With the continuous intensification of aging， chronic diseases among the elderly have become a widely concerned public health issue. In the terminal stage， they often lose the ability to express their medical care wishes autonomously， leading to a disconnect between medical decision-making and the actual needs of the patients and increasing their physical and psychological suffering. With the rapid aging process in China， the incidence of chronic diseases in the elderly is continuously rising， which has become a serious public health problem. Studies have shown that advance care planning （ACP） has achieved remarkable results in maintaining the dignity of life for terminal chronic disease patients， improving patients’ quality of life， as well as alleviating the physical， mental， and economic burdens on their families. Therefore， the implementation of ACP is crucial for elderly patients with chronic diseases. This paper reviewed the concept of ACP， as well as application effects， challenges and limitations， and corresponding recommendations and countermeasures of ACP in elderly patients with chronic diseases， with a view to providing a solid theoretical and practical basis for the application of ACP in elderly population with chronic diseases in China.

Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.

Objective:To explore the application value of humidifying high-flow nasal cannula oxygen therapy (HHFNC) in children with pediatric intensive care unit (PICU) after weaning.Methods:From January 2018 to October 2021, 42 children with endotracheal intubation admitted to PICU of Tai′an city Central Hospital were prospectively selected and randomly divided into HHFNC group and nasal continuous positive airway pressure (NCPAP) group, with 21 patients in each group. The blood gas analysis [arterial partial pressure of oxygen (PaO 2), partial pressure of carbon dioxide in artery (PaCO 2), PaO 2/oxygen concentration (FiO 2)], blood oxygen saturation (SaO 2), comfort, non-invasive ventilation time, and total hospital stay of the two groups of children 1 hour after using HHFNC and NCPAP were compared, and the rate of reintubation of trachea within 48 hours, gastroesophageal reflux, nasal injury, facial skin indentation, abdominal distension, and pulmonary air leakage were recorded. Results:There was no significant difference between the two groups in terms of blood gas analysis (PaO 2, PaCO 2, PaO 2/FiO 2), SaO 2, pulmonary air leakage, non-invasive ventilation time, hospital stay, and reintubation rate within 48 h after weaning (all P>0.05). Compared with NCPAP group, HHFNC group had higher comfort, lower incidence of facial skin indentation, gastroesophageal reflux, nasal injury and abdominal distension, and the difference was statistically significant (all P<0.05). Conclusions:HHFNC and NCPAP can both be used as the transitional respiratory support mode after weaning, and the clinical treatment effect are similar. The HHFNC group has higher comfort, which is more conducive to improving the tolerance of children, reducing adverse reactions, and has higher safety.

A 24-year-old female patient presented with recurrent itchy annular erythema and scales on the trunk and extremities for 9 years. Histopathological study revealed hyperkeratosis with focal parakeratosis, neutrophil aggregation in the stratum corneum, blisters below the stratum corneum, and perivascular infiltration with lymphocytes, a small number of eosinophils and neutrophils in the superficial and middle dermis. Direct immunofluorescence assay showed negative staining for IgG, IgM, IgA and C3. Whole-exome sequencing of the SPINK5 gene showed a missense mutation c.2423C>T (p.T808I) in exon 25, and a splicing site mutation c.2965-1G>A in exon 31. The compound heterozygosity for the two mutations may be the cause of Netherton syndrome in the patient. Based on the clinical manifestations and genetic testing results, the patient was diagnosed with Netherton syndrome.

Objective: Study on the improvement of quality standard for Zicao ointment. Methods: The content of shikonin and β,β’-dimethylacrylshikonin was determined by high performance liquid chromatogram (HPLC). The column was Inertsil ODS-3 C18 column (4.6 mm×250 mm, 5 μm). The mobile phase comprising of acetonitrile-0.05% formic acid solution (70:30). The flow rate was 1.0 ml/min, the detection wavelength was 275 nm, and the column temperature was 25 ℃. Results: The linear range of shikonin and β,β’-dimethylacrylshikonin were 0.04-0.81 μg (r=0.999 5) and 0.41-10.36 μg (r=0.999 2). The average recovery were 103.32% and 101.80%, the RSD were 1.96% and 2.11%. Conclusions The method is simple, accurate and sensitive to control the quality of Zicao ointment.

BACKGROUND: miRNA plays a critical regulatory role in the development and plasticity of spinal cord, and pathological changes after spinal cord injury. OBJECTIVE: To study the effect of miR-136-5p on the A20 expression in mouse astrocytes stimulated by interleukin-17 (IL-17). METHODS: C57BL/6 mouse astrocytes were cultured in vitro, identified by immunofluorescence staining, and then stimulated by 100 μg/L IL-17 for 0, 3, 6, 12 and 24 hours, respectively. The relative mRNA expression levels of IL-6 and tumor necrosis factor-α were detected by RT-PCR to determine the optimal stimulation time of IL-17. The mouse astrocytes were respectively stimulated by 10, 20, 50, 100 and 200 μg/L IL-7 for 6 hours, and similarly, the relative mRNA expression levels of IL-6 and tumor necrosis factor-α were detected to determine the optimal concentration of IL-17. At 6 hours after IL-17 (50 μg/L) stimulation, the mRNA expression levels of miR-136-5p and A20 in mouse astrocytes were detected by RT- PCR, and the protein expression level of A20 was detected by western blot assay. In addition, the lentiviral expression vector (miR-136-5p-inhibition) was constructed and transfected into the mouse astrocytes that were also stimulated by IL-7 to detect the expression levels of miR-136-5p, A20 mRNA and A20 protein. RESULTS AND CONCLUSION: Compared with the blank control group, the expression level of miR-136-5p in the miR-136-5p-inhibition group was significantly decreased after 6-hour IL-17 stimulation (P < 0.05). The expression levels of A20 mRNA and protein in each group were significantly decreased after 6-hour IL-17 (50 μg/L) stimulation (P < 0.05). The expression levels of A20 mRNA and protein in the miR-136-5p-inhibition group were significantly higher than those in the blank control group (P < 0.05), while there were no significant differences in the expression level of A20 protein between blank control and negative groups (P > 0.05). To conclude, miR-136-5p makes certain effect on the expression of A20 protein in astrocytes after IL-17 stimulation.

Objective To discuss the correlation of serum TNFR level with renal function injury in patients with type 2 diabetes mellitus (T2DM)and normal albumin excretion.Methods 90 T2DMpatients with normal albu-min excretion(24h urine albumin excretion rate <20μg/min)were divided into three groups according to the esti-mated glomerular filtration rate level:eGFR >90mL · min -1 · (1.72m2 )-1 ,eGFR 60 -90mL · min -1 · (1.72m2 )-1 and eGFR <60mL·min -1 ·(1.72m2 )-1 ,30 cases in each group.The serum TNFRs level and related clinical data were measured and analyzed statistically.Results The levels of serum TNFR1,TNFR2 were negatively correlated with eGFR(r =-0.428,-0.335,all P <0.05),and positively correlated with Scr(r =0.476,0.225,all P <0.05)in patients with T2DM and normal albumin excretion.The course of disease and the levels of BUN,Scr, CysC,α1 -MG,β2 -MG were increased as the degree of renal function injury.All these index had statistically signifi-cant differences in three groups(F =3.758,5.851,71.738,25.751,7.530,13.735,all P <0.05).Logistic regres-sion analysis showed that the levels of serum TNFR1,TNFR2 were independent risk factors for renal impairment in patients with T2DMand normal albumin excretion(OR =2.009,1.143,all P <0.05).Conclusion TNFRs may be involved in the development and progression of renal impairment,and may become a new conventional indicator for DN because of reflecting the degree of renal function injury in some extent in T2DMpatients with normal albumin excretion.

Objective To investigate the effects of long-term consumption of Fallopia multiflora on mouse hematopoietic system.Methods Forty 10-month old female C57BL/6J mice were equally divided into two groups at random, the control group fed with normal food , and the experimental group , given food with added Fallopia multiflora. After 10 month, the mice were sacrificed, and the peripheral blood, spleen, thymus and bone marrow cells were examined by flow cytometry.Results In the mice fed with Fallopia multiflora, the percentage of B cells in the spleen and CD 4 +cells in the thymus were increased , and CD8 + cells in the thymus and bone marrow hematopoietic stem cells were decreased , among the bone marrow cells , G0 cells were increased , but G1 and G2/S/M cells decreased .Conclusions Long-term proper consumption of Fallopia multiflora can delay the ageing of the hematopoietic system , and sustain its stability.

Objective To evaluated the effectiveness and safety ofLianhua Jizhi Tablets for acute trachitis and bronchitis with syndrome of phlegm-heat obstructing.Methods A randomized double-blind, placebo-controlled and multi-center clinical trial design was selected. Totally 240 cases were randomly divided into experimental group and control group, 120 cases in each group, of which 237 cases were included in the analysis of FAS. Experimental group was givenLianhua Jizhi Tablets, while control group was given placebo, 12 tablets/day, 7 days for a course. Curative effect of acute trachitis and bronchitis, TCM syndrome and disappearance of cough, cough and sputum symptom scores and area under the curve (AUC) were observed. The safety was evaluated. Results The cure rates of disease in experimental group and control group were 66.67% (78/117) and 29.17% (35/120), respectively;cure rates of TCM syndrome in experimental group and the control group were 68.38% (80/117) and 27.50% (33/120), respectively;there was statistically significant difference in area under the curve of cough and sputum symptom score between the two groups (P<0.01). Disappearance rates (cure) of daytime cough in experimental group and control group were 52.99% (62/117) and 13.33% (16/120), respectively;disappearance rates (cure) of nocturnal cough in experimental group and control group were 76.52% (88/115) and 31.90% (37/116), respectively;there were no side effects in experimental group.ConclusionLianhua Jizhi Tablets can significantly relieve clinic symptoms in the treatment of acute trachitis and bronchitis, and have good clinical efficacy and safety.