Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To investigate the clinical efficacy of Yiqi Yangyin decoction combined with metformin and irbesartan in treating type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. Methods:A case-control study was performed to retrospectively analyze the clinical data of 92 patients with type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. These patients received treatment at the First People's Hospital of Huzhou from February 2021 to April 2023. They were divided into two groups, with 46 patients in each group, based on different treatment methods. The control group received metformin and irbesartan, while the observation group was treated with Yiqi Yangyin decoction in addition to the treatment provided to the control group. Both groups underwent treatment for 1 month. The clinical efficacy of the two groups was evaluated, and the changes in traditional Chinese medicine symptom scores, blood glucose levels, blood pressure, and the occurrence of adverse reactions were compared between the two groups before and after treatment. Results:The total response rate of the observation group was 93.48% (43/46), which was significantly higher than that of the control group [82.61% (38/46), χ2 = 5.63, P < 0.05). After treatment, the traditional Chinese medicine symptom score for the observation group was (9.43 ± 2.11) points, which was significantly lower than that of the control group [(12.11 ± 2.32) points, t = 11.34, P < 0.001]. The fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin levels in the observation group were (7.51 ± 1.34) mmol/L, (9.06 ± 2.11) mmol/L, and (6.23 ± 0.76)%, respectively, all of which were significantly lower than those in the control group [(8.75 ± 2.12) mmol/L, (11.15 ± 2.43) mmol/L, (7.11 ± 1.02)%, t = 4.13, 6.14, 4.01, all P < 0.05]. The systolic blood pressure in the observation group was (125.48 ± 8.14) mmHg (1 mmHg = 0.133 kPa), which was significantly lower than that in the control group [(131.32 ± 9.22) mmHg, t = 6.76, P < 0.001]. The difference in the incidence of adverse reactions between the two groups was not statistically significant ( P > 0.05). Conclusion:Yiqi Yangyin decoction combined with metformin and irbesartan is highly effective in treating type 2 diabetes complicated by hypertension with qi and yin deficiency syndrome. This combined therapy can effectively lower the traditional Chinese medicine symptom score, improve patients' blood glucose and blood pressure levels, and has a low incidence of adverse reactions.

Objective:To investigate the correlation between serum forkhead box protein P1 (FOXP1) and cyclin-dependent kinase2 (CDK2) and bone mineral density in perimenopausal women with osteoporosis (OP) .Methods:A total of 80 perimenopausal women treated in our hospital from Feb. 2021 to Aug. 2022 were selected as study objects. Among them, 38 were in the OP group and 42 were in the control group. The expression levels of FOXP1 and CDK2 in serum were detected by ELISA. BMD expression levels of lumbar spine (L1-L4) and femoral neck were measured by DEXA BMD analyzer. The correlation between serum FOXP1 and CDK2 and bone mineral density in perimenopausal women with osteoporosis was analyzed by Pearson method.Results:Compared with the control group, the contents of FOXP1 and CDK2 in serum of the control group were (42.94±3.37) pg/ml and (102.46±12.247) pg/ml, respectively. Serum FOXP1 and CDK2 contents in OP group were (25.91±4.38) pg/ml and (60.59±10.777) pg/ml, respectively. Compared with the control group, serum FOXP1 and CDK2 expression levels and bone mineral density of lumbar spine (L1-L4) and femoral neck in OP group were significantly decreased. The BMD of lumbar spine (L1-L4) and femoral neck of women in the control group were 0.68±0.28 and 0.43±0.99, respectively. BMD of lumbar spine (L1-L4) and femoral neck of women in the OP group were 0.40±0.10 and 0.21±0.15, respectively. Bone mineral density decreased in the lumbar spine (L1-L4) and femoral neck in the OP group. The differences were statistically significant ( P<0.05). In addition, the correlation analysis results showed that the expression level of FOXP1 in serum was positively correlated with bone mineral density of lumbar spine (L1-L4) and femoral neck ( r=0.546, 0.245, P<0.05), and the expression level of CDK2 was positively correlated with bone mineral density of lumbar spine (L1-L4) ( r=0.600, P<0.05) . Conclusions:In perimenopausal women with osteoporosis, the expression of FOXP1 and CDK2 in serum was significantly decreased, and there was a correlation with bone mineral density. It is suggested that FOXP1 and CDK2 may be used as biological indicators and clinical predictors of osteoporosis in perimenopausal women.

In the current scientific research training of the academic postgraduate students majoring in clinical laboratory diagnostics, there are many problems including insufficient scientific research level, poor scientific research environment and so on. Based on many years of experience on cultivating postgraduate students and starting from the five factors of 4M1E (man, machine, material, method and environment) method, a scientific strategy is proposed, and then the scientific research ability and level of academic postgraduate students majoring in clinical laboratory diagnostics could be improved by exerting its own self-motivation, strengthening the guidance of tutors, improving training tools, heightening scientific thinking, and enhancing environmental friendliness of scientific research.

Objective:To detect the mRNA expression and methylation status of leucine rich repeat containing 55(LRRC55) gene in pancreatic carcinoma tissues, and discuss the clinical value.Methods:Resected pancreatic ductal adenocarcinoma and normal adjacent specimens from 37 patients admitted in General Surgery of First Affiliated Hospital of Naval Medical University were collected from May 2019 to May 2021. Another two normal pancreas specimens and two blood samples from healthy adults were also collected. All patients′ age, gender, tumor location, tumor size, tumor differentiation, TNM staging, lymphatic metastasis, CEA and CA19-9 level were recorded. Bisulfite treatment of genomic DNA and sequencing analysis was used to study methylation patterns in CpG islands of the promoter for LRRC55 gene in fresh tissues from 2 pancreatic adenocarcinoma and adjacent tissues, 2 normal pancreatic tissues, 2 pancreatic cancer cell lines (PaTu8988 and ASPC1). LRRC55 mRNA in 35 pancreatic adenocarcinoma and adjacent tissues was detected by real-time quantitative PCR and the correlations with clinical parameters were analyzed.Results:CpG islands of LRRC55 in pancreatic adenocarcinoma tissues and pancreatic cancer cell lines was highly methylated and the mean methylation rate was 53% and 71%, respectively; while LRRC55 gene in pancreatic adjacent tissues and normal pancreatic tissues was lowly methylated, and the mean methylation rate was 8% and 11%. The relative expression in the pancreatic adenocarcinoma tissues and the paired adjacent normal tissues was 0.21 (0.02, 1.00 ) and 0.98 (0.33, 3.66 ), respectively; the former was significantly lower than the later and the difference was statistically significant ( P=0.003). Correlation analysis showed that LRRC55 mRNA expression level was related to tumor differentiation and CEA, but not correlated with patients′ age, gender, tumor location and size, CA19-9 level, lymphatic metastasis and TNM staging. Conclusions:Pancreatic cancer tissue and cell lines had abnormal methylation of LRRC55 gene; LRRC55 gene hypermethylation was related with its lower mRNA expression level in pancreatic cancer, which was correlated with the tumor differentiation and CEA level. LRRC55 may be a potential suppressor gene for pancreatic cancer.

Objective:To investigate the effect of the completion time of initial 30 mL/kg fluid resuscitation on the prognosis of patients with septic shock.Methods:An observational study was conducted. The inpatients with septic shock admitted to intensive care unit (ICU) of Northern Jiangsu People's Hospital, Affiliated Hospital of Yangzhou University and Jiangdu People's Hospital from October 1st, 2018 to September 30th, 2020 were enrolled. The general data including gender, age, body mass index (BMI), patient source, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and arterial blood lactic acid (Lac) at ICU admission, fluid resuscitation dose, completion time of initial 30 mL/kg fluid resuscitation, mechanical ventilation, incidence of acute kidney injury (AKI), continuous renal replacement therapy (CRRT), length of ICU stay and 28-day mortality. The relationship between the completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score (the difference between SOFA score 3 hours of fluid resuscitation and initial SOFA score) was analyzed. In addition, according to the completion time (T) of initial 30 mL/kg fluid resuscitation, the patients were divided into T ≤ 1 hour group, 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group, and the observation parameters among the groups were compared.Results:① A total of 131 patients were enrolled, including 94 males and 37 females with an average age of (68.3±15.0) years old. The median APACHE Ⅱ score was 27 (21, 34), the median of initial SOFA score was 12 (10, 14), the median of initial Lac was 5.0 (3.4, 7.1) mmol/L, and the most common source of infection was lung, with a total of 87 patients (66.41%). The completion time of initial 30 mL/kg fluid resuscitation and ΔSOFA score fitted the Logistic curve ( Y = -1.062 6 X2+4.407 9 X+0.961 8), which suggested that the early or late completion time of initial fluid resuscitation had adverse effects on the prognosis of patients with septic shock.② There was no significant difference in infection site, initial APACHE Ⅱ score, initial Lac, and initial SOFA score among different completion time of initial 30 mL/kg fluid resuscitation groups. The respiratory support rate, the incidence of AKI and the ratio of CRRT in the T ≤1 hour group were significantly higher than those in the 1 hour < T≤2 hours group, 2 hours < T≤3 hours group and T > 3 hours group (respiratory support rate: 78.57% vs. 75.51%, 42.86%, 75.00%; incidence of AKI: 57.14% vs. 20.41%, 21.43%, 50.00%; ratio of CRRT: 35.71% vs. 0%, 7.14%, 16.67%), the differences among the groups were statistically significant (all P < 0.05). The 28-day mortality was the highest in the T ≤ 1 hour group (64.29%), and the lowest in the 1 hour < T ≤2 hours group (22.45%), 35.71% in the 2 hours < T ≤ 3 hours group, 33.33% in the T > 3 hours, and the difference among the groups was statistically significant ( P < 0.01). Conclusions:Completion of initial 30 mL/kg fluid resuscitation in 1-2 hours after septic shock may reduce the 28-day mortality and improve organ dysfunction, and initial fluid resuscitation prematurely or too late may increase 28-day mortality. But further research and verification are needed.

AIM: To observe the anti-inflammatory effect of CQMUH-011 and to explore its mechanism.METHODS: Three kinds of animal models, mouse ear swelling induced by xylene, rat granuloma induced by cotton ball and rat rheumatoid arthritis induced by Freund's complete adjuvant, were established to study the anti-inflammatory effect of CQMUH-011.The ear swelling degree, dry weight of cotton ball granuloma, arthritis index, paw swelling and ankle joint pathological changes were measured to reflect the severity of inflammation.The anti-inflammatory mechanisms of CQMUH-011 were investigated by detecting the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by ELISA.Malondialdehyde (MDA), myeloperoxidase (MPO) and nitric oxide (NO) were determined by corresponding kits.RESULTS: Treatment with CQMUH-011 significantly decreased TNF-α, IL-6 and NO concentrations, MDA contents and MPO activity in the serum.Meanwhile, Ear swelling degree, dry weight of cotton ball granuloma, arthritis index, paw swelling and ankle joint pathological damage were attenuated.CONCLUSION: CQMUH-011 has an anti-inflammatory effect, which may be related to inhibiting the production of inflammatory factors and attenuating lipid peroxidation.

Objective To compare the clinical value of three-dimensional dynamic contrast enhanced magnetic resonance angiography (3D DCE MRA) and digital subtraction angiography (DSA) in diagnosing inferior vena cava diseases in suspected case of Budd-Chiari syndrome (BCS).Methods Radiological findings of 91 suspected BCS cases obtained from 3D DCE MRA and DSA in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed.DSA test was considered as golden standard,which assess the capacity of 3D DCE MRA in diagnosing inferior vena cava diseases,including sensitivity,specificity and accuracy.Kappa test was utilized to compare the coincidence ratio of 3D DCE MRA and DSA in diagnosing inferior vena cava diseases.Results Among 91 suspected BCS cases with 3D DCE MRA,a total of 17 cases without inferior vena cava diseases were misdiagnosed as inferior vena cava stenosis,two patients with inferior vena caval obstruction was misdiagnosed as falsely negative.Seventy-two patients with 3D DCE MRA were confirmed via DSA in diagnosing inferior vena cava diseases,sensitivity was up to 97.7％ (58/60),false positivity 54.8％ (17/31),specificity 45.2％ (14/31),respectively.Fair coincidence ratio of 3D DCE MRA and DSA in diagnosing inferior vena cava diseases (Kappa =0.474,P ＜ 0.05).Conclusions There could be clinical value of 3D DCE MRA for its high sensitivity and low specificity in diagnosing inferior vena cava diseases,and favorable coincidence ratio was discovered between 3D DCE MRA and DSA.Comprehensive consideration is needed for suspected cases of inferior vena cava stenosis detected by 3D DCE MRA,and further analysis may figure out potential causes of misdiagnosis and decline false positive events.

Objective To study the clinical significance of the caudate lobe vein in patients with Budd-Chiari syndrome (BCS) by contrast-enhanced magnetic resonance imaging(MRI).Methods Contrast-enhanced MRI data of 46 patients with BCS, 30 patients with cirrhosis due to hepatitis B virus (HBV) and 49 healthy people in our institution were analyzed retrospectively.The presence and diameter of the caudate lobe vein among the three groups were measured.Among the BCS group, in which the caudate lobe vein could be seen, andpatients were divided into two groups according to disease duration and patency of inferior vena cava (IVC), respectively.And comparative study of diameter between two groups was performed.Results ①The caudate lobe vein was noted in 76.1% of patients with BCS, in 30.0% of patients with cirrhosis due to HBV,and in 36.7% of healthy subjects.The diameter of caudate lobe vein in BCS group was larger than that in both cirrhosis group and healthy group(P<0.01).There was no statistically difference between cirrhosis group and healthy group(P>0.05).②Among BCS group,the caudate vein was shown in 35 patients, with mean diameter of(4.21±1.66)mm.For 35 BCS,the diameter of caudate lobe vein in chronic group was larger than that in acute group(P<0.05).The diameter of caudate lobe vein in IVC obstruction group was larger than that in IVC open group(P<0.05).Conclusion The demonstration of the caudate lobe vein on contrast-enhanced MRI is of great significance in the diagnosis and treatment of BCS.

Objective To evaluate the value of serum uric acid(UA)levels with reference to the age,waist circumference,and body mass index(BMI)in predicting the metabolic syndrome(MS)in obese children.Methods A total of 300 obese children,including 180 boys and 120 girls,were enrolled in this study.The height,BMI,waist and hip circumference,blood pressure,serum glucose,insulin and lipid profile in all participants were measured.Oral glucose tolerance test and insulin releasing test were performed.The boys or girls were divided into 4 groups according to the 4 quantile of UA level,respectively.The clinical characteristics and correlation of UA with the clinical indexes and MS components were compared.The binary Logistic regression analysis was applied in the risk of MS and its components for the 4 groups of obese children.The area under the receiver operating characteristic curve(ROC curve)of UA level,age,waist circumference and BMI were used to predict the MS.Results UA level was increased with the increase of age,waist circumference and BMI,and the UA level was significantly correlated with triacylglycerol,postprandial 2 h glucose(2 h PG)(r=0.196,0.174 in boys;r=0.291,0.179 in girls).In boys,the adjusted odds ratio and 95％CI of the highest quartile of UA for triglyceridemia was 2.71(95％CI:0.77-9.58);which in girls,the adjusted odds ratio and 95％CI of the highest quartile of UA for hyperglycemia,hypertension were 8.45(95％CI:1.76-40.52)and 3.93(95％CI:0.66-23.33),respectively,with significant differences.In boys,the area under the ROC curve of UA level,age,waist circumference and BMI which predict the MS were 0.652 0.626,0.621,0.62,respectively,and the differences were significant(all P<0.05).Conclusions The UA level is significantly correlated with the composition of MS,UA detection combining with reference to the age,waist circumference,and BMI is helpful for the identification of high risk groups of metabolic syndrome.