The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in children with hepatolenticular degeneration (Wilson disease, WD) based on factor analysis and cluster analysis. Methods: From November 2018 to November 2023, general information (gender, age of admission, age of onset, course of disease, clinical staging, Western medicine clinical symptoms, and family history) and TCM four-examination informations (symptoms and signs) were retrospectively collected from 757 cases of children with WD at the First Affiliated Hospital of Anhui University of Chinese Medicine, and factor analysis and cluster analysis were used to investigate TCM syndromes in children with WD. Results: A total of 757 children with WD were included, of which 483 were male and 274 were female; the median age at admission was 12.58 years, the median age at onset was 8.33 years, and the median course of disease was 24.37 months; clinical typing result indicated 506 cases of hepatic type, 133 cases of brain type, 99 cases of mixed-type, and 19 cases of other type; 36.46% of the children had no clinical symptoms (elevated aminotransferases or abnormalities in copper biochemistry); a total of 177 cases had a definite family history, and 10 cases had a suspected family history. Forty-three TCM four-examination information were obtained, with the top 10 in descending order being feeling listless and weak, brown urine, slow action, inappetence, dim complexion, slurred speech, angular salivation, body weight loss, hand and foot tremors, and abdominal fullness. In children with WD, the syndrome element of disease location was primarily characterized by the liver, involving the spleen and kidney, and the syndrome elements of disease nature were characterized by dampness, heat, and yin deficiency. Based on factor analysis and cluster analysis, five TCM syndromes were derived, which were, in order, syndrome of dampness-heat accumulation (265 cases, 35.01%), syndrome of yin deficiency of the liver and kidney (202 cases, 26.68%), syndrome of liver hyperactivity with spleen deficiency (185 cases, 24.44%), syndrome of qi and blood deficiency (79 cases, 10.44%), and syndrome of yang deficiency of the spleen and kidney (26 cases, 3.43%). Conclusion The TCM syndromes of children with WD were primarily syndromes of dampness-heat accumulation, yin deficiency of the liver and kidney, and liver hyperactivity with spleen deficiency. The liver was the main disease location, and the disease nature was characterized by deficiency in origin and excess in superficiality, excess and deficiency mixed. These findings suggest that treating children with WD should be based on the liver while also considering the spleen and kidney.

Guided by the theory of "fire and original qi are restricted"， it is believed that original qi depletion is the root of the cutaneous immune-related adverse events （cirAEs） related to immune checkpoint inhibitors （ICIs）， and the yin fire exuberance is the branch. Among them， original qi depletion is the internal foundation of the disease， while the drug toxicity of ICIs harming original qi is the initiating factor， and exuberant yin fire is the key pathogenesis. In clinical practice， the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction （补中益气汤） can be used to activate transportation of middle jiao （焦） and promote ascent and dispersion of clear yang， thereby restoring the balance of qi and fire， and medicinals such as Huangqin （Radix Scutellariae）， Huanglian （Rhizoma Coptidis） and Huangbai （Cortex Phellodendri Chinensis） can be supplementetd to clear and drain yin fire. At the same time， considering the accompanying symptoms such as dampness-stasis and fluids depletion， the methods of removing dampness and dispelling stasis， supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

AIM: To evaluate the efficacy and safety of interventional therapy combined with tumor drug injection under bronchoscope for central non-small cell lung cancer (NSCLC). METHODS: Sixty-four patients who met the test admission criteria were randomly assigned to the experimental group and the control group according to the ratio of 1:1, and were given bronchoscopic interventional therapy combined with local drug injection of recombinant human endostatin combined with platinum-containing dual-drug chemotherapy and platinum-containing dual-drug alone, respectively. The curative efficiency and safety of the two groups were compared. RESULTS: Compared with the control group, the KPS score, dyspnea grading were significantly improved (P<0.05). The effective rate of the test group was 78.12%, which was higher than 37.5% in the control group, the difference between the two groups was significant (P<0.05). Moreover, there was also a significant difference in the 1-year survival rate between the experimental group and the control group (P<0.05). CONCLUSION: The treatment of central NSCLC by interventional therapy combined with tumor drug injection through fiberoptic bronchoscope has obvious clinical efficacy, which can effectively alleviate the clinical symptoms and improve the quality of life of patients. There is no significant difference in adverse reactions between the two groups, and is worthy of popularization and application.

Objective:The clinical data of prenatal stillbirth were analyzed in order to increase the understand-ing of the causes of stillbirth.Methods:Prenatal stillbirth cases that terminated pregnancy in Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2018 to December 2022 were col-lected,and the distribution characteristics of clinical data and the stillbirth causes were analyzed.The causes of death were classified according to the standards developed by the Stillbirth Collaborative Research Network(SCRN)in the United States,and they were divided into clear cause-of-death group and unknown cause-of-death group.The different characteristics of the two groups were compared and analyzed.Results:There were 210 ca-ses of prenatal stillbirth during the study period,and 104 cases met the inclusion criteria.Among them,33 cases(31.7%)had autopsy results,39 cases(37.5%)had genetic results,and 75 cases(72.1%)had placental pathol-ogy.According to the classification of SCRN standard,55 cases(52.9%)were probably related to the cause of death,33 cases(31.7%)were classified as possible,13 cases(12.5%)were probably unrelated,and 3 cases(2.9%)could not be attributed to the cause of death,that is,84.6%(88 cases)in the clear cause of death group and 15.4%(16 cases)in the unknown cause of death group.The rate of placental pathological examination in the clear cause of death group was significantly higher than that in the unknown cause of death group(78.4%).In the classification of causes of death,placental pathological changes accounted for the largest proportion,account-ing for 26.9%(28 cases),followed by pregnancy complications accounting for 25.0%(26 cases),and 15.4%of the cases were still unexplained.Conclusions:Placental pathology is of great significance for clarifying the cause of stillbirth.It is feasible to use SCRN to classify the etiology of stillbirth.Pathological placental conditions account for a relatively high proportion in the classification of stillbirth causes.It is recommended that each case of stillbirth placenta should undergo pathological examination.

Objective To observe the clinical efficacy and safety of spironolactone combined with sacubitril/valsartan in the treatment of patients with hypertensive nephropathy.Methods The patients with hypertensive nephropathy were randomly divided into control group and treatment group.The control group was treated with sacubitril/valsartan(100-200 mg·d-1 in the morning),and treatment group was combined with low-dose spironolactone treatment(20 mg·d-1 in the morning)on the basis of control group.Both groups were treated continuously for 12 weeks.The clinical efficacy was compared;the blood pressure,urinary microalbumin(mAlb),urinary β2 microglobulin(β2-MG)and serum cystatin C(Cys-C),transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF)and angiotensin Ⅱ(Ang Ⅱ)and adverse drug reactions were observed before and after treatment.Results There were 87 cases in treatment group and 86 cases in control group were included respectively.After treatment,the total effective rates in treatment group and control group were 95.40％(83 cases/87 cases)and 82.56％(71 cases/86 cases),with significant difference(P＜0.05).After treatment,the systolic blood pressure values in treatment group and control group were(124.65±9.65)and(130.27±8.93)mmHg,the diastolic blood pressure values were(75.08±7.14)and(80.45±7.35)mmHg,urinary mAlb levels were(42.58±5.65)and(51.28±6.64)mg·L-1,urinary β2-MG levels were(0.46±0.17)and(0.75±0.25)mg·L-1,24 h urinary protein quantitation levels were(138.49±46.64)and(216.48±65.27)mg,serum Cys-C levels were(0.63±0.26)and(0.85±0.24)mg·L-1,TGF-β1 levels were(98.67±21.43)and(112.46±26.72)pg·mL-1,CTGF levels were(1 206.54±236.56)and(1 340.51±248.25)pg·mL-1,Ang Ⅱ levels were(101.55±17.62)and(115.65±20.08)pg·mL-1,all with significant difference(all P＜0.05).The incidence of adverse drug reactions in treatment group and control group were 6.90％(6 cases/87 cases)and 2.33％(2 cases/86 cases),with no significant difference(P＞0.05).Conclusion Compared with sacubitril/valsartan alone,spironolactone combined with sacubitril/valsartan can better reduce blood pressure,improve renal function and delay progression of renal fibrosis in the treatment of hypertensive nephropathy,and has definite efficacy,with good safety.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.