Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

ObjectiveTo analyze the clinical and epidemiological characteristics of confirmed cases of human monkeypox infection in Changning District， Shanghai， and to explore their clinical and epidemiological characteristics. MethodsClinical data from 10 reported cases of monkeypox in individuals residing in Changning District or identified by local medical institutions between July 20 and September 30， 2023， were collected. Epidemiological case investigations were conducted， and throat swabs， anal swabs， and rash swabs were collected by the treating medical institutions. Real-time fluorescence quantitative PCR was used for monkeypox virus nucleic acid testing， and descriptive epidemiological analysis was applied to analyze the epidemiological characteristics of the cases. ResultsAll 10 confirmed cases of human monkeypox infection were all young males with an average age of 35.4 years， all of whom belonged to the men who have sex with men （MSM） population， with no occupational clustering. The primary clinical symptoms included fever， rash， enlarged inguinal lymph nodes， and muscle soreness. Nine cases presented with a rash， and seven cases experienced fever symptoms. Among the 10 cases， one experienced fever， rash， enlarged lymph nodes， and muscle soreness； two had fever， rash， and enlarged lymph nodes； two had fever， rash， and systemic soreness； two had only a rash； one had fever or rash； and one was asymptomatic. Among the nine cases with a rash， the rash was mainly localized to the genital or anal area， with fewer cases presenting rashes on the limbs or trunk simultaneously. All cases reported a history of non-exclusive MSM behavior within 21 days before the onset of the disease. The interval between the last suspected high-risk exposure and the onset of symptoms was 4 to 10 days， with an average interval of 6.9 days. The time from the onset of fever to the appearance of a rash was 0 to 5 days， with an average of 1.87 days. ConclusionThe main clinical manifestations of human infection with monkeypox are fever， rash， and enlarged inguinal lymph nodes. The MSM population is a high-risk group for monkeypox infection， and its source of infection may be associated with MSM exposure. Early-stage symptoms are mild， leading to potential underdiagnosis. Additionally， patients may conceal information during the investigation process， which increases the difficulty of epidemic prevention and control.

ObjectiveTo explore the therapeutic mechanism of Faeces Bombycis on diabetic gastroparesis （DGP） rats based on phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein （PI3K/Akt/mTOR） signaling pathway. MethodDGP rat model was prepared by random selection of 15 out of 105 rats as blank group. The rats successfully constructed were randomly divided into model group， high-，medium- and low- dose groups （3.2， 1.6， 0.8 g·kg^-1） and moxapride group （1.5 mg·kg^-1）， with 12 rats in each group， and were given gavage for 4 weeks. The gastric emptying rate and random blood glucose were measured. The morphological changes of gastric antrum were observed by hematoxylin-eosin （HE） staining， and the expression of the c-Kit gene was analyzed by immunohistochemistry. The apoptosis of Cajal interstitial cells was observed by in situ end labeling （TUNEL） staining， and the protein expressions of PI3K， phosphorylation（p）-PI3K， Akt， p-Akt， mTOR， and p-mTOR were detected by Western blot. ResultCompared with the blank group， the gastric emptying rate of the model group decreased significantly （P<0.01）， and the glandular structure of the gastric antrum was destroyed. The expression of c-Kit decreased （P<0.01）， and the apoptosis of Cajal interstitial cells （ICC） increased. Compared with the model group， the gastric emptying rate in the high， middle， and low-dose groups of Faeces Bombycis extract and mosapride group increased significantly （P<0.01）. The glandular structure of the gastric antrum became closer， and the apoptosis of ICC decreased. The expression of c-Kit in the high dose group of Faeces Bombycis extract increased significantly. After Western blot testing， compared with the blank group， the protein expression of p-Akt/Akt， p-PI3K/PI3K， and p-mTOR/mTOR in the model group increased. Compared with the model group， the protein expression of p-Akt/Akt in the high dose group of Faeces Bombycis extract decreased （P<0.01）， and the protein expression of p-PI3K/PI3K decreased in the middle and low dose groups of Faeces Bombycis extract and mosapride group decreased （P<0.05， P<0.01）. The protein expression of p-mTOR/mTOR decreased in the low dose group of Faeces Bombycis extract （P<0.05）. In terms of random blood glucose， compared with the blank group， the random blood glucose in the model group increased significantly （P<0.01）， and compared with the model group， the random blood glucose in the high and middle dose groups of Faeces Bombycis extract decreased significantly （P<0.05）. Compared with mosapride group， the protein expression of p-Akt/Akt decreased in the high dose group of Faeces Bombycis extract （P<0.05）， and the protein expression of p-PI3K/PI3K increased in the high， middle， and low dose groups of Faeces Bombycis extract （P<0.05， P<0.01）. ConclusionFaeces Bombycis extract can increase gastric emptying rate， reduce ICC apoptosis， and lower random blood glucose in DGP rats. The high dose group of Faeces Bombycis extract has a significant effect on inhibiting ICC apoptosis， and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:A microsurgical simulation training device based on real clinical scenes was designed and its effectiveness was tested.Methods:From January 1, 2020 to January 1, 2023, postgraduate students in the Plastic and Reconstructive Surgery Department of the First Medical Center of PLA General Hospital and the Plastic Surgery Hospital of Chinese Academy of Medical Sciences were enrolled in this prospective study. The simulation training device consists of four parts: (1)Blood perfusion system, which is used to simulate living animal blood vessels.(2)The inner baffling rod system, which is used to simulate the operation in deep cavity.(3) The exterior baffling rod system, which is used to simulate the operation in difficult positions.(4) A pulsating platform system is used to simulate microsurgery under the influence of respiratory movement. Preliminary verification of the effect of the simulated training device was as follows: Surgeons with no experience in microsurgery were completely randomized assigned to the control group (traditional microsurgery training group) and the experimental group (training group using the simulated training device). After 4 weeks of microsurgical training, the trainees were assigned to perform two surgical skill assessments, the first using a live animal model for end-to-end anastomosis of rat tail arteries, and the second assessment using end-to-end anastomosis of free latissimus dorsi flap arteries in a real case. The performance of the two groups was compared by using operation time and microsurgical GRS score scale including four items of dexterity, visuospatial ability, operative flow and judgment. Chi-squared test was used to analyze gender between the two groups. GRS scores between the two groups were compared by the Mann-Whitney U test. Participants’ ageand operation time between the two groups was compared by independent t-test. P<0.05 was considered statistically significant. Results:A total of 18 trainees were enrolled, including 10 in the control group, 6 males and 4 females, with an average age of (27.80±1.87) years. There were 8 subjects in the experimental group, 4 males and 4 females, with an average age of (28.10±1.56) years old. There were no significant differences in age, gender and other baseline characteristics between the two groups ( P>0.05). There was no significant difference in GRS score and operation time between the control group and the experimental group ( P> 0.05) in the first assessment. However, in the second assessment of real cases, the GRS score of the experimental group was significantly higher than that of the control group(14.25 vs. 5.70), and the operation duration of the experimental group was also shorter than that of the control group, and the difference was statistically significant[(100.37±24.65 ) min vs. (105.60±22.84) min] ( P<0.05). Conclusion:Compared with traditional microsurgery training methods, using microsurgery training devices based on clinical real scenes can effectively shorten the learning curve and enable trainees to master complex micromanipulation skills more quickly.

Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Abstract OBJECTIVE To establish a detection method for fingerprints and content determination of free sugar and hydrolyzed monosaccharide of intracellular glycopeptides in Coriolus versicolor. METHODS PMP derivatization after ultrasonic extraction with water as solvent was determined for free sugars, and PMP derivatization after acid hydrolysis was determined for hydrolyzed monosaccharides. The free sugars and hydrolyzed monosaccharides of raw materials and intermediates of intracellular glycopeptides from different manufacturers were analyzed by HPLC qualitatively and quantitatively. The fingerprints were analyzed by chemometrics analysis, and the differences between intracellular glycopeptides produced by different manufacturers were discussed. RESULTS Both two methods were validated by methodology. The samples from different manufacturers were clustered separately, and three free sugars and two hydrolyzed monosaccharides contributed greatly to the quality difference of intracellular glycopeptides of Coriolus versicolor. CONCLUSION The established analytical method can be effectively used for the determination of free sugars and hydrolyzed monosaccharides in the intracellular glycopeptide of Coriolus versicolor and the study of fingerprints. The adopted chemometrics research method provides guidance for the quality control of the intracellular glycopeptide of Coriolus versicolor.

Objective:To compare the adjuvant chemotherapy project and survival prognosis of patients with stage Ⅱ/Ⅲ colon cancer in different age groups.Methods:In this retrospective study, the clinical data of 770 colon cancer patients undergoing radical resection were collected in the First Affiliated Hospital of Soochow University from Jan 2013 to Dec 2017. Patients were categorized into 3 groups based on age at onset of colon cancer: young group (18-49 years old, 112 cases), middle-aged group (50-64 years old, 351 cases) and older group (65-75 years old, 307 cases).Results:The young group had fewer complications, and the probability of cancer deposit, vascular tumor thrombus and nerve invasion was lower than the middle-aged and older group (12.5% vs. 15.4% vs. 14.3%; 7.1% vs. 9.4% vs. 8.5%; 2.7% vs .8.8% vs. 5.5%), but the probability of signet-ring cell carcinoma and mucinous adenocarcinoma was higher (5.4% vs. 1.4% vs. 1.6%; 14.3% vs. 11.4% vs. 13.4%), the proportion of patients with stage Ⅲ was greater (49.1% vs. 45.0% vs. 47.2%), and they were more willing to receive postoperative chemotherapy (83.9% vs. 81.8% vs. 60.3%). Among patients with stage Ⅱ and Ⅲ colon cancer, the young group and the middle-aged group were 3-4 times more likely to receive adjuvant chemotherapy than the elderly group [ OR=4.153 (95% CI:1.964-8.785), 2.906 (95% CI:1.845-4.579), 3.120 (95% CI:1.310-7.429), 3.588 (95% CI: 1.964-6.556)]. Of those patients who received chemotherapy, young and middle-aged patients had a higher percentage of multiagent regimen use than older patients [ OR=2.050 (95% CI:0.937-4.488), 2.750 (95% CI:1.536-4.923)]. Among patients treated with surgery alone, no significant differences were observed in survival among age groups. Among patients who received surgery and adjuvant chemotherapy, a significantly better survival was observed for young and middle-aged patients with stage Ⅲ [ HR=0.284 (95% CI:0.127-0.632), 0.521 (95% CI:0.333-0.816)] than their older counterparts. Conclusions:Among patients with stage Ⅱ/Ⅲ colon cancer, young and middle-aged patients are more likely to undergo adjuvant chemotherapy and use more radical chemotherapy regimen. Young and middle-aged patients with stage Ⅱ colon cancer had overuse of chemotherapy, but did not result in expected survival improvement.