OBJECTIVES: To study the value of functional echocardiographic parameters in predicting refractory septic shock in neonates. METHODS: A total of 72 neonates with septic shock were enrolled. According to the highest value of septic shock score, they were divided into two groups: refractory (n=30) and non-refractory (n=42). The two groups were compared in terms of clinical data, laboratory findings, and functional echocardiographic parameters. The receiver operating characteristic (ROC) curve was used to evaluate the performance of functional echocardiographic parameters in predicting refractory septic shock. RESULTS: Compared with the non-refractory group, the refractory group had significantly lower cardiac output and cardiac index (CI) and a significantly higher mean arterial pressure (MAP)/CI ratio (P<0.05). CI had a cut-off value of 2.6 L/(min·m²), a sensitivity of 79%, a specificity of 83%, and an area under the ROC curve (AUC) of 0.841 in predicting septic shock-related death (P<0.05), and MAP/CI ratio had a cut-off value of 11.4, a sensitivity of 83%, a specificity of 73%, and an AUC of 0.769 (P<0.05). CI had a cut-off value of 2.9 L/(min·m²), a sensitivity of 69%, a specificity of 69%, and an AUC of 0.717 in predicting all-cause death within 28 days (P<0.05). CONCLUSIONS CI and MAP/CI ratio can be useful for early prediction of septic shock-related death in neonates.
Infant, Newborn ; Humans ; Shock, Septic/diagnostic imaging* ; Echocardiography ; ROC Curve

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ²=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ²=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ²=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ²=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.
Child ; Female ; Male ; Humans ; Hodgkin Disease ; Retrospective Studies ; Neoplasm Recurrence, Local ; China ; Antineoplastic Combined Chemotherapy Protocols ; Prognosis ; Disease-Free Survival

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

Objective: To explore the application effects of feedforward control theory in the rollover bed treatment of mass patients with burn-explosion combined injury. Methods: A retrospective observational research was conducted. From June 13 to 14, 2020, 15 patients with severe burn-explosion combined injury caused by liquefied natural gas tank car explosion and conforming to the inclusion criteria were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 13 males and 2 females, aged 33-92 (66±17) years. All the patients were treated with rollover bed from 48 h post admission, and the feedforward control theory was introduced, including establishing a special feedforward control management team for rollover bed, clarifying the duties of the medical staff in the rollover bed treatment of patients, implementing the cooperation strategy of multidisciplinary physician, training and examining for 80 nurses in the temporarily organized nurse team in the form of "rollover bed workshop", and formulating the checklist and valuation list of rollover bed treatment for continuous quality control. The frequency and the total number of turning over, and successful rate of one-time posture change with the rollover bed of patients within 30 days of admission were recorded, the occurrences of adverse events caused by improper operation for the rollover bed during the treatment were observed, including respiratory and cardiac arrests, treatment interruption, unplanned extubation, bed falling, and skin graft displacement. The lowest levels of arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), the number of patients with oxygenation index>300 mmHg (1 mmHg=0.133 kPa), and the occurrence of acute respiratory distress syndrome (ARDS) of patients within 2 days of admission and on the 30^th day of admission were recorded. Results: Within 30 days of admission, the patients were turned over with the rollover bed for 2 to 6 times each day, with a total of 1 320 turning over operations, the successful rate of one-time posture change reached 99.9% (1 319/1 320), and no adverse event occurred. Within 2 days of admission, the lowest levels of PaO₂ and PaCO₂ of the patients were (100±19) and (42±4) mmHg, respectively, and the number of patients with mild, moderate, and severe ARDS were 10, 2, and 3, respectively, and none of the patients had oxygenation index>300 mmHg. On the 30^th day of admission, the lowest levels of PaO₂ and PaCO₂ of the patients were (135±28) and (37±8) mmHg, respectively, 3 patients developed moderate ARDS, 1 patient developed severe ARDS, and 11 patients had oxygenation index>300 mmHg. Conclusions: The introduction of feedforward control theory in the treatment of rollover bed of mass patients with burn-explosion combined injury can ensure safe and successful completion of turning over with the rollover bed, promote the repair of burn wound, and improve respiratory function, and therefore improve the treatment quality of patients.
Blood Gas Analysis ; Burns/therapy* ; Explosions ; Female ; Humans ; Male ; Respiratory Distress Syndrome ; Retrospective Studies

Aim To explore the anti-inflammatory effect of taurolithocholic acid (TLCA) through network pharmacology-based analyses, to verify with in vitro macrophage study and to reveal the possible mechanisms. Methods The potential targets of TLCA were acquired from public database, and then the protein-protein interaction (PPI) networks against inflammation were constructed and visualized by using Cytoscape. Gene ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. The binding activity of TLCA and its target (TGR5) was evaluated through molecular docking analysis. Lastly, the results of the network analysis were confirmed by lipopolysaccharide and interferon-γ induced RAW264.7 cells. Results There were 87 anti-inflammatory potential targets were screened. GO analysis revealed gene functions were mainly involved in regulation of inflammatory response, membrane raft and protein tyrosine kinase. The results of KEGG pathway analysis suggested that PI3K-Akt signaling pathway, human cytomegalovirus infection might be the critical pathways of TLCA against inflammation. The results of in vitro experiments showed that TLCA decreased the LPS and IFN-γ induced inflammatory response in RAW 264.7 macrophages. Furthermore, the expression of TGR5 protein increased after TLCA treatment. Conclusions The potential therapeutic targets of TLCA against inflammation are revealed through network pharmacology analysis. Our results indicate that TLCA might regulate key inflammatory markers through the membrane receptor TGR5.

Background: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. Methods: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. Results: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) Conclusions: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. Clinical trial registration NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)， the male SD rats were intraperitoneally injected with streptozotocin(STZ， 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)， the low-dose Nar group(Nar25)， the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25， Nar50， Nar100 groups were orally administered with Nar at the doses of 25.0， 50.0， 100.0 mg·kg⁻¹ per day， respectively， while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment， fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)， C/EBP homologous protein(CHOP)， cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results， compared with control group， the myocardial structure was damaged， the content of MDA was increased， while the activities of SOD were decreased(<0.05) in T1DR group. GRP78， CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(<0.05， <0.01). Compared with T1DR group， myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased， while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). After treatment with Nar for 8 weeks， myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased， while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.
Animals ; Apoptosis ; Cardiotonic Agents ; pharmacology ; Caspase 12 ; metabolism ; Diabetes Mellitus, Experimental ; Diabetic Cardiomyopathies ; drug therapy ; Endoplasmic Reticulum Stress ; drug effects ; Flavanones ; pharmacology ; Heat-Shock Proteins ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Transcription Factor CHOP ; metabolism

ObjectiveTo explore Mycoplasma genitalium (MG) infection in the urogenital tract of infertile men and its influence on semen quality.

METHODSSemen samples were collected from 352 infertile males in the Center of Reproductive Medicine of Nanjing General Hospital from March to July 2015. MG infection was detected by real-time fluorescence simultaneous amplification and testing and semen analyses were conducted according to the WHO Laboratory Manual for the Examination and Processing of Human Semen (5th Ed) on the semen pH value, semen volume, total sperm count, sperm concentration, total sperm motility, percentages of progressively motile sperm (PMS) and immotile sperm (IMS), and sperm DNA fragmentation index (DFI). The data obtained were subjected to statistical analysis by t-test and non-parametric test (Wilcoxon test).

RESULTSMG infection was found in 3.4% (12/352) of the infertile patients. Compared with the MG-positive cases, the MG-negative ones showed a significantly higher semen volume (［2.85 ± 0.14］ vs ［3.84 ± 0.12］ ml, P = 0.008) and percentage of PMS (［15.86±1.72］ vs ［60.95 ± 5.63］ %, P = 0.032) but a lower DFI (［30.73 ±2.24］ vs ［20.71 ± 1.55］%, P = 0.014). However, no statistically significant differences were observed between the two groups in the semen pH value (7.38 ±0.02 vs 7.39 ± 0.01, P = 0.774), sperm concentration (［52.96 ± 15.78］ vs ［60.05 ± 4.29］×10⁶/ml, P = 0.683), sperm count (［154.15 ± 46.37］ vs ［221.56 ± 15.43］×106, P = 0.236), total sperm motility (［29.04 ± 3.11］ vs ［33.52 ± 1.51］ %, P = 0.626), or percentage of IMS (［23.57 ± 0.99］ vs ［62.34 ± 1.69］ %, P = 0.691).

CONCLUSIONSUrogenital MG infection is common in infertile males and potentially affects the semen quality, especially sperm vitality of the patient.

DNA Fragmentation ; Humans ; Infertility, Male ; microbiology ; physiopathology ; Male ; Male Urogenital Diseases ; microbiology ; Mycoplasma Infections ; complications ; Mycoplasma genitalium ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; physiology

BACKGROUND: Previous studies have found that electroacupuncture (EA) could effectively inhibit the expression of p38 and Fas mRNA mediated by MAPK signaling pathways, to further inhibit the apoptosis of chondrocytes. Meanwhile,EA delays the degeneration of articular cartilage mediated by JAK-STAT signaling pathway through upregulating the expression levels of transforming growth factor β1 as well as the mRNA expression levels of STAT3, Smad3 and LepR.OBJECTIVE: To explore the effect of EA on the cartilage ultrastructure and mRNA expression levels of Ras, Raf,MEK1/2 and ERK1/2 in the rat with knee osteoarthritis.METHODS: The rat models of knee osteoarthritis were established, and randomized into four groups at 2 weeks after modeling: model group received no interventions; 15- and 30-minute EA groups were given EA at the Hsiyen (medical,extra) of bilateral knee joints for 15 and 30 minutes, respectively; PD98059 group was given the intravenous injection of extracellular signal-regulated kinase inhibitor PD98059. The intervention time was 3 months. Those rats received normal feeding served as blank control group.RESULTS AND CONCLUSION: Transmission electron microscopy showed that compared with the model group, the chondrocytes in the 15- and 30-minute EA and PD98059 groups changed little, the nucleus was larger, partial endoplasmic reticulum cisterna expanded, and the mitochondria structure was clear. ELISA results showed that the 15-and 30-minute EA and PD98059 groups had a significant decrease in the level of tumor necrosis factor α compared with the model group (P < 0.01). RT-PCR revealed that the mRNA expression levels of Ras, Raf, MEK1/2 and ERK1/2 in the 15- and 30-minute EA and PD98059 groups were significantly downregulated (P < 0.05 or P < 0.01). These results indicate that EA can alleviate chondrocyte injury in the rat osteoarthritic model, reduce the level of tumor necrosis factor α in the synovium, and downregulated the expression levels of Ras, Raf, MEK1/2 and ERK1/2 mRNA, further delaying the chondrocyte degeneration in osteoarthritis.

Bartonella species can infect a variety of mammalian hosts and cause a broad spectrum of diseases in humans, but there have been no reports of Bartonella infection in Ochotonidae. This is the first study to detect Bartonella in plateau pikas in the Qinghai plateau, providing baseline data for the risk assessment of human Bartonella infection in this area. We obtained 15 Bartonella strains from 79 pikas in Binggou and Maixiu areas of Qinghai with a positive rate of 18.99%. Based on the phylogenetic analysis of the Bartonella citrate synthase (gltA) gene sequences, most strains were closely related to B. taylorii (3/15) and B. grahamii (12/15). The latter is a pathogenic strain in humans. Our results suggest that a corresponding prevention and control strategy should be taken into consideration in the Qinghai province.
Animals ; Bartonella ; classification ; genetics ; isolation & purification ; Bartonella Infections ; epidemiology ; microbiology ; transmission ; veterinary ; China ; epidemiology ; Female ; Genotype ; Humans ; Lagomorpha ; Male ; Phylogeny