This paper summarizes Professor WANG Xiuxia's clinical experience in treating hyperprolactinemia using the liver soothing therapy. Professor WANG identifies liver qi stagnation and rebellious chong qi （冲气） as the core pathomechanisms of hyperprolactinemia. Furthermore， liver qi stagnation may transform into fire or lead to pathological changes such as spleen deficiency with phlegm obstruction or kidney deficiency with essence depletion. The treatment strategy centers on soothing the liver， with a modified version of Qinggan Jieyu Decoction （清肝解郁汤） as the base formula. Depending on different syndrome patterns such as liver stagnation transforming into fire， liver stagnation with spleen deficiency， or liver stagnation with kidney deficiency， heat clearing， spleen strengthening， or kidney tonifying herbs are added accordingly. In addition， three paired herb combinations are commonly used for symptom specific treatment， Danggui （Angelica sinensis） with Chuanxiong （Ligusticum chuanxiong）， Zelan （Lycopus lucidus） with Yimucao （Leonurus japonicus） ， and Jiegeng （Platycodon grandiflorus） with Zisu （Perilla frutescens）.

Objective To discuss the correlation of serum visceraladiposetissue-derived serineproteinase inhibitor(vaspin)and atrial fibrosis biochemical markers in atrial fibrillation(AF)patients.Methods The subjects were selected from inpatients in Shanghai Putuo District People's Hospital during January 2021 to October 2022.Enzyme linked immunosorbent assay(ELISA)was used to determine the levels of serum vaspin,C-terminal propeptide of prollagen type Ⅰ(PⅠCP),matrix metalloproteinase-1(MMP-1),N-terminal type Ⅲ collagen peptide(PⅢNP),tissue matrix metalloproteinase inhibitory factor-1(TIMP-1)of paroxysmal atrial fibrillation(PAF)group,persistent atrial fibrillation(PeAF)group,and control group.The correlation between serum vaspin and the above serum biochemical markers was analyzed.Results ①Levels of serum vaspin(9.51±1.47)ng/ml,PⅠCP(704.83±120.45)ng/ml,MMP-1(5.92±0.73)ng/ml,PⅢNP(63.34±12.24)ng/ml,and TIMP-1(7.56±0.90)ng/ml in PeAF group were significantly higher than those of PAF group and control group(P<0.05);②vaspin was significantly and positively correlated with PⅠCP,MMP-1,PⅢNP,TIMP-1 in PAF group and PeAF group.Conclusion Serum vaspin level of AF patients were significantly high and positively correlated with atrial fibrosis biochemical markers,which indicated that serum vaspin level might be closly related to atrial fibrosis in AF patients.It may be a potential marker to identify the degree of fibrosis in atrial fibrillation.

Objective:To evaluate the effects of electroacupuncture (EA) on the learning and memory function of offspring rats exposed to sevoflurane in late-pregnancy.Methods:Thirty-two SPF healthy Sprague-Dawley pregnant rats at gestational day 18, weighing 260-280 g, were assigned to 4 groups ( n=8 each) using a random number table method: control group (C group), sevoflurane group (Sev group), EA group and sham EA group (SEA group). Sev, SEA and EA groups inhaled 2.5% sevoflurane in 50% oxygen for 6 h. In EA group, Shenting, Baihui, bilateral Quchi, and bilateral Zusanli points were stimulated with an electric stimulator (disperse-dense waves, frequency 2/6 Hz, intensity 1 mA, 20 min per day for 7 consecutive days) starting on postnatal day 21, EA was performed again for 7 days after an interval of 1 day, and the EA treatment lasted for a total of 14 days. Moriss water maze test was performed at 36 days of age to detect the spatial learning and memory function. The offspring rats were sacrificed on postnatal day 42, and the hippocampal tissues were removed for calculation of the dendritic spine density of neurons (after Golgi staining) and for determination of the apoptosis rate (using flow cytometry) and the expression of the two primary forms of brain-derived neurotrophic factor (BDNF), mature (mBDNF) and pro (proBDNF), mBDNF/proBDNF ratio, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) (by Western blot). The mBDNF/proBDNF ratio was calculated. Results:Compared with C group, the escape latency was significantly prolonged, the time of staying at the target platform quadrant was shortened, the frequency of crossing the original platform was reduced, the dendritic spine density of hippocampal neurons and mBDNF/proBDNF ratio were decreased, the expression of TrkB was down-regulated, and the expression of p75NTR was up-regulated in Sev groups ( P<0.05). Compared with the offspring rats of Sev and SEA groups, the escape latency was significantly shortened, the time of staying at the target platform quadrant was prolonged, the frequency of crossing the original platform was increased, the dendritic spine density of hippocampal neurons and mBDNF/proBDNF ratio were increased, the expression of TrkB was up-regulated, and the expression of p75NTR was down-regulated in the offspring rats of EA group ( P<0.05), and no significant change was found in the aforementioned parameters in the offspring rats of SEA group ( P>0.05). There was no significant difference in the apoptosis rate of hippocampal neurons among the offspring rats of the four groups ( P>0.05). Conclusions:EA can improve the learning and memory function of offspring rats exposed to sevoflurane in late-pregnancy, and the mechanism may be related to promoting the conversion of proBDNF to mBDNF and improving neuronal development.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Objective:To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro.Methods:The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons.Results:shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells ( P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) ( P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) ( P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Conclusions:SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

Objective To detect ASXL1 gene variants among patients with myelodysplastic syndrome (MDS) and explore their correlation with variants of other genes and clinical features of patients.Methods For 149 patients with MDS,genomic DNA was amplified by PCR and subject to direct sequencing to identify variants of ASXL1,U2AF1,SF3B1,DNMT3A,TET2,IDH1/2,NPM1,FLT3-ITD and C-KIT genes.Results ASXL1 variants were found among 37 patients (24.8％).Other commonly mutated genes included U2AF1 (22.8％),TET2 (11.4％),DNMT3A (9.4％),NPM1 (8.1％) and SF3B1 (6.0％).The frequency of concurrent U2AF1 and TET2 variants among patients with ASXL1 variants was slightly higher than that of wild-type patients.No significant difference was found in median age,MDS subtype,karyotype,peripheral leukocytes,hemoglobin,platelet levels,and bone marrow blast counts between the ASXL1-variant and the wild-type groups (P＞0.05).Twenty-nine patients harboring ASXL1 variants were followed up,37.9％ progressed to acute myeloid leukemia (AML).The rate of transformation in ASXL1-variant group was significantly higher than the wild-type group (37.9 ％ vs.14.1％,P＜0.01).Conclusion ASXL1showed a high frequency of variant among MDS patients,which was frequently accompanied with U2AF1 and TET2 variants.Compared with the wild type group,patients with ASXL1 variants were more likely to progress to AML.

Objective To investigate the prevalence of pulmonary fungal infection and drug resist-ance of the pathogenic fungi among children with severe diseases in pediatric intensive care unit(PICU). Methods From July 2013 to June 2017,the complete clinical data,results of fungal culture and drug sensi-tivity of bronchoalveolar lavage fluid in 112 critically ill children with pulmonary fungus infection of PICU hospitalization in our hospital were collected. Samples of peripheral venous blood were collected meantime, including blood routine examination,C reactive protein,G test and GM test. Results One hundred and twen-ty-six fungi were isolated from sputum samples in 112 critically ill children. Severe pulmonary infection (30. 36%,34/112) was the most common form of the primary diseases, the next were severe sepsis (16. 07%,18/112)and severe malnutrition(15. 18%,17/112). Classified based on age difference,the first one was ＜1 year old (43. 75%,49/112),the second one was 1 to 3 years old(29. 46%,33/112). The fun-gal strains were predominantly Candida albicans (61. 90%) and Candida tropicalis (16. 67%),among the infectious cases 14 were diagnosed as mixed infection. Two cases of 3 cryptococcal infectious children were HIV infection,another one was malignant tumor,Cryptococcus was cultured in both sputum,pleural effusion and cerebrospinal fluid. The drug resistance rate of fluconazol in 126 strains of fungi was 12. 70%,the rate of itraconazole was 7. 14%. Generally,the fungi cultured were with very low resistance to 5-fluorocytosine,vori-conazole and amphotericin B. However,the strains of Aspergillus fumigates,Candida kruse,Candida parapsi-losis and Cryptococcus were highly resistant to fluconazol and itraconazole,but with very low resistance to 5-fluorocytosine and amphotericin B. Conclusion Candida albicans is the main pathogenic fungus of pulmo-nary fungal infection among children in PICU,and we could choose voriconazole and amphotericin B as treat-ment of critically ill children with pulmonaty fungal infection.

Objective To explore the role and effectiveness of flexible fiberoptic brochoscopy ( FFB) in critically ill children with continuous invasive respiratory support. Methods From July 2014 to June 2017,135 critically ill children with severe pneumonia had received continuous invasive respiratory sup-port and undergone FFB in the pediatric intensive care unit( PICU) of our hospital. These patients were en-rolled into the therapy group. Another 104 severe pneumonia patients who had not received FFB were enrolled into the control group. Clinical characteristics of both groups were collected and compared. Results No sig-nificant differences were detected in patients′gender, age, PCIS, usage of antibiotics, and the levels of CRP and PCT assayed at the time of admission to PICU between the therapy group and control group(P>0. 05). The positive rate of bacteria culture of the bronchoscopic lavage was 78. 52％( 106 cases ) in the therapy group,and it was significantly higher than that in the control group(60. 58％,63 cases) (χ2 =5. 681,P <0. 005). For 106 cases in the therapy group,117 bacteria strains were identified,while there were 72 bacteria strains found in 63 cases with positive bacteria culture in the control group. Gram negative bacteria were the most common type,followed by Gram positive bacteria. The third most common pathogenic microbes were fungi,with a significantly higher frequency in the therapy group. No significant differences were found in PaO2 and oxygenation index between both groups before FFB. However,in a half hour after FFB,the PaO2 and oxygenation index significantly increased in the therapy group,and higher than those in the control group (P<0. 005). The levels of CRP and PCT assayed before and the first day after FFB were not significantly changed(P>0. 05). But the levels of CRP and PCT in the therapy group significantly decreased in the third day after FFB,and more than those in the control group. Furthermore,duration of invasive respiratory sup-port,and the stay of PICU were significantly shorter in the therapy group(P<0. 005). Conclusion FFB can play an important role in the collection of pathogenic microbes. It also achieves better results in the treatment of severe pneumonia for children in PICU. Therefore,it is worthwhile to be recommended as a safe and feasi-ble intervention in PICU.

AIM To explore the effects of Sangtong alkaloids (total alkaloids and total flavones from Mori folium,STA) on the random blood glucose,starch tolerance and hepatic insulin resistance in db/db mice with type 2 diabetes mellitus.METHODS Eight-week-old db/db mice were divided into model group (normal saline),acarbose group (39 mg/kg) and Sangtong alkaloids groups (105,210 and 420 mg/kg),db/m mice were used as control group (normal saline).The mice were given by intragastric administration for one hundred days.The random blood glucose of mice was determined every ten days.The starch tolerance was determined in the 100th day,together with the determination of serum insulin level,insulin resistance index and insulin sensitivity index.Histopathology changes of pancreas were observed by HE staining.Protein expressions of P-IRS1,P-PI3 K,P-AKT and GLUT2 were detected by Western blot.RESULTS Sangtong alkaloids significantly decreased the random blood glucose,serum insulin level and insulin resistance index,and increased the insulin sensitivity index in db/db mice.Meanwhile,Sangtong alkaloids ameliorated the pancreas histopathological damage and up-regulated the protein expressions of P-IRS1,P-PI3K,P-AKT and GLUT2 in liver.CONCLUSION Sangtong alkaloids can decrease the random blood glucose and improve the insulin resistance of liver in db/db mice with type 2 diabetes mellitus,whose mechanism may be associated with the regulation of hepatic insulin signal pathway.

Objective To study the changes of neutrophil surface molecule CD64 and inflammatory factor levels in patients with burn infection. Methods 46 cases of patients with burn infection who were treated in the department of burn in our hospital between March 2010 and October 2015 were selected as the observation group. Meanwhile, 46 cases of healthy people who underwent physical examination in our hospital during the same period were included in the control group. The levels of neutrophil surface molecule CD64, C-reactive protein (CRP), white blood cell count (WBC) and inflammatory factor [interleukin IL-6 (IL-6), interleukin (IL-8), tumor necro-sis factor (TNF-α) in the two groups of subjects were determined by flow cytometry and were compared. Results In the observation group, the levels of CD64, CRP, WBC and inflammatory factors were significantly higher than those in the control group (P < 0.05). Conclusion The levels of CD64, CRP, WBC and inflammatory factors in patients with burn infection are significantly higher than those in healthy people , which indicates that neutrophil surface molecule CD64, inflammatory factors and burn infection are closely correlated.