, and the improvement was more obvious in the shikonin 2 group. On day 8, the PASI score significantly differed among the blank control group, model group, shikonin 1 group and shikonin 2 group (0, 11.0±1.22, 8.6±0.55, 5.8±1.30 points, respectively; F=128.21, P<0.01) , and there were significant differences between any two groups (all P < 0.01) . Immunohistochemical study showed a significant difference in the expression of CEBPD ( A value) among the model group, shikonin 1 group, shikonin 2 group and blank control group (0.072±0.026, 0.177±0.036, 0.290±0.062, 0.407±0.051, respectively; F=48.895, P < 0.01) , and there were also significant differences between any two groups (all P < 0.01) . Western blot analysis showed that the CEBPD expression in the mouse epidermis was highest in the blank control group, followed in descending order by the shikonin 2 group, shikonin 1 group and model group, and significantly differed among the above 4 groups ( F=10.237, P<0.05) ; moreover, there were significant differences in the CEBPD expression between the model group and blank control group, as well as between the shikonin 1 group and blank control group (both P<0.05) , while no significant difference was observed between the shikonin 2 group and the blank control group ( P > 0.05) . Conclusion:Topical shikonin could effectively interfere with the development of imiquimod-induced psoriasis-like mouse model; CEBPD expression decreased in the psoriasis-like mouse model, and could be markedly upregulated by topical application of shikonin.

Objective:To investigate the method and effect of acellular dermal matrix (ADM) allograft combined with fat grafting for penile augmentation.Methods:The first phase of enhancing the penile augmentation was using the dual plane approach with acellular dermal matrix, and the second phase was injecting autologous fat into the layer between dartos fascia and buck fascia.Results:23 patients were followed up for 6 months after operation, their penile circumference at flaccid after the operations (11.08±1.67) cm was increased significantly compared to that before the operations (7.87±1.08) cm. All patients were satisfactory with the cosmetic and functional results, and no fat liquefaction, necrosis and other complications happened.Conclusions:Acellular dermal matrix allograft combined with fat injection is an effective and safe way for penile augmentation, which has the characteristics of good shape and few complications.

Objective To explore the association between the different forms of in vivo ghrelin—Acyl ghrelin( AG) ,Des-acyl ghrelin( DAG) and AG/DAG with insulin resistance( IR) in patients with type 2 diabetes mellitus. Methods From June 2017 to November 2017,eighty-three patients with type 2 diabetes hospitalized in (group T2DM) and 40 healthy subjects (group NC) were hospitalized in Jinling Clinical Medicine were selected. Height body mass,blood pressure,blood lipid,glycated hemoglobin ( HbA1c) and fasting blood glucose (FPG),fasting insulin (FINS),and fasting C peptide (F-C-p) were measured,and all subjects were left with fasting serum,and the concentration of AG and DAG were measured by enzyme linked immunosorbent assay (ELISA). The body mass index (BMI),total gastric starvation (T-ghrelin) level,AG/DAG,insulin resistance index ( HOMA-IR) , insulin sensitivity index ( HOMA-IS ) and islet beta cell function ( HOMA- beta ) were calculated. The differences of the above indexes between the two groups were compared, and the relationship between AG,DAG,T-ghrelin,AG/DAG and FPG,HOMA-IR,HOMA-IS and HOMA- beta in T2DM patients were analyzed. Results ( 1) There were no significant difference in SBP、DBP、TC、LDL-C、AG between group NC and group T2DM(P>0. 05). Compared with NC group,the age、TG、BMI、HbA1c、FPG、FINS、HOMA-IR、HOMA-β、AG/DAG were significantly higher in T2DM group ( t=2. 690,-1. 990, 0. 873, 14. 257, 10. 528, Z=2. 885,-3. 483,-2. 284;P<0. 01,P<0. 05) . The HDL-C,F-C-p,HOMA-IS,HOMA-beta,DAG and T-ghrelin in group T2DM were lower than those of NC group( t or Z=0. 477,-3. 812,-3. 395,-4. 4,-2. 916,-2. 834;P<0. 05 or P<0. 01) . ( 2) The correlation analysis showed that there was a positive correlation between AG and FPG in T2DM group (r=0. 252,P<0. 05),DAG and T-ghrelin were negatively correlated with HOMA-IR (r=-0. 394,-0. 384,P<0. 05),and AG/DAG was positively correlated with HOMA-IR (r=0. 394,0. 384,P<0. 05),but is negatively correlated with HOMA-IS (r=-0. 292,P<0. 05). (3) multivariate linear regression analysis showed that FPG in T2DM patients were the influencing factors of AG ( t=2. 865,P<0. 05) ,while FINS and BMI were the influencing factors of DAG( t=-2. 808、-0. 330,P<0. 05) andT-ghrelin( t=-2. 725、-0. 330, P<0. 05) . HOMA-IR and BMI are the influencing factors of AG/DAG ( t=3. 718,3. 069,P<0. 05) . Conclusion The levels of DAG and T-ghrelin in group T2DM were significantly lower than those in the normal population, and was negatively correlated with the insulin resistance index,and the ratio of AG/DAG was closely related to insulin resistance,and the level of AG was mainly affected by fasting blood glucose.