[The investigation on the acute, severe hepatitis of unknown origin in children]. / å„¿ç«¥ä¸æ˜ŽåŽŸå› æ€¥æ€§ä¸¥é‡è‚ç‚Žç— ä¾‹è°ƒæŸ¥è¿›å±•.

In April 2022, the United Kingdom notified the World Health Organization (WHO) of an unexpected increase of acute hepatitis of unknown origin in children. Subsequent investigations have found more than 400 cases in more than 20 countries and regions around the world. Although the potential role of adenovirus type 41 in the pathogenesis of these cases is one hypothesis, but it is probably not the only pathogenic factor, and other infectious and non-infectious causes cannot be completely ruled out. For hepatitis caused by non-hepatitis A, B, C, D and E viruses, there is a lack of systematic monitoring and research, and many unknowns still exist. According to the current etiology speculation and epidemiological characteristics of adenovirus in China, cases of acute hepatitis with unknown origin may be found in China in the future. There is also a risk of imported cases. This article systematically sorts out the reports and studies on child acute hepatitis of unknown origin, hoping to attract the attention of pediatric clinicians in China, raise awareness and vigilance, and calmly prepare for possible abnormal situations.

New Mg2+/Ge4+-Stabilized Gd3MgxGexAl5-2xO12:Ce Garnet Phosphor with Orange-Yellow Emission for Warm-White LEDs (x = 2.0-2.5).

By stabilization of the Gd3Al5O12 garnet by replacing 80% or more of Al3+ with Mg2+/Ge4+ pairs, a series of new orange-yellow-emitting Gd3MgxGexAl5-2xO12:Ce (x = 2.0-2.5) phosphors were successfully developed for potential application in warm-white-light-emitting diodes (WLEDs). Rietveld structure refinement proved that Mg2+ first substitutes the octahedral Al3+ ion, followed by the replacement of the tetrahedral Al3+ together with Ge4+. The band structure of the x = 2.0 typical garnet was analyzed via density functional theory (DFT) calculations. The incorporation of an increasing content of Mg2+/Ge4+ was experimentally shown to narrow the band gap and expand the unit cell of the garnet host and blue shift the emission/excitation wavelength and shorten the fluorescence lifetime of Ce3+. The photoluminescence behaviors were rationalized by considering the influence of Mg2+/Ge4+ on the crystal structure, band structure, and local coordination. An LED lamp fabricated by combining the (Gd2.97Ce0.03)Mg2Ge2AlO12 optimal phosphor with a 450 nm-emitting InGaN blue LED chip exhibited a color-rendering index of 71.6, luminous efficacy of 16.1 lm/W, and a low correlated color temperature of 2201 K under a driving current of 20 mA, indicating that phosphor may have potential application in warm WLEDs.

Acylphloroglucinol trimers from Callistemon salignus seeds: Isolation, configurational assignment, hAChE inhibitory effects, and molecular docking studies.

Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC50 values of 1.22 ±â€¯0.23, 2.28 ±â€¯0.19, and 4.96 ±â€¯0.39 µM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 µM, respectively.

New Cytotoxic Cytochalasans from a Plant-Associated Fungus Chaetomium globosum kz-19.

Four new cytochalasans, phychaetoglobins A-D (1-4), together with twelve known cytochalasans (5-16), were isolated from a mangrove-associated fungus Chaetomium globosum kz-19. The new structures were elucidated on the basis of extensive 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculations. The absolute configuration of 2 was established by application of Mosher's method. Compounds 4-8 exhibited moderate cytotoxicities against A549 and HeLa cell lines with the IC50 values less than 20 µM.

The Safety and Efficacy of Apatinib Treatment in Addition to Concurrent Chemoradiotherapy in Patients with Nonoperative Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND Esophageal cancer is a common gastrointestinal malignancy in China. We evaluated the efficacy and safety of adding Apatinib to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. MATERIAL AND METHODS In this single-center retrospective study, we compared short-term efficacy, long-term efficacy, and adverse events between patients who received Apatinib and concurrent chemoradiotherapy (Apatinib group), and those who received only concurrent chemoradiotherapy (CCRT group). RESULTS Sixty-five patients with stage II and III esophageal squamous cell carcinoma were enrolled (31 in the Apatinib group, 34 in the CCRT group). After treatment, the therapy response rate (the sum of the complete and partial remission rates) was significantly higher in the Apatinib group than in the CCRT group (P=0.045); the complete remission rate was particularly higher in the Apatinib group. Median progression-free survival in the Apatinib group (12 months) was higher than that of the CCRT group (7 months), and the 1- and 2-year progression-free survival rates were significantly higher in the Apatinib group than in the CCRT group (47.0% vs. 30.3% and 20.2% vs. 12.1%, respectively; P=0.040). The main adverse effects of Apatinib treatment were elevated blood pressure, proteinuria, hand-foot syndrome, fatigue, and oral mucositis, all of which were level 1-2. Cox multivariate regression analysis indicated T stage and short-term efficacy were independent prognostic factors for overall and progression-free survival. CONCLUSIONS For patients with locally advanced esophageal squamous cell carcinoma, combining Apatinib with concurrent chemoradiotherapy can improve patient survival and significantly prolong progression-free survival, with tolerable adverse reactions.

Widespread of non-typeable Haemophilus influenzae with high genetic diversity after two decades use of Hib vaccine in China.

BACKGROUND: The aim of this study was to analyze the microbiological characteristics of nasopharyngeal carriage Haemophilus influenzae isolates collected from children with respiratory infections in Beijing hospital and Youyang Hospital of China. METHODS: The serotypes of all isolates were determined using latex agglutinated antisera (a-f). The minimum inhibitory concentrations (MICs) of 11 antibiotics were determined using E-test strips. For the beta-lactamase-negative ampicillin-resistant (BLNAR) isolates, ftsI gene was sequenced based on fragments amplified by PCR. STs of H influenzae isolates were determined by multi-locus sequence typing. RESULTS: The overall carriage rate of H influenzae in the study population was 9.1% (362/3984). One hundred and ninety H influenzae isolates which were selected in our study were non-typeable (NTHi) and 44 (23.2%) of them were positive for ß-lactamase. All isolates were susceptible to ceftriaxone and levofloxacin. Susceptibility rates to erythromycin and sulfamethoxazole-trimethoprim in Beijing were significantly higher than Youyang (P < .05). Thirty-six BLNAR isolates were identified. The MLST analysis showed 108 STs in 190 isolates, the most common of which were ST408 (11, 5.8%), ST914 (10, 5.3%), ST57 (9, 4.7%), and ST834 (6, 3.2%). Twelve STs were detected in both of the study sites, which covered 63 isolates. CONCLUSIONS: All isolates in the present study were NTHi, which suggested widespread of this type in China. The BLNAR isolates were detected more frequently than before. Because high genetic diversity of NTHi isolates of H influenzae exists worldwide, it is important to continuously monitor these bacteria in the future.

High Prevalence of Macrolide-Resistant Bordetella pertussis and ptxP1 Genotype, Mainland China, 2014-2016.

According to the government of China, reported cases of pertussis have increased remarkably and are still increasing. To determine the genetic relatedness of Bordetella pertussis strains, we compared multilocus variable-number tandem-repeat analysis (MLVA) results for isolates from China with those from Western countries. Among 335 isolates from China, the most common virulence-associated genotype was ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3A/tcfA2, which was more frequent among isolates from northern than southern China. Isolates of this genotype were highly resistant to erythromycin. We identified 36 ptxP3 strains mainly harboring ptxA1 and prn2 (35/36); ptxP3 strains were sensitive to erythromycin and were less frequently from northern China. For all isolates, the sulfamethoxazole/trimethoprim MIC was low, indicating that this drug should be recommended for patients infected with erythromycin-resistant B. pertussis. MLVA of 150 clinical isolates identified 13 MLVA types, including 3 predominant types. Our results show that isolates circulating in China differ from those in Western countries.

The maternal antibody against diphtheria, tetanus and pertussis showed distinct regional difference in China.

BACKGROUND: Passive transferred antibodies to the fetus play an essential role on protecting neonates and young infants until infant vaccination is more efficacious. However, very little is known about the discrepancy of DTP vaccine associated antibodies level in neonates from different economic areas in China. METHODS: In 2018, 200 neonates hospitalized in Shunyi Women and Children's Hospital in Beijing, and 238 neonates hospitalized in Qianjiang Central Hospital located in the southwestern mountainous areas were included in this study. Antibodies specific for the antigens covered by DTP vaccine were determined using ELISA Kits (Euroimmun, Lübeck, Germany). The cut off value of ≥0.1 IU/ml (anti-diphtheria, anti-Dtx), > 0.1 IU/ml (anti-tetanus, anti-Ttx) and > 40 IU/ml (anti-pertussis toxin, anti-Ptx) were used to assess the percentage of protected neonates, respectively. RESULTS: The antibody levels in the neonates from Qianjiang (0.04 IU/ml for anti-Dtx IgG and 0.07 IU/ml for anti-Ttx IgG) were significantly lower than those from Shunyi (0.12 IU/ml for anti-Dtx IgG and 0.18 IU/ml for anti-Ttx IgG). The prevalence of protective anti-Dtx and anti-Ttx IgG were lower in the neonates from Qianjiang (7.1% for anti-Dtx IgG and 7.6% for anti-Ttx IgG) than in those from Shunyi (30.5% for anti-Dtx and 38.5% for anti-Ttx). The neonates from Qianjiang also had lower detectable rate of anti-Dtx (57.5%) and anti-Ttx IgG (55.8%) than neonates from Shunyi (97.5% for anti-Dtx and 71.0% for anti-Ttx). However, the detectable rate of anti-Ptx IgG in neonates from Qianjiang (39.9%) was higher significantly than in those from Shunyi (30.5%). Two neonates from Qianjiang have anti-PT IgG ≥100.0 IU/ml, which suggested that their mothers have a recent pertussis course. CONCLUSIONS: The regional discrepancy of the protective antibody rates might be caused by different vaccine coverage and pertussis exposure, which suggested the importance of Tdap booster immunization for pregnant women or women at childbearing age, those living undeveloped areas in particular.

Cytotoxic Withanolides from the Whole Herb of Physalis angulata L.

Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (1-2), together with six known analogues (3-8), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis.

[Antimicrobial susceptibility and antigen genotypes of Bordetella pertussis strains isolated from neonates].

OBJECTIVE: To investigate the alternative antimicrobial drugs for the treatment of neonatal pertussis and the antigen genotypes of Bordetella pertussis (B. pertussis) strains. METHODS: A total of 32 B. pertussis strains isolated from neonates between May 2013 and July 2018 were used in this study. E-test stripes were used to measure the minimal inhibitory concentration (MIC) of 18 antimicrobial drugs including erythromycin, sulfamethoxazole-trimethoprim (SMZ) and ampicillin. The 23S rRNA gene of isolated strains was amplified and sequenced to identify the mutation site of erythromycin resistance gene, and the seven antigen genotypes of B. pertussis strains (ptxA, ptxC, ptxP, prn, fim2, fim3 and tcfA2) were analyzed. RESULTS: Of the 32 B. pertussis strains, 25 (78%) were resistant to erythromycin, azithromycin, clarithromycin and clindamycin, with an MIC of >256 mg/L, and A2047G mutation was observed in the 23S rRNA gene. All strains had an MIC of ≤0.064 mg/L for SMZ. The MIC of ampicillin, amoxicillin, amoxicillin-clavulanic acid and ceftriaxone ranged from 0.032 to 1 mg/L. The strains resistant to macrolide antibiotics had an antigen genotype of ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3-1/tcfA2. CONCLUSIONS: B. pertussis strains from neonates are often resistant to macrolides, and the in vitro test shows that off-label use of sulfonamides is a reliable regimen for the treatment of neonates with macrolide-resistant pertussis. The prevalence of drug-resistant strains further emphasizes the importance of immunoprophylaxis.

Rubella seroprevalence among pregnant women in Beijing, China.

BACKGROUND: Rubella infection in pregnant women can result in serious effects, such as miscarriages, stillbirths, and congenital rubella syndrome (CRS). However, very little is known about the rubella seroprevalence among pregnant women in China. METHODS: This is a cross-sectional and hospital-based study. From June 2016 through March 2017, a total of 324 serum samples from healthy pregnant women were collected in the Shunyi Women and Children's Hospital of Beijing Children's Hospital. Rubella-specific IgG antibody was determined by ELISA (Euroimmun, Lübeck, Germany) kits. International assigned cut-off values of ≥10 IU/ml were used to assess the percentage of pregnant women with protective IgG concentrations. RESULTS: The total rate of protected individuals was 83.3% (95% CI: 78.9%-87.0%). The protective rates of pregnant women in 17-26 years group, 27-36 years group and 37-46 years group were 84.0% (95% CI: 75.3%-90.1%), 81.9% (95% CI: 74.9%-87.4%) and 84.9% (95% CI: 75.8%-90.9%) respectively. No significant difference in protective rates among the three age groups was found (P = 0.83). There were also no statistically significant correlations between protective rates and gravidity (P = 0.84), parity (P = 0.84), birth place (P = 0.16), residence area (P = 0.58), education (P = 0.40) or occupation (P = 0.65). CONCLUSIONS: Despite the generally low vaccination coverage for rubella, most of Chinese pregnant women had potent rubella immunity. However, at least 16.7% of pregnant women were susceptible to rubella, which suggested rubella immunization in Chinese women at or before child-bearing age.

Seroprevalence of diphtheria and pertussis immunoglobulin G among children with pneumonia in Ji'nan, China.

BACKGROUND: Vaccination is still one of the most important methods to control and prevent childhood infections including diphtheria and pertussis. This study evaluated the level of diphtheria (DT) and pertussis (PT)-related antibodies among children with pneumonia in Ji'nan, China. METHODS: A total of 484 sera of children from 1 day to 13 years of age were collected from 2014 to 2015 in Ji'nan. Children with recent history of pertussis were excluded from this study. Anti-DT and PT IgG concentrations were measured by ELISA (Euroimmun, Lübeck, Germany). RESULTS: Of the 484 subjects tested, the overall positivity rate of anti-DT IgG (≥0.1 IU/ml) was 48.97%, and the highest positivity rate of anti-DT IgG (68.55%) and proportion with long term protection (23.27%) were observed in children aged 6 m- < 3 y. For anti-PT IgG, 334 subjects (69.01%) had anti-PT IgG levels below the lower limit of detection (5 IU/ml). Even with detectable anti-PT antibodies, the majority (115/150, 76.67%) of them had antibody levels of 5- < 40 IU/ml. The highest proportion of subjects with detectable anti-PT IgG (≥5 IU/ml) was observed in children aged < 6 m (44.36%), then the proportion continually decreased to 15.0% at 3 y- < 6 y (χ2 = 24.05, p < 0.0001). The highest positivity rate (≥40 IU/ml) was only 8.27% in children aged < 6 m. Subjects with an anti-PT IgG ≥100 IU/ml were observed in all the groups and there were no significant differences in the proportions of subjects with a level ≥ 100 IU/ml among these age groups (χ2 = 2.572, p = 0.4624). A total of 5 subjects had anti-PT IgG ≥100 IU/ml (≥1 years post pertussis vaccination) which was considered to be indicative of a recent pertussis infection. CONCLUSIONS: We demonstrated low antibody levels and protection against pertussis in our study population. The anti-PT IgG maintained a low level throughout all age groups, and even no immune responses were observed after the basic immunization and booster. Our study supported the need to reevaluate the immune response of DTP vaccine which was used in Shandong province after 2010.

[Secondary metabolites of Streptomyces sp. A1693].

By means of various chromatographic methods such as Sephadex LH-20，ODS，and semi-preparative HPLC，ten compounds were isolated from Streptomyces sp. A1693 and their structures were elucidated on the basis of spectroscopic data and physico-chemical methods. The compounds comprised 5 butenolides，2 diketopiperazines，and 3 antimycin antibiotics. The structures were identified as (5S)-5-(11-hydroxymethyloctyl)furan-2(5H)-one (1), (5S)-5-(11-hydroxy-11-methylheptyl)furan-2(5H)-one (2), (5S)-5-(11-methyl-12-oxooctyl) furan-2(5H)-one (3), (5S)-5-(11-hydroxy-11-methyloctyl)furan-2(5H)-one (4), (5S)-5-(11-hydroxy-12-methyloctyl)furan-2(5H)-one（5），cyclo-Phe-Val (6)，cyclo-Phe-Ile (7)，uranchimycin A (8)，uranchimycin B (9)，and deisovalerylblastomycin (10). Among them，1 was defined as a new compound. All the compounds didn't show the cytotoxic activity against A549 cell line (IC50>50 mg·L⁻¹).

[Efficacy of recombinant human thrombopoietin combined with high-dose dexamethasone in the treatment of refractory immune thrombocytopenia in children].

OBJECTIVE: To explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP). METHODS: Fifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6 mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300 U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment. RESULTS: After 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups. CONCLUSIONS: rhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.

Interferon-γ safeguards blood-brain barrier during experimental autoimmune encephalomyelitis.

The function of blood-brain barrier is often disrupted during the progression of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the molecular mechanism of blood-brain barrier modulation during neuroinflammation remains unclear. Herein, we show that the expression of interferon-γ (IFNγ) receptor on endothelial cells (ECs) protected mice from the brain inflammation during EAE. IFNγ stabilized the integrity of the cerebral endothelium and prevented the infiltration of leukocytes into the brain. Further analysis revealed that IFNγ increased the expression of tight junction proteins zonula occludens protein 1 and occludin, as well as membranous distribution of claudin-5, in brain ECs. Silencing claudin-5 abolished the IFNγ-mediated improvement of EC integrity. Taken together, our results show that IFNγ, a pleiotropic proinflammatory cytokine, stabilizes blood-brain barrier integrity and, therefore, prevents brain inflammation during EAE.

Detection of Bordetella spp. in children with pertussis-like illness from 2018 to 2024 in China.

OBJECTIVE: To evaluate the role of Bordetella pertussis (B. pertussis), B. parapertussis, B. holmesii, and B. bronchiseptica on pertussis resurgence in China, particularly the sharp rise since the latest winter. METHODS: Nasopharyngeal swabs collected from children with pertussis-like illness from January 2018 to March 2024 were cultured to detect B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica, and tested for all of these except for B. bronchiseptica using a pooled real-time polymerase chain reaction (PCR) kit targeting insertion sequences ptxS1, IS481, IS1001, and hIS1001. RESULTS: Out of the collected 7732 nasopharyngeal swabs, 1531 cases tested positive for B. pertussis (19.8%, 1531/7732), and 10 cases were positive for B. parapertussis (0.1%, 10/7732). B. holmesii and B.bronchiseptica were not detected. The number of specimens and the detection rate of B. pertussis were 1709 and 26.9% (459/1709) in 2018, 1936 and 20.7% (400/1936) in 2019, which sharply declined to 308 and 11.4% (35/308) in 2020, 306 and 4.2% (13/306) in 2021, and then notably increased to 754 and 17.6% (133/754) in 2022, 1842 and 16.0% (295/1842) in 2023, 877 and 22.3% (196/877) in the first quarter of 2024. The proportion of children aged 3 to less than 6 years (preschool age) and 6 to 16 years (school age) in pertussis cases increased significantly during the study period, especially the proportion of school-aged children increased from 2.0% (9/459) in 2018 to 40.8% (80/196) in 2024. CONCLUSIONS: B. pertussis was the predominant pathogen among children with pertussis-like illness in China, with sporadic detection of B. parapertussis and no detection of B. holmesii or B.bronchiseptica. The preschool and school-age children are increasingly prevalent in B. pertussis infection cases, which may be associated with the latest rapid escalation of pertussis outbreak.

Seroprevalence of tetanus and pertussis antibodies among health care workers in Wuhu, China.

This study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People's Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20-29 age group, followed by the 30-39 age group (10.57%), 40-49 age group (5.80%), and 50-59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20-39 age group and 40-59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

Adipose tissue-derived mesenchymal stromal cells attenuate acute lung injury induced by trauma and haemorrhagic shock.

BACKGROUND: Mesenchymal stromal cells (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and hemorrhagic shock (THS)-induced ALI. METHODS: ALI model induced by THS was constructed by fractures plus abdominal trauma plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 106 ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated. RESULTS: Administration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1ß, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue. CONCLUSION: Our data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.

Optimal treatment strategy and prognostic analysis for patients with non-metastatic pT4 colon adenocarcinoma.

Objective: This study endeavored to explore the optimal treatment strategy and conduct a prognostic analysis for patients diagnosed with pT4M0 (pathologic stage T4) colon adenocarcinoma (COAD). Methods and materials: A total of 8,843 patients diagnosed with pT4M0 COAD between January 2010 and December 2015 were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into a training set and an internal validation set using a 7:3 ratio. Variables that demonstrated statistical significance (P<0.05) in univariate COX regression analysis or held clinical significance were incorporated into the multivariate COX regression model. Subsequently, this model was utilized to formulate a nomogram. The predictive accuracy and discriminability of the nomogram were assessed using the C-index, area under the curve (AUC), and calibration curves. Decision curve analysis (DCA) was conducted to confirm the clinical validity of the model. Results: In the entire SEER cohort, the 3-year overall survival (OS) rate (74.22% vs. 63.20%, P<0.001) and the 3-year cancer-specific survival (CSS) rate (76.25% vs. 66.98%, P<0.001) in the surgery combined with postoperative adjuvant therapy (S+ADT) group surpassed those in the surgery (S) group. Multivariate COX regression analysis of the training set unveiled correlations between age, race, N stage, serum CEA (carcinoembryonic antigen), differentiation, number of resected lymph nodes, and treatment modalities with OS and CSS. Nomograms for OS and CSS were meticulously crafted based on these variables, achieving C-indexes of 0.692 and 0.690 in the training set, respectively. The robust predictive ability of the nomogram was further affirmed through receiver operating characteristic (ROC) and calibration curves in both the training and validation sets. Conclusion: In individuals diagnosed with pT4M0 COAD, the integration of surgery with adjuvant chemoradiotherapy demonstrated a substantial extension of long-term survival. The nomogram, which incorporated key factors such as age, race, differentiation, N stage, serum CEA level, tumor size, and the number of resected lymph nodes, stood as a dependable tool for predicting OS and CSS rates. This predictive model held promise in aiding clinicians by identifying high-risk patients and facilitating the development of personalized treatment plans.