Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

OBJECTIVETo assess the response of aging-related symptom complex to small-dose supplement of growth hormone.

METHODSThirty patients, aged 42 to 77, with aging-related symptom complex and normal serum testosterone were studied. Each subject received growth hormone at the dosage of 0.04 U/kg, 3 times/week for six months. Before and after treatment, body weight, grip strength, abdomen circumference, IPSS, uroflow rate, prostate volume, serum testosterone, cholesterol, triglyceride, PSA, IGF-1, glucose and side effects were determined in every case. Self Rating Scale used by Bosphorus university was adopted.

RESULTSAfter the treatment, the rating scores were significantly improved, grip strength and serum level of IGF-1 increased, and abdomen circumference and serum cholesterol decreased. Whereas, IPSS, uroflow rate, prostate volume, serum testosterone, triglyceride, PSA, glucose and body weight were not significantly changed.

CONCLUSIONSix months treatment with small-dose growth hormone can improve aging-related symptom complex with little adverse effect.

Adult ; Aged ; Aging, Premature ; drug therapy ; Andropause ; Blood Glucose ; metabolism ; Follow-Up Studies ; Growth Hormone ; administration & dosage ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Lipids ; blood ; Male ; Middle Aged ; Prostate-Specific Antigen ; blood

Objective:To discuss the diagnostic value of miR-26a/b and relationship of this microRNA with clinicopathological features in patients with gastric cancer. Methods:The expression of serum miR-26a/b was detected in 121 patients with gastric cancer and 116 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship of miR-26a/b and clinicopathological parameters of patients were analyzed. The receiver operating curve (ROC) was constructed to in vestigate the value of miR-26a/b in the diagnosis of gastric cancer. Results:The relative expression levels of serum miR-26a and miR-26b in patients with gastric cancer were lower than those in the control group (1.60±1.02 vs. 5.35±0.44;1.44±0.71 vs. 5.35±0.71;P<0.05). The relative expression level of miR-26a/b correlated with TNM stage, and the relative expression level of miR-26a also correlated with invasion depth and lymph node metastasis (P<0.05), but not with sex, age, tumor size, or histological type (P>0.05). The area under the ROC curve of miR-26a was 0.828 (95％CI:0.776～0.881), with sensitivity of 73.3％and specificity of 81.0％, while the area under the ROC curve of miR-26b was 0.853 (95％CI:0. 801～0.906), with sensitivity of 68.1％and specificity of 99.2％. Conclusion:The expression of miR-26a/b significantly reduced in patients with gastric cancer, and its expression level correlated with the clinical stage, invasion depth, and lymph node metastasis. MiR-26a/b has potential diagnostic value for gastric cancer.

Objective To study the generating algorithm of personalized external fixation model based on STL file, so as to realize the fabrication of personalized external fixation through 3D scanning, model generation and 3D printing. Compared with the traditional plaster fixation, the external fixation obtained by the proposed method has the advantages of good adhesion to the external surface of the limb, good gas permeability and light weight. Methods In order to generate a personalized external fixation model, the key generating algorithms of the model were studied. The point cloud file of the residual limb was obtained by a 3D scanner, and then was converted into an STL format file. The triangular patches were processed by cutting, offsetting, triangulating and hollowing to create an external fixation model with good gas permeability and conformable surface that is fully fitted with the body surface. Finally, the external fixation was fabricated by 3D printing. Results Using the improved point offset algorithm, the problem of severe distortion of the point offset at the plane and sharp corners was solved. Using the tangent sort method, the points on the contour ring were sorted clockwise to obtain a triangular profile. The hollowing of the model was achieved by using the typical three-dimensional "cutting tool" mathematical model and the STL file space intersection method. Conclusions The improved model generating algorithm was validated based on a wrist case, and the personalized external fixed fixation model with conformable surface was obtained. It is proved that the proposed model generating algorithm is effective and practical.

3D printing technology has unique advantages and broad application prospect in biomedicine field. In recent years, cell printing, tissue printing, and organ printing technologies h have appeared successively, and drug printing and medical device printing have been realized. For complex surgical cases, surgeons and researchers have explored a surgical program that involves 3D printing technology, and completed many clinical applications including case discussions, surgical simulations and implantation surgeries. These efforts promoted the application and development of 3D printing technology in medical field. The purpose of this paper is to describe the application and research status of 3D printing technology in medical field from the aspects of medical teaching, orthopedic surgery, stomatology, bioprinting, drug printing, medical device manufacturing, etc., and put forward the prospects for future development.

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L⁻¹), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L⁻¹ with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L⁻¹ imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L⁻¹ imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.