The mechanism of modified Gan Cao Fu Zi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and experimental validation / 药学学报

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.

Screening of anti-SARS-CoV-2 ligands from Chinese herbs based on a dual-target surface plasmon resonance biosensor / 药学学报

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (KD) of daidzin and ACE2 was 5.18 μmol·L-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.

Identification of constituents in vitro and blood-absorbed ingredients of protective effect on acute liver injury from Yin Chen Hao decoction based on UPLC-QTOF/MS / 药学学报

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Effects of specimen preservation and transportation on blood paraquat concentration in rats / 中华劳动卫生职业病杂志

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.

Association between Serum Uric Acid and the Early Marker of Kidney Function Decline among Chinese Middle-Aged and Older Population: Evidence from the China Health and Retirement Longitudinal Study / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the association between serum uric acid (SUA) and kidney function decline.@*METHODS@#Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m 2. Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines.@*RESULTS@#A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline.@*CONCLUSION@#The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.

Advances on pentraxin 3 in osteoporosis and fracture healing / 中国骨伤

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.

Effect of miR1290 on the growth of endometrial cancer and the related mechanism / 中华肿瘤杂志

Objective: To explore the expression of miR1290 in endometrial cancer tissues and its relationship with the pathological grade, and to find out the effect of miR1290 on biological characteristics of endometrial cancer cells and its mechanism. Methods: A total of 38 cases of endometrioid adenocarcinoma tissues, 10 cases of adjacent tissues and 23 cases of normal endometrial tissues were collected in Provincial Hospital Affiliated to Shandong University from May 2020 to October 2020. The expression of miR1290 was detected by reverse transcription polymerase chain reaction (RT-PCR). The expressions of miR1290 in endometrial cancer cells including KLE and Ishikawa were knocked down by lentiviral transfection. Cell counting kit 8 (CCK-8) test and colony formation test were used to detect cell proliferation ability, wound healing and Transwell test were used to detect cell invasion and migration ability, western blot was used to detect the expressions of epithelial-mesenchymal transition (EMT), phospholipids acylinositide 3-kinase (PI3K)/Akt and Wnt/β-catenin pathway related proteins. Results: The relative expressions of miR1290 in endometrial cancer tissues were 5.40±3.20, which was 1.55 times of normal endometrial tissues (P<0.01) and 1.75 times of adjacent tissues (P<0.01). The relative expressions of miR1290 in 17 cases of endometrial tissues at proliferative stage and 6 cases of endometrial tissues at secretory stage were 3.00±1.08 and 4.97±0.58, respectively, and the difference was statistically significant (P<0.01). In KLE cells and Ishikawa cells, the expression of miR1290 in miR1290 knockdown (Sh-miR1290) group was decreased when compared with the negative control (Sh-NC) group. The absorbance value of Sh-miR1290 group detected by the CCK-8 method and the colony formation rate detected by the colony formation experiment were both increased, the number of cells penetrating the basement membrane in the Transwell experiment and the wound healing rate in the scratch experiment were decreased (P<0.05). In KLE cells, knockdown of miR1290 reduced the expressions of EMT-related proteins including N-cadherin, Vimentin, Snail and Slug(P<0.05), and the expressions of PI3K and P-Akt/Akt (P<0.05), while there was no significant change in the expressions of Wnt and β-catenin (P>0.05). In Ishikawa cells, knockdown of miR1290 decreased the expressions of EMT-related proteins including N-cadherin, Snail and Slug, and the expressions of Wnt and β-catenin, increased the expression of E-cadherin (P<0.05), while there was no significant change in the expressions of PI3K and P-Akt/Akt (P>0.05). Conclusions: The expressions of miR1290 in endometrial cancer tissues are higher than that in the adjacent tissues and normal endometrial tissues. Knockdown of miR1290 expression can promote the proliferation of endometrial cancer cells, but inhibit cell invasion, migration and EMT ability through the PI3K/Akt and Wnt/β-catenin pathways.

Survey on visual acuity and refractive status of preschool children in Xining City, Qinghai Province / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:A total of 1 084 preschool children in 4 kindergartens in Xining City were surveyed on their visual acuity and refraction status to find out abnormal vision and refraction beyond the normal range. METHODS: A cross-sectional survey study. The overall sampling method was used on October 2019, a total of 1 084 preschool children aged 3-6 years were selected from a kindergarten in the east, west, south and north of Xining City. The children were checked for uncorrected distance vision and refractive status was checked by using a refractive screener.RESULTS: The detection rate of abnormal vision in preschool children in Xining City was 12.21%, and the detection rate of abnormal vision increased with the increasing age(χ2lineartrend=94.40, P&#x003C;0.05), and there were differences among different age groups(χ2=293.55, P&#x003C;0.05). Refractive abnormalities accounted for 6.09% of the total number of examinations. With the increasing age, the proportion of compound hyperopic astigmatism decreased(χ2lineartrend=1.79, P&#x003E;0.05).CONCLUSION: The abnormal visual acuity of preschool children in Xining City gradually increases with the increasing age; The refractive state is dominated by astigmatism, among which the proportion of mixed astigmatism and pure myopia astigmatism is the highest, followed by pure hyperopic astigmatism and compound hyperopic astigmatism; With the increase of age, the diopter of compound hyperopic astigmatism gradually decreases, which is in line with the law of children's eye refractive development.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation / 中国天然药物

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

Molecular interactions between the main components of Shuanghuanglian injection and ciprofloxacin injection based on self-assembly / 药学学报

The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.

Mechanism of rhein inhibition of colorectal cancer through arginine metabolism based on protein chip / 药学学报

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.

Evaluation of interaction of chlorogenic acid and cefotaxime sodium based on sequential analysis / 药学学报

The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.

A CCCG-HB-2016 regimen in the treatment of hepatoblastoma in children / 中华普通外科杂志

Objective:To evaluate the clinical efficacy of multi-disciplinary single center's CCCG-HB-2016 regimen in the treatment of hepatoblastoma (HB) in children.Methods:Clinical data of 36 HB patients treated with CCCG-HB-2016 program from Aug 2016 to March 2020 were analyzed.Results:These 36 patients included 20 boys and 16 girls. The serum AFP was all higher than 2 792 ng/ml,there was a correlation between AFP and tumor risk stratification ( H=14.973, P<0.05). Twenty eight cases (77.78%) were epithelial type and 8 cases (22.22%) were mixed epithelial mesenchymal type.All children were treated by tumor resection combined with chemotherapy, and there was a correlation between tumor risk stratification and surgical resection of liver lobe ( H=8.847, P<0.05). The probability of bone marrow suppression in the low-risk group was 58.33% (35/60),that in the intermediate-risk group was 73.49% (61/83) and in the high-risk group was 80.23% (69/86).All 36 cases were followed up to March 31, 2020,with an average follow-up of 21.9 months and the median survival was 22.5 months.The overall survival rate (OS) and event-free survival rate (EFS) were 97.2% and 83.3% respectively. Conclusions:The multidisciplinary CCCG-HB-2016 regimen was with a high success rate and along with a high incidence of bone marrow suppression.

Spongiosum-combined glanuloplasty reduces glans complications after proximal hypospadias repair / 亚洲男科学杂志(英文版)

We aim to design a new glanuloplasty procedure combined with spongiosum to reduce the incidence of glans dehiscence and coronal fistula after proximal hypospadias repair. Patients who underwent urethroplasty by dorsal preputial island flap for proximal hypospadias between January 2014 and December 2016 were reviewed in this retrospective cohort study. Those who underwent spongiosum-combined glanuloplasty comprised the new-maneuver group, whereas those who underwent conventional glanuloplasty comprised the control group. The incidence of complications was then compared. In the new-maneuver group, dysplastic corpus spongiosum alongside lateral Buck's fascia (0.3-0.4 cm wide) on both sides of the urethral plate was separated from the proximal normal spongy tissue, joining into the glans wings to increase tissue volume and covering the neourethra in the glans penis. In the control group, the neourethra was covered with superficial fascia under the coronal sulcus. As a result, the new-maneuver and control groups comprised 47 and 28 patients, respectively. In the new-maneuver group, no glans dehiscence was detected; however, two (4.3%) patients had coronal fistula, two (4.3%) had urethral stricture, and four (8.5%) had diverticulum. In the control group, two (7.1%) patients had glans dehiscence, eight (28.6%) had coronal fistula, four (14.3%) had urethral stricture, one (3.6%) had diverticulum, and one (3.6%) had penile curvature recurrence. The new-maneuver group had less incidences of coronal fistula (P < 0.001), glans dehiscence (P = 0.033), and urethral stricture (P = 0.008) but had a higher incidence of diverticulum than the control group (P = 0.040). It clearly demonstrates that spongiosum-combined glanuloplasty can significantly reduce the incidences of coronal fistula and glans dehisce.

Effects of Jiaotai Pills on CUMS-induced depression model in mice based on changes of SIRT1 expression in hippocampus / 中国中药杂志

The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1β, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1β, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.

Scr eening of key genes and pathways of brain aging and prediction of potential effective Chinese medicinals: based on bioinformatics / 中国中药杂志

Microarray data of hippocampal tissue(HC) of the cognitively intact elderly(60-99 years old) were compared with those of the middle-aged and the young(20-59 years old) by bioinformatics techniques to initially screen out differentially expressed genes(DEGs) and then predict potential effective Chinese medicinals for the treatment of brain aging. The gene expression profile(accession: GSE11882) was downloaded from the Gene Expression Omnibus(GEO) and DEGs were screened based on R package. The key DEGs were identified by STRING, Cytoscape and the plug-in, followed by Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Then the key genes and the medical ontology information retrieval platform(Coremine Medical) were mapped against each other to single out the Chinese medicinals for the treatment of brain aging and construct the " Chinese medicinal-active constituent-target" network. Among the resultant 268 DEGs(246 down-regulated and 22 up-regulated), the 15 key genes were mainly involved in biological processes such as leukocyte migration, neutrophil activation, cell chemotaxis, microglia activation and response to external stimulus, and pathways such as inflammatory process, immune response, cytokine-cytokine receptor interaction, PI3 K-Akt signaling pathway, Rap1 signaling pathway, chemokine signaling pathway and Toll-like receptor signaling pathway. The potential effective Chinese medicinals were Notoginseng Radix et Rhizoma, Ginseng Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma and Astragali Radix. The analysis of DEGs and key genes enhances the understanding of the mechanisms of brain aging. This study provides potential gene targets and ideas for the development of Chinese medicine for brain aging.

Effectiveness of integrated schistosomiasis control in Changzhou City from 2015 to 2020 / 中国血吸虫病防治杂志

Objective To evaluate the effectiveness of the integrated schistosomiasis control measures in Changzhou City from 2015 to 2020, so as to provide insights into the formulation of the strategy used to consolidate the schistosomiasis elimination achievements. Methods The annual schistosomiasis control working report and integrated schistosomiasis control data were collected in Changzhou City from 2015 to 2020, and the prevalence of Schistosoma japonicum infections in humans and livestock and snail status were analyzed to evaluate the effectiveness of the integrated schistosomiasis control measures. Results During the period from 2015 to 2020, a total of 112 061 person-time individuals received serological tests for S. japonicum infections in Changzhou City, and the sero-prevalence was 0.15% to 1.09% during the 6-year period, with a significant difference seen among years (χ2 = 288.11, P < 0.05). From 2015 to 2020, a total of 13 435 person-time individuals received stool examinations, with no egg-positives identified; among 5 840 herd-time livestock receiving schistosomiasis examinations, no positives were detected, while a 100% coverage of fencing livestock was seen each year. During the 6-year period, a total of 38.40 hm2 snail habitats were found, including 8.97 hm2 emerging snail habitats, and among the 2 344 snails dissected, no S. japonicum infection was found. Chemical treatment covered an area of 385.71 hm2, and environmental improvements covered an area of 200.39 hm2. The mean density of living snails was less than 0.1 snails/0.1 m2 in snail habitats found in Changzhou City each year from 2015 to 2020, and the coverage of harmless toilets was 100% in 2020. During the 6-year period, a total of 3.740 6 million person-time individuals were given schistosomiasis health education in Changzhou City. Conclusions Changzhou City is now at the post-elimination surveillance stage; however, there are still factors affecting schistosomiasis transmission. The schistosomiasis surveillance system remains to be improved to consolidate the schistosomiasis elimination achievements in Changzhou City.

Clinical significance of the deep learning algorithm based on contrast-enhanced CT in the differential diagnosis of gastric gastrointestinal stromal tumors with a diameter ≤ 5 cm / 中华胃肠外科杂志

Objective: Contrast-enhanced CT is an important method of preoperative diagnosis and evaluation for the malignant potential of gastric submucosal tumor (SMT). It has a high diagnostic accuracy rate in differentiating gastric gastrointestinal stromal tumor (GIST) with a diameter greater than 5 cm from gastric benign SMT. This study aimed to use deep learning algorithms to establish a diagnosis model (GISTNet) based on contrast-enhanced CT and evaluate its diagnostic value in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before surgery. Methods: A diagnostic test study was carried out. Clinicopathological data of 181 patients undergoing resection with postoperative pathological diagnosis of gastric SMT with a diameter ≤ 5 cm at Department of Gastrointestinal Surgery of Renji Hospital from September 2016 to April 2021 were retrospectively collected. After excluding 13 patients without preoperative CT or with poor CT imaging quality, a total of 168 patients were enrolled in this study, of whom, 107 were GIST while 61 were benign SMT (non-GIST), including 27 leiomyomas, 24 schwannomas, 6 heterotopic pancreas and 4 lipomas. Inclusion criteria were as follows: (1) gastric SMT was diagnosed by contrast-enhanced CT before surgery; (2) preoperative gastroscopic examination and biopsy showed no abnormal cells; (3) complete clinical and pathological data. Exclusion criteria were as follows: (1) patients received anti-tumor therapy before surgery; (2) without preoperative CT or with poor CT imaging quality due to any reason; (3) except GIST, other gastric malignant tumors were pathologically diagnosed after surgery. Based on the hold-out method, 148 patients were randomly selected as the training set and 20 patients as the test set of the GISTNet diagnosis model. After the GISTNet model was established, 5 indicators were used for evaluation in the test set, including sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operating curve (AUC). Then GISTNet diagnosis model was compared with the GIST-risk scoring model based on traditional CT features. Besides, in order to compare the accuracy of the GISTNet diagnosis model and the imaging doctors in the diagnosis of gastric SMT imaging, 3 radiologists with 3, 9 and 19 years of work experience, respectively, blinded to clinical and pathological information, tested and judged the samples. The accuracy rate between the three doctors and the GISTNet model was compared. Results: The GISTNet model yielded an AUC of 0.900 (95% CI: 0.827-0.973) in the test set. When the threshold value was 0.345, the sensitivity specificity, positive and negative predictive values of the GISTNet diagnosis model was 100%, 67%, 75% and 100%, respectively. The accuracy rate of the GISTNet diagnosis model was better than that of the GIST-risk model and the manual readings from two radiologists with 3 years and 9 years of work experience (83% vs. 75%, 60%, 65%), and was close to the manual reading of the radiologist with 19 years of work experience (83% vs. 80%). Conclusion: The deep learning algorithm based on contrast-enhanced CT has favorable and reliable diagnostic accuracy in distinguishing gastric GIST with a diameter ≤ 5 cm and other gastric SMT before operation.