Objective Study on the diagnosis value of expression of serum macrophage inhibitory factor 1 (MIC-1) combined with alpha-fetoprotein isoforms 3 (AFP-L3) in primary liver cancer detected by enzyme linked immunosorbent assay (ELISA).Methods MIC-1 and AFP-L3 concentrations were detected by ELISA from selected 116 patients of primary liver cancer.Results were compared both in combined and sigle detection.Results In primary liver cancer group AFP-L3 concentration [(127.12±51.43) ngmml] was significantly higher than that in normal control group [(27.11±7.26) ng/ml,P ＜ 0.001].With AFP-L3 ＞ 38.0 ng/ml as the critical value,the sensitivity was 85.34 ％ (99/116),specificity was 88.33 ％ (53/60) and the diagnostic accuracy was 86.36 ％ (152/176).In primary liver cancer group MIC-1 concentration [(3140.43±1138.23) pg/ml]was significantly higher than that in normal the control group [(701.88±302.34) pg/ml,P ＜ 0.001],the sensitivity was 91.38 ％ (106/116),specificity was 85.00 ％ (51/60),the diagnostic accuracy was 89.20 ％(157/176).The two combined detection sensitivity was 83.62 ％ (97/116),specificity was 91.67 ％ (55/60),diagnostic accuracy was 86.36 ％ (152/176).Conclusion MIC-1 combined with AFP-L3 concentration detection can improve the specificity of the diagnosis of primary liver cancer,which has certain clinical value.

Objective:To compare the choriocapillaris flow density and choroidal vessel volume (CVV) of acute and chronic central serous chorioretinopathy (CSC).Methods:A cross-sectional observational clinical study. A total of 64 eyes of 64 patients (CSC group) diagnosed with CSC at Department of Ophthalmology of West China Hospital of Sichuan University from May 2019 to October 2020, and a total of 64 eyes of 64 age and gender matched healthy volunteers (control group) during the same period were included in this study. In the CSC group, there were 34 patients with acute CSC (acute CSC group) and 30 patients with chronic CSC (chronic CSC group). There was no significant difference in age ( t=-0.041) and sex composition ratio ( χ2=0.191) between CSC group and control group ( P>0.05). There were statistically significant differences in age ( t=-1.872) and sex composition ratio ( χ2=8.778) between acute CSC group and chronic CSC group( P<0.05). Swept source optical coherence tomography angiography (SS-OCTA) was performed using VG200D. The scanning mode was 512×512 and scannig range was 12 mm × 12 mm. The choriocapillaris flow density of the 3 mm, 6 mm, 12 mm circular area and 1-3 mm ring, 3-6 mm ring, and 6-12 mm ring, and the CVV of the of the 3 mm, 6 mm, 12 mm circular area was automatically generated by the built-in software (v1.28.6). The age, choriocapillaris flow density and CVV were compared between two groups using independent sample t test. Results:Compared with the control group, the choriocapillaris flow density decreased in the CSC group, and there were statistically significant differences in the 3 mm, 6 mm circular area ( t=-7.210, -4.040; P<0.001). There were statistically significant differences between CSC group and control group in the 3 mm, 6 mm, 12 mm circular area ( t=1.460, 12.270, 11.250; P<0.05). Compared with the acute CSC group, the choriocapillaris flow density decreased in the chronic CSC group, and there were statistically significant differences ( P<0.05) in the 3 mm, 6 mm circular area ( t=3.230, 2.330), the total and four quadrants of 1-3 mm ring ( t=2.780, 2.060, 2.140, 2.620, 3.770), the superior quadrants of the 3-6 mm ring ( t=2.550), and the superior and temporal of 6-12 mm ring ( t=3.070, 2.610). There was no significant difference of CVV in the 3 mm, 6 mm and 12 mm circular area between the acute CSC group and the chronic CSC group ( t=0.250, 0.070, -0.110; P>0.05). Conclusion:Compared with acute CSC, chronic CSC exhibits significant decreased choriocapillaris flow density and no change in CVV.

Objective To observe the changes and clinical significance of procalcitonin(PCT) level in children with bacterial pneumonia.Methods The levels of PCT,hs-CRP and WBC were detected in 31 pneumonia children pre and post antibiotic treatment,and the changes were observed.Results The PCT levels of the 31 patients were all increased before treatment.After cured,PCT level of 28 cases returned to normal.But in the 28 normal cases,WBC level increased in 10 cases(35.7％),and hs-CRP level elevated in 4 cases(14.3％).In the other 3 cases,the PCT levels decreased from 5.69ng/mL,1.25ng/mL and 0.83ng/mL at admission to 0.51ng/mL,0.55ng/mL and 0.52ng/mL,respectively.And in these 3 cases,there was one case with the levels of WBC and hs-CRP respectively ascended,in which WBC level descended from 13.1 × 109/L to 12.1 × 109/L and hs-CRP level reduced from 20.92mg/L to 7.38mg/L.Conclusion The sensitivity of the index PCT is the highest at the accurate time phase of bacterial pneumonia,which can guide the reasonable use of antibiotics.

Objective:To investigate the diagnostic values of human epididymis protein 4 (HE4), endothelial cell specific molecule-1 (ESM-1) and epidermal growth factor receptor (EGFR) for lung cancer.Methods:The clinical data of 90 patients with lung cancer and 50 patients with benign lung diseases diagnosed by the pathological examination in Tangshan People's Hospital from December 2019 to January 2021 were retrospectively analyzed, and 40 healthy physical examiners in the same period were selected as the controls. The serum HE4 levels were detected by electrochemiluminescence method. The serum ESM-1 and EGFR levels were tested by enzyme-linked immunosorbent assay. The differences in serum HE4, ESM-1 and EGFR levels between the three groups were compared; logistic regression analysis was used to screen out the effective indicators for the diagnosis of lung cancer and to construct a prediction model for the diagnosis of lung cancer. Using pathological diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of indicators for lung cancer was evaluated.Results:The levels of serum HE4 in lung cancer group, benign lung diseases group and healthy control group were 119.55 pmol/L (82.06 pmol/L, 189.00 pmol/L), 58.84 pmol/L (45.62 pmol/L, 69.41 pmol/L) and 42.67 pmol/L (37.09 pmol/L, 51.84 pmol/L), the levels of ESM-1 were 33.00 ng/ml (25.85 ng/ml, 47.40 ng/ml), 20.14 ng/ml (11.93 ng/ml, 28.90 ng/ml) and 15.39 ng/ml (11.84 ng/ml, 20.19 ng/ml), and the levels of EGFR were 46.60 pg/ml (37.45 pg/ml, 58.98 pg/ml), 32.77 pg/ml (26.27 pg/ml, 40.86 pg/ml) and 30.43 pg/ml (27.54 pg/ml, 35.75 pg/ml), and the differences in each indicator among the three groups were statistically significant (all P < 0.001). The levels of serum HE4, ESM-1 and EGFR in lung cancer group were higher than those in benign lung diseases group and healthy control group. In patients with lung cancer, logistic regression analysis was performed with HE4 (X 1), ESM-1 (X 2) and EGFR (X 3) as the independent variables and pathological diagnosis as the dependent variable, and a lung cancer prediction regression model was established: P = 0.171X 1+0.351X 2+0.184X 3-24.660. The accuracy of this model in predicting lung cancer could reach 98.5%, and serum HE4, ESM-1 and EGFR were risk factors for the occurrence of lung cancer (all P < 0.05). The area under ROC curve from high to low was HE4 (0.960), ESM-1 (0.942) and EGFR (0.859). The diagnostic sensitivity of serum HE4 63.67 pmol/L for lung cancer was 86.7%, and the specificity was 97.5%. Both serum HE4 ( r = 0.304, P = 0.004) and ESM-1 ( r = 0.416, P < 0.001) were correlated with EGFR. Conclusions:Serum HE4, ESM-1 and EGFR can be used as effective indicators for the diagnosis of lung cancer, and the prediction model established based on the three serum tumor markers is of good value for the diagnosis and prediction of lung cancer.

Objective:To investigate the effect of Stigma Maydis Palysaccharide(SMPS)on ATP synthesis in kidney mitochondria of D-galactose-induced aging mice, and to clarify its possible mechanism.Methods:The aging mouse model was established by subcutaneous injection of D-galactose solution in the back of the neck.The 48 SPF male mice were randomly divided into normal control group(control group), D-galactose model group(D-Gal group), SMPS low-dose group and SMPS high-dose group(n=12 for each). The control group was subcutaneously injected with 150 mg/kg normal saline on the back of the neck every day, while the other three groups were subcutaneously injected with 150 mg/kg of D-gal solution on the back of the neck every day.SMPS-L and-H dose groups were given 30 mg/kg and 60 mg/kg of SMPS solution by gavage at the same day of D-Gal injection.The control group and D-GAL group were given the same volume of normal saline daily by gavage for 42 days.Blood samples were collected from the eyeball under general anesthesia after 42 days of intervention for the detection of serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px)and MDA.After harvesting the kidney tissue, various tests were used to detect ATP content, the mRNA expression levels and protein expression levels in kidney.Luciferase assay was used to detect ATP content in renal tissue.Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of succinate dehydrogenase(SDH)of complex Ⅱ, cytochrome C reductase(Cycs)of complex Ⅲ, complex Ⅳ(COXⅣ)and ATP5b in ATP synthase in mitochondrial oxidative respiratory chain.Western blot was used to detect the expression levels of mitochondrial fusion protein 2(MFN2), dynamin-related protein1(DRP1)and mitochondrial autophagy related protein P62 in renal tissues of each group.Results:Compared with control group, the activities of serum of SOD(116.53±10.01)U/mg and GSH-Px(127.58±8.74)μmol/L were significantly decreased in D-GAL group(both P< 0.01), and serum MDA content(15.42±0.91)μmol/L increased significantly in D-GAL group( P<0.01). Compared with D-GAL group, the activities of SOD(152.80±9.29)U/mg and GSH-Px(274.07±10.73)μmol/L were significantly increased in SMPS intervention group( P< 0.01), while the MDA content(8.10±0.66)μmol/L decreased significantly in SMPS intervention group( P< 0.01). Compared with control group, the content of ATP(178±4)10 -4 μmol in D-gal group was significantly decreased( P<0.01), the mRNA expression levels of SDH, Cycs and COXⅣ were not significantly changed in D-gal group, and the mRNA expression level of ATP5b(0.67±0.01)was down-regulated in D-gal group( P<0.01), the expression of MFN2 protein(0.29±0.02)was significantly decreased in D-gal group( P<0.01), and the expression of DRP1 and P62 protein(0.31±0.02 and 0.21±0.01)was significantly increased in D-gal group(both P<0.01). Compared with the D-gal group, the ATP content(193±1)10 -4 μmol in the kidney tissue of the mice was significantly increased in SMPS intervention group( P< 0.01), and the ATP5b mRNA expression and MFN2 protein expression(0.87±0.05 and 0.71±0.08)were significantly increased in SMPS intervention group(both P< 0.01), DRP1 and P62 protein expressions(0.20±0.01 and 0.10±0.01)were significantly down-regulated in in SMPS intervention group(both P< 0.01). Conclusions:SMPS can improve the mitochondrial dynamic homeostasis disorder in aging mice by increasing the activity of antioxidant enzymes, up-regulating the expression of ATP5b mRNA and MFN2 protein, down-regulating the expression of DRP1 and P62 protein, and promoting the generation of mitochondrial ATP in D-gal-induced aging mice kidney tissue.

Objective:To investigate the effect and mechanism of non-selective histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) on neuropathic pain and pain-induced memory impairment in mice.Methods:Forty clean grade male C57BL/6J mice were were divided into 4 groups by random number table method ( n=10 in each group): sham + saline, sham + NaB, chronic constriction injury (CCI)+ saline and CCI + NaB.The mouse CCI model was established by sciatic nerve ligation. Non-selective HDAC inhibitors NaB(300 mg/kg) was intraperitoneally injected into the mice in Sham+ NaB group and CCI+ NaB group once a day 15-28 days after modeling, while the mice in Sham+ saline group and CCI+ saline group were intraperitoneally injected with the same volume of saline. On the 14th and 28th day after operation, the athletic ability was measured by open field test (OFT), the pain behavior was measured by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), and the memory function was measured by Y-maze. After the behavioral experiment, hippocampus and spinal dorsal horn tissues were taken for the activity of HDAC measurement, and hippocampus tissues were taken for the expression levels of BDNF and PSD95 measurement. SPSS 25.0 software was used for statistical analysis. The data were compared by repeated measurement ANOVA and one-way ANOVA. Results:After treatment with NaB, the interaction effects of the accuracy of spontaneous alternation of PWT, PWL and Y maze in mice were significant( F=21.07, 6.98, 7.79, all P<0.05). Compared with the Sham + saline group, the PWT((0.83±0.30)g, (0.25±0.22)g, (0.24±0.11)g; both P<0.05), the PWL((14.97±4.02)s, (5.99±1.51)s, (6.87±0.90)s; both P<0.05) and the spontaneous alternation in Y maze(71.57±2.80)%, (56.96±0.60)%, (62.86±4.94)%; both P<0.05) in CCI+ Saline group and CCI+ NaB group were lower. After treatment with NaB, compared with CCI + saline group, PWT((0.22±0.13)g, (0.62±0.23)g; P<0.05), PWL((5.62±2.00)s, (8.82±2.13)s; P<0.05)and the accuracy of spontaneous alternation of Y maze were significantly higher ((56.54±7.50)%, (66.35±8.20)%; P<0.05), the HDAC activity in hippocampus((173.40±7.38)%, (122.70±8.40)%; P<0.05)and in spinal cord ((153.40±10.58)%, (111.40±11.40)%; P<0.05)were significantly lower, and the expression of BDNF((0.65±0.06), (0.87±0.43); P<0.05)and PSD95((0.70±0.40), (0.87±0.04); P<0.05)were significantly higher in CCI + NaB group. Conclusion:NaB can improve neuropathic pain and pain-induced memory impairment.The mechanism may be related to the inhibition of HDAC activity and the up-regulation of BDNF and PSD95 expression in hippocampus.

Objective　To investigate the role of the p75 neurotrophic receptor (p75 NTR) in the cognitive impairment induced by laparotomy surgery of aged mice,and to explore the possible mechanism.Methods　Thirty eighteen-month-old male mice were equally randomized into three groups (n=10):control group,surgery group,surgery+TAT group.Open field test was performed 5 days after the surgery to record the exploration distance and the time in the center.Fear-conditioned training was performed 6 days after the surgery,and fear-conditioned test was performed 7 days after the surgery to record the freezing time.The hippocampus was harvested immediately after the behavioral test.Western blot was applied to detect the levels of p75NTR,BDNF,PSD95,TrkB and pCREB in the hippocampus,immunofluorescence was applied to detect the number of caspase-3 positive cells in the hippocampus,and Golgi staining was applied to observe the changes of dendritic spines in hippocampal CA-1 region.Results　In the open field test,the total distance and the time in the center had no significant difference among the three groups (P>0.05).In the fear conditioning test,compared with control group,the percentage of the contextual conditional freezing time decreased significantly in surgery group (P<0.05),and the expressions of BDNF，PSD95，TrkB and pCREB and the number of dendritic spines in CA-1 were significantly decreased (P<0.05),the expression of p75NTR and the number of caspase-3 positive cells were increased significantly in the surgery group (P<0.05).Compared with the surgery group,the percentage of the contextual conditional freezing time increased significantly in surgery+TAT group,and the expressions of BDNF,PSD95,TrkB,and pCREB and the number of dendritic spines in CA-1 were significantly increased,the number of caspase-3 positive cells were decreased significantly in the surgery+TAT group (P<0.05).Conclusion　Hippocampal p75 NTR plays a key role in the pathophysiology of POCD.

Allergic rhinitis is a common allergic disease in children.Its pathogenesis is complex and it is difficult to achieve radi-cal cure or effective and stable long-term treatment goals.Chinese medicine has obvious advantages in preventing and treating allergic rhinitis in children due to its wide range of targets,long-lasting effects and few adverse reactions.This paper proposes that the onset of allergic rhinitis is mostly caused by the dysfunction of the lung,spleen and kidney,the external wind triggering the latent wind,and the combination of the two winds.A staged prevention and treatment strategy of Chinese medicine should be adopted,which includes dispersing external wind,suppressing latent wind,and promoting lung-qi and clearing nasal orifice during the attack period to treat its symptoms,and preventing external wind,calming down latent wind,and regulating and tonifying the lung,spleen,and kidney during the remission period to treat its root cause;meanwhile,attention should be paid to avoiding the adverse effects of congenital endowment factors and the induction of acquired environmental factors,strengthening the body's health to protect against the evil wind,preventing the transformation of existing diseases and the recurrence of allergic rhinitis in children at all stages.

Antibody-drug conjugates (ADCs) are conjugated by a linker between an antibody drug targeting a specific antigen and a payload, such as a small cytotoxic drug. ADCs combine the potent killing effect of traditional small cytotoxic drugs with the tumor targeting property of antibody drugs. As of February 2022, the U.S. Food and Drug Administration (FDA) had approved 12 ADC antitumor agents. Based on the analysis of clinical pharmacology review reports of approved ADC drugs combined with relevant guidelines, it is found that in the development of ADC, in addition to the general research in clinical pharmacology, there are special considerations in dose selection and dose modification for special population due to the special anti-tumor mechanism of ADC. It is hoped that this paper will be enlightening to domestic researchers when developing ADC.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.