Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; C-Reactive Protein ; Caspase 3/metabolism* ; Interleukin-10 ; Interleukin-6/metabolism* ; Lactate Dehydrogenases/metabolism* ; Myeloblastin/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Network Pharmacology ; Procalcitonin/therapeutic use* ; Sepsis/genetics* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Objective: To examine the independent and combined effects of pre-pregnancy BMI and gestational diabetes (GDM) on early adiposity rebound (AR) timing in children. Methods: Based on the "Ma'anshan Birth Cohort Study", 2 896 eligible maternal and infant pairs were recruited. In the cohort, we collected pre-pregnancy height, weight, 24 to 28 weeks GDM diagnosis, follow-up at 42 days, three months, six months, nine months of age, and every six months after one year of age, and continuously followed up to 6 years old, and obtained the child's length/height, weight, and other data. The intensity of the association between pre-pregnancy BMI, GDM, and early AR timing was analyzed by the multivariate logistic regression model. Multiplication and additive models were used to analyze how pre-pregnancy BMI and GDM influenced early AR timing in children. Results: The prevalence of underweight, average weight, overweight, and obesity before pregnancy were 23.2% (672), 66.4% (1 923), 8.7% (251), and 1.7% (50). The prevalence of GDM was 12.4%. We found that 39.3% of children had AR, and the average age at AR was (4.38±1.08). The results of multifactorial logistic regression analysis showed that pre-pregnancy overweight (OR=1.67,95%CI:1.27-2.19), pre-pregnancy obesity (OR=3.05,95%CI:1.66-5.56), and maternal GDM (OR=1.40,95%CI:1.11-1.76) were risk factors for early AR timing in children. In contrast, pre-pregnancy underweight (OR=0.60,95%CI:0.49-0.73) was a protective factor for early AR timing in children. Compared with the different effects of pre-pregnancy overweight/obesity and maternal GDM alone, the combined effect caused a higher risk of early AR timing in children, with OR values (95%CI) were 2.03 (1.20-3.44), 3.43 (1.06-11.12), respectively. The multiplication and additive models showed no interaction between pre-pregnancy BMI and GDM-influenced early AR timing in children. Conclusion: Higher pre-pregnancy BMI and maternal GDM are the independent risk factors for the early AR timing in children, and the co-occurrence of the two is higher risks, but there was no statistical interaction.
Child ; Infant ; Female ; Pregnancy ; Humans ; Adiposity ; Diabetes, Gestational/epidemiology* ; Overweight/epidemiology* ; Thinness ; Cohort Studies ; Body Mass Index ; Obesity

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.
Autism Spectrum Disorder/therapy* ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects* ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.
Animals ; Drug Combinations ; Drugs, Chinese Herbal ; Endotoxemia/drug therapy* ; Rats

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

Objective:To investigate whether the adverse reactions of Xuebijing injection (XBJJ) are mainly pseudoallergic reactions and explore the influencing factors of its pseudoallergic reactions. Method:Mouse model of pseudoallergic reaction was used to study the anaphylactoid reaction of XBJJ which at 0.5, 1 and 2 times of the highest clinical concentration. Next, we compared the differences in pseudoallergic reactions caused by XBJJ for different storage times after preparation. Specifically, XBJJ was prepared into different concentrations, stored for 10 minutes, 2.5 hours, 6 hours and 24 hours, and then injected into the tail vein of mice. Finally, three different injection speeds of 3 seconds, 45 seconds and 90 seconds were selected for XBJJ injection, and then the differences in the paeudoallergic reactions induced by XBJJ in mice under different injection speeds were compared. Result:XBJJ induces pseudoallergic reactions in mice when the drug concentration is higher than the clinically recommended concentration. Compared with storage for 10 minutes after preparation, the degree of pseudoallergic reaction in mice induced by the same concentration of XBJJ increased with the extension of storage time. In addition, when XBJJ was injected in 3 s (the injection rate was 0.083 mL·s^-1), it produced the strongest pseudoallergic reaction. Conclusion:The adverse reactions induced by XBJJ are mainly pseudoallergic reactions. Excessive storage time after preparation and fast injection speed of XBJJ will lead to aggravation of pseudoallergic reactions in mice. When XBJJ is used clinically, it should strictly follow the usage, dosage, concentration, and drip rate recommended in the drug instruction manual. Rational drug use is of positive significance for improving the safety of XBJJ.

Objective:To summarize the clinical nursing experience of oxygenation (ECMO) adjuvant therapy in children with acute respiratory distress syndrome (ARDS) caused by severe adenovirus pneumonia.Method:The clinical data of 20 children with severe adenovirus pneumonia complicated with ARDS who received ECMO in our hospital from April 2017 to May 2019, including general conditions, pre-treatment, complications and prognosis, were retrospectively analyzed.Results:The primary disease of 20 patients was severe adenovirus pneumonia, and the average duration of ECMO treatment was [247.50(152.00,296.75)] hours. After treatment, 12 (12/20) patients successfully escaped from ECMO, 11 (11/20) patients died, and 9 (9/20) died. Complications occurred in 17 (17/20) patients with ECMO treatment. After discharge from the hospital for six months to two years, 9 patients with good quality of life, social function, normal mental development, 2 patients with ischemia and hypoxia brain damage, in the hospital or family continued rehabilitation exercise.Conclusions:Children with severe adenovirus pneumonia combined with ARDS are critically ill. When other treatments are ineffective, ECMO treatment can provide cardiopulmonary support for children with reversible cardiopulmonary failure, but the complications are numerous and serious. Prevention and reduction of related complications are the key to the success of ECMO.

Coronavirus disease-2019 (COVID-19) is an infectious disease caused by 2019 new coronavirus (2019-nCoV) infection. The disease is highly contagious and people are generally susceptible to it. New coronavirus pneumonia is mainly transmitted by respiratory droplets and close contact, but there is also a possibility of aerosol infection. At present, the outbreak of new coronavirus pneumonia has spread rapidly to all parts of the world. However, there is still no specific drug in clinical treatment. After the outbreak, the National Health Commission organized relevant experts to launch a series of diagnosis and treatment programs, including traditional Chinese medicine（TCM） treatment programs from the Trial Version 3. Chinese medicine injections were applied from the Trial Version 4. In this paper, the applications of Chinese medicine injections, which were recommended in the Trial Version 7 of Diagnosis and Treatment Protocol for COVID-19, in respiratory infectious diseases were summarized. Besides, the potential roles of Chinese medicine injections in the treatment of new coronavirus pneumonia were discussed, in order to provide theoretical basis for the reasonable application of Chinese medicine injection in COVID-19 treatment.

Objective:To investigate the therapeutic effect and possible mechanism of four types of Chinese herbal moisturizers made in laboratory for atopic dermatitis induced by 2，4-dinitrofluorobenzene （DNFB） in mice. Method:According to the body weight， BALA/c mice were randomly divided into normal group， model group， blank cream group （moisturizer A）， Shaoyao Gancaotang group （moisturizer B）， Shaoyao Gancaotang with Portulacae Herba，Ginseng Radix et Rhizoma and Honeysuckle Stem group （moisturizer C）， and Shaoyao Gancaotang with Ginseng Radix et Rhizoma and Honeysuckle Stem group （moisturizer D） ， with the dose of 25 g·kg^-1 per day， as well as tacrolimus ointment group of 3 g·kg^-1 per day， with 10 to 12 mice in each group. Except the normal group， the mice in the other groups were treated with 0.5% DNFB in the hair removal skin of back， 100 μL each for 7 days. Starting from the 7^th day， each group was given the appropriate skin cream for external use intervention， once per day， for 15 consecutive days， except for the normal and the model groups. The animal body mass was measured once a week， and the animal back skin was graded three times a week， and the skin lesion score was recorded. After the mice were killed， the left and right ears were taken， the weight of both ears was punched and the degree of swelling was calculated. The back skin was fixed and stained with hematoxylin-eosin（HE） method， and then pathologic examination was conducted to observe and score the pathological changes of mouse back skin. Blood was obtained after the last dose and enzyme-linked immunosorbent assay （ELISA） was used to determine the immunoglobulin（Ig）E content in serum. Western blot was used to measure the expression of signal transduction and activator of transcription 3 （STAT3）， phosphorylation （p）-STAT3 in the skin tissue. Result:Compared with the normal group， the body mass decreased continuously， a series of inflammatory changes such as erythema， edema， dryness， desquamation and callus exfoliation and so on occurred in the modeling area， and the skin lesion score increased significantly in the model group. Additionally， the cuticle of ear skin was thickened and the degree of ear swelling was obviously increased in the model group. Microscopically， the occurred changes in the model mice included the local necrosis of the epidermis， epidermal thickening， epidermal hyperplasia， and the hyperkeratosis and hypokeratosis in the cuticle， as well as the subcutaneous inflammatory cell infiltration and so on. Furthermore， the content of serum IgE andthe expression of p-STAT3 in skin tissues increased significantly in the model group. Compared with the model group， the body mass of mice in group C and D was significantly increased （P<0.01）， and the skin lesion status score was decreased （P<0.05，P<0.01）.The degree of auricle swelling was significantly reduced in group B， C and D compared with that in the model group （P<0.01）.The degree of skin necrosis and defect and epidermal hyperplasia of mice in moisturizer C group was significantly reduced compared with that in model group （P<0.05，P<0.01）. Serum IgE levels of mice in group C and D were significantly lower than those in the model group （P<0.05，P<0.01）. The expression of p-STAT3 protein in skin tissues of mice in moisturizer C group was significantly lower than that in model group （P<0.05）. Conclusion:The moisturizers B， C and D all have certain therapeutic effect on atopic dermatitis， among which moisturizers C has the most obvious therapeutic effect. The possible mechanism may be that it reduces the level of inflammatory cytokines by inhibiting the increase of serum IgE content and the phosphorylation of STAT3.