A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

With the widespread use of carbapenem antibiotics,the clinical detection rate of carbapenem-resistant Gram-negative bacilli has shown a significant increase.Carbapenem-resistant Gram-negative bacilli isolates are often extensively or fully resistant,resulting in limited antimicrobial treatment options and high morbidity and mortality rates,posing a serious public health threat.The clinical treatment of carbapenem-resistant Gram-negative bacilli includes the use of single or combination antimicrobials such as polymyxin,tigecycline,and fosfomycin.A number of new antimicrobials and therapeutic approaches are under development.The clinical management of carbapenem-resistant Gram-negative infections is severely challenged by the limited choice of antimicrobial agents.Therefore,this article reviews the current status and progress of antimicrobial treatment for carbapenem-resistant Gram-negative bacilli to providing clinical reference.

Objective To investigate the efficacy of flupentixol combined with ondansetron in preventing postoperative nausea and vomiting(PONV)in patients receiving sufentanil and dezocine patient-controlled intravenous analgesia(PCIA).Methods Surgical patients receiving sufentanil and dezocine PCIA were randomly divided into treatment and control groups using a random number table.The control group received sufentanil 150 μg,dezocine 20 mg,and ondansetron 8 mg for PCIA,while the treatment group received sufentanil 150 μg,dezocine 20 mg,flupentixol 5 mg,and ondansetron 8 mg for PCIA.The incidence of PONV,severity of PONV,heart rate(HR),mean arterial pressure(MAP),blood oxygen saturation(SPO2)levels at different time points after surgery,surgery-related indicators,visual analogue scale(VAS)scores,Ramsay scores,PCIA pressing times,and incidence of adverse drug reactions were compared between the two groups.Results The incidence of PONV in the treatment group and the control group at 2,12,24,36 and 48 hours after surgery were 1.64％,4.84％,6.56％,3.28％,0 and 14.75％,18.03％,19.67％,16.39％,9.84％,respectively.The HR at 24 hours after surgery in the treatment group and the control group were(91.42±8.75)and(98.13±9.62)beat·min-1,respectively;the MAP were(91.98±4.56)and(99.05±4.17)mmHg;SPO2 were(98.13±1.65)％and(98.95±1.82)％;VAS scores were 2.68±0.49 and 2.97±0.63;Ramsay scores were 2.27±0.65 and 2.05±0.32;PCIA pressing times were(2.14±0.37)and(4.36±0.78)times,respectively.The differences in the above indicators between the treatment group and the control group were statistically significant(all P＜0.05).The incidence of total adverse drug reactions after surgery in the treatment group and the control group were 13.12％and 8.20％,respectively,with no statistically significant difference(P＞0.05).Conclusion Flupentixol combined with ondansetron can reduce the risk of PONV caused by sufentanil combined with dezocine PCIA after surgery,ensuring good analgesic effects and safety.

Viral myocarditis(VMC)is the leading cause of dilated cardiomyopathy,which can lead to heart failure and sudden cardiac death.With the development of high-throughput sequencing technology,non-coding RNA(ncRNA)plays an important role in the occurrence and development of VMC.ncRNA promotes the occurrence and development of VMC by regulating viral replication,immune cell function,myocardial cell death,myocardial interstitial fibrosis,and other pathological processes.This article reviews the research progress of ncRNA in VMC and provides new ideas for the pathogenesis,diagnosis,and treatment of VMC.

Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg-1)at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9％NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL-1;the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL-1;the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL-1;cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL-1;TXA2 content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL-1;PGI2 content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL-1;the relative expression levels of Notch1 protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1 protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P＜0.01,P＜0.001).Conclusion Lepirudine can inhibit thrombin activation in the treatment of acute pulmonary embolism by activating the Notch signaling pathway.

Objective:To explore the potential causal relationship between gut microbiota and teratozoospermia.Methods:We searched the database of Genome-Wide Association Study(GWAS)for gut microbiota-and teratozoospermia-related data.We used gut microbiota as an exposure factor,determined the instrumental variables according to the GWAS data on 18 340 participants released by the MiBioGen Alliance,and derived the outcome variables from the European data on teratozoospermia,with a sample size of 85 716,including 915 cases and 209 006 controls.Using inverse-variance weighting(IVW),MR-Egger regression and the weighted median estimator(WME),we performed two-sample Mendelian randomization(MR)analysis on the retrieved data,and estimated the causal relationship between gut microbiota and teratozoospermia based on the β value.Results:Two-sample MR analysis indicated that the class Erysipelotrichia,family Erysipelotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridialesm and order Erysipelotrichales were causally related with the increased risk,while the family Porphyromonadaceae with the decreased risk of teratozoospermia.Conclusion:The class Erysipelotrichia,family Erysipe-lotrichaceae,family Streptococcaceae,genus Coprococcusl,genus Ruminococcaceae UCG009,genus Streptococcus,order Clostridia-lesm and order Erysipelotrichales are one of the causes of teratozoospermia,related to the increased risk of the condition,while the family Porphyromonadaceae has a protective effect on sperm morphology,reducing the risk of teratozoospermia.