BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

Background::Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods::We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018).Results::Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted β = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted β = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring’s overall crystallized intelligence. Conclusions::Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.

Gastric cancer ranks fifth in global cancer mortality,which is highly aggressive and heterogeneous.How-ever,the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer.Gastric cancer organoid is a multicellular three-dimensional structure de-veloped in vitro,which can mimic the structure and function of native gastric cancer.Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models,mimicking the tumor microenvironment,high-throughput screening of drugs,discovering new therapeutic targets,predicting clinical therapeutic responses,and guiding individualized treatment.In this paper,the progress of gastric cancer or-ganoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical re-search and supporting the clinical treatment of gastric cancer.

OBJECTIVES: Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo. METHODS: Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene. RESULTS: The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT. CONCLUSION ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
Animals ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; China ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Stomach Neoplasms/genetics*

Objective To establish the fingerprint spectrum and assay three active components (hesperidin, salvianolic acid B and chrysophanol) in Shenshuaining granule by HPLC method. Methods The chromatographic separation was achieved on SunFireTM C₁₈ column with acetonitrile-0.1% formic acid aqueous solution as mobile phase. Gradient elution program was applied with flow rate of 1.0 ml/min, detection wavelength at 254 nm and the column temperature at 25 ℃. The fingerprint spectrum was established and three active components in Shenshuaining granule were assayed. Results There were 22 common peaks on the fingerprints after analyzing chromatograms from 10 batches of Shenshuaining granules. Good fingerprint similarities (≥0.9) between different batches and the control chromatogram were found. This method has great repeatability, stability and precision, which meets all the assay requirements. Conclusion A simple and reliable HPLC method was developed, which is suitable for the fingerprint establishment of Shenshuaining granules. It provides a method for the quality control of Shenshuaining granules.

OBJECTIVE：To identi fy chemical components of Actinidia chinensis root rapidly ，and to provide reference for further material basis and quality control study of the crude medicine. METHODS ：UHPLC-Q-TOF-MS/MS technique was used to detect chemical components of A. chinensis root. The separation was performed on Waters XSelect HSS T 3 column with mobile phase consisted of 0.1％ formic acid acetonitrile solution- 0.1％ formic acid water solution （gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 40 ℃，and sample size was 3 μL. Electrospray ion source was adopted，the data was collected under negative ion mode ；the scanning range was m/z 50-1 500；the drying gas temperature was 350 ℃，the atomizing air pressure was 45 psi，the capillary voltage was 3 500 V，and sheath gas temperature was 350 ℃. According to the information of excimer ion and secondary fragment ion ，the chemical components were identified by combining with the relevant literature ，the retention time of the reference substance and the law of mass spectrometry cracking. RESULTS & CONCLUSIONS ：Totally 58 chemical components was identified ，which included 16 pentacyclic triterpenes （such as hydroxyasiatic acid ，asiatic acid ，maslinic acid，corosolic acid ，oleanic acid ，ursolic acid ，etc.），12 flavonoids（such as rutin ，quercitrin，cynaroside，astragalin，etc.），17 organic acids （such as cryptochlorogenic acid ，chlorogenic acid ，isochlorogenic acid A ，isochlorogenicacid C ，etc.）. There were 9 components（such as procydanidin B 1，B2 and luteolin ，etc.）identified for the first time in A. chinensis root. UHPLC-Q-TOF-MS/ MS technique can be used for the rapid identification of chemical components in A. chinensis root.

Objective To investigate the extraction methods for active components from oral ulcer film and optimize the determination methods of active components dexamethasone sodium phosphate and metronazole. Methods Different extraction solvents(methanol, water and 70% methanol aqueous) were applied to extract the active components dexamethasone sodium phosphate and metronazole from oral ulcer film, which contents were quantified by a HPLC method. Results the extraction solvent water had the best efficacy and more simpler compared to the other two solvents. Clotriazole showed a good linear relationship within 5.014 5-200.5800 μg/ml (r=0.999 8), and the average extraction recovery was (104.23±0.63)%, and for dexamethasone sodium phosphate, a good linear relationship was obtained in the range of 0.482-16.328 μg/ml (r=0.9999), and the average extraction recovery was (103.97±1.02)%. Conclusion The water extraction method established in this study was simple and efficient, which showed features of simplicity, accuracy and repeatable.

Objective To explore the long-term effectiveness of using extracorporeal shock waves in the treatment of plantar fasciitis. Methods Extracorporeal shock wave therapy was applied to 23 plantar fasciitis suffer-ers once a week for three weeks. MRI examinations were performed before and 4 hours after the first treatment. Before the treatment and one month after it was complete, all of the patients rated their pain using a visual analogue scale ( VAS) , and their infirmity was quantified using a heel tenderness index ( HTI) and the ankle-hind foot scale of the American Orthopaedic Foot and Ankle Society ( AOFAS) . The longest walking time was also recorded. Paired t-tests compared the T2 values of the fascia, muscles and fat pads, the longest walking time and the VAS scores before and after the treatment. Pearson correlation coefficients were evaluated to test the significance of any correlation between the T2 changes and the changes in the VAS scores. Results After the shock wave therapy, the average VAS, HIT and AOFAS scores had significantly decreased, while the longest walking time had increased significantly. The mag-netic resonance imaging showed increased edema in the fascia and their surrounding soft tissues. And the extent and degree of the T2 weighted high signal increased four hours after the treatment. The changes in the T2 values correlated positively and significantly with the changes in the VAS scores. Conclusion Extracorporeal shock waves have an excellent therapeutic effect on plantar fasciitis. They can significantly relieve heel pain and improve foot movement.

Objective: To explore the safety of liver transplantation recipients with Rh blood group mismatchming. Methods: From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation. Results: At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all P>0.05); Also, no significant difference existed in the incidence of infection, vascular complications or acute rejection(all P>0.05). In Rhmismatch group, 4 recipients received Rh(+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation. Rh(D) antibody was negative at all timepoints. Conclusions Taking into account the rarity of Rh-negative blood group in Chinese, it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available.

Objective: To explore the application value of quantitative evaluation on liver function in patients with hepatitis B cirrhosis based on texture features of liver parenchyma from high frequency ultrasound images. Methods: Two-dimensional high-frequency ultrasonograms of liver parenchyma in 95 patients with different levels of liver function (37 cases in Child-Pugh A group, 33 in Child-Pugh B group and 25 cases in Child-Pugh C group) and 21 healthy volunteers (control group) were collected. Based on the idea of machine learning, the defect detection method of computer technology was used to locate the defect in liver parenchyma images, and the defect maps of liver parenchyma were obtained. Then three parameters, i.e. the maximum number per unit area of defect maps x(D), the mean value of defect maps mean (D) and the entropy of defect maps ε(D) were extracted. The differences of three parameters among different groups were compared. Results: There were significant differences of x(D), mean (D) and ε(D) among 4 groups (all P<0.001). The value of x(D) and mean (D) in Child-Pugh A group, B group and C group were higher than those in control group (all P<0.05). The value of mean (D) in Child-Pugh A group and Child-Pugh B group were higher than that in control group (both P<0.05). The value of mena (D) and ε(D) in Child-Pugh B group were higher than those in Child-Pugh C group (both P<0.05). Conclusion: Texture features analysis of liver parenchyma based on high-frequency ultrasonic images can accurately assess liver cirrhosis with Child-Pugh A and Child-Pugh B, while the evaluation of liver cirrhosis with Child-Pugh C still needs to combine with other features of the liver.