Objective:To investigate the correlation between complement C3 and urine protein level and proteinuria remission status in patients with primary membranous nephropathy (PMN), and better guide individualized clinical treatment.Methods:It was a single-center retrospective study. The clinical data of PMN patients who underwent renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2022 were collected. Patients with 24 h urinary protein ≥ 3.5 g were followed up after receiving standard treatment, and the last outpatient or inpatient review was used as the end point of follow-up. 24 h urine protein was collected to evaluate the remission status of proteinuria. Kaplan-Meier method was used to analyze the correlation between serum and renal complements and proteinuria remission. Cox regression analysis method was used to analyze the correlation between serum C3 level and renal tissue C3 deposition and proteinuria remission.Results:This study included 507 PMN patients with 312 (61.54%) males, aged 54 (43, 64) years old. Compared with 24 h urinary protein < 3.5 g group, proportion of males ( χ2=22.479, P<0.001), age ( Z=-2.521, P=0.012), systolic blood pressure ( Z=-4.148, P<0.001), diastolic blood pressure ( Z=-4.084, P<0.001), serum anti-phospholipase A2 receptor (PLA2R) antibody titer ( Z=-7.019, P<0.001), total cholesterol ( Z=-8.796, P<0.001), triglyceride ( Z=-6.158, P<0.001), low density lipoprotein cholesterol ( Z=-8.716, P<0.001), serum creatinine ( Z=-7.368, P<0.001), serum C3 ( Z=-3.663, P<0.001), serum C4 ( Z=-6.560, P<0.001), proportion of glucocorticoid use ( χ2=116.417, P<0.001) and proportion of immunosuppressant use ( χ2=53.839, P<0.001) were all higher, while serum albumin ( Z=12.518, P<0.001), estimated glomerular filtration rate ( Z=6.345, P<0.001) and serum IgG ( Z=7.321, P<0.001) were all lower in 24 h urinary protein ≥3.5 g group. There were 268 patients included in the follow-up cohort with baseline 24 h urinary protein of 7.15 (5.14, 10.24) g, serum anti-PLA2R antibody titer of 61.44 (14.35, 193.24) RU/ml, serum C3 of 1.005 (0.864, 1.150) g/L, and serum C4 of 0.260 (0.214, 0.317) g/L. Kaplan-Meier survival curve showed that the incomplete remission rate of proteinuria in serum C3 > 1.005 g/L group was lower than that in serum C3 ≤ 1.005 g/L group (log-rank χ2=4.757, P=0.029). There was no significant difference in the incomplete remission rate of proteinuria between serum C4 ≤ 0.260 g/L group and serum C4 > 0.260 g/L group (log-rank χ2=3.543, P=0.060). Renal C1q (log-rank χ2=0.167, P=0.683) and C4 (log-rank χ2=1.927, P=0.165) deposition had no significant effects on proteinuria remission in PMN patients. The incomplete remission rate of proteinuria in patients with renal C3 deposition was higher than that in patients without renal C3 deposition (log-rank χ2=7.018, P=0.008). Univariate Cox regression analysis showed that serum C3 level and C3 deposition in renal tissues were influencing factors of incomplete remission of proteinuria (both P<0.05), while adjusting for gender, age, mean arterial pressure, serum anti-PLA2R antibody, serum albumin and 24 h urinary protein, serum C3 ≤ 1.005 g/L ( HR=1.374, 95% CI 1.021-1.849, P=0.036), C3 deposition in renal tissues ( HR=1.949, 95% CI 1.098-3.460, P=0.023), and serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues ( HR=1.472, 95% CI 1.093-1.983, P=0.011) were independent influencing factors of incomplete remission of proteinuria. Conclusions:The serum C3 level and C3 deposition in renal tissues are closely related to urinary protein level and proteinuria remission status in PMN patients. The patients with higher urinary protein have higher serum C3. For patients with massive proteinuria, serum C3 ≤ 1.005 g/L, C3 deposition in renal tissues, serum C3 ≤ 1.005 g/L combined with C3 deposition in renal tissues are independent risk factors of incomplete remission of proteinuria.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

AIM To prepare cucurbitacin B nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method.With stabilizer type,stabilizer-drug ratio and homogeneous frequency as influencing factors,particle size and PDI as evaluation indices,the formulation was optimized by single factor test,after which the solubility and stability were determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of cucurbitacin B,physical mixture and cucurbitacin B nanosuspensions(10 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,8,10,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of cucurbitacin B,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was hydroxypropyl cellulose+sodium dodecyl sulfate(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-drug ratio,80 MPa for homogeneous pressure,and 12 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 200 nm,0.140 and-32 mV,respectively.The nanosuspensions demonstrated obviously higher solubility than that of raw medicine and physical mixture,along with good stability within 6 months.Cucurbitacin B existed in the nanosuspensions in an amorphous state.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened tmax(P<0.01),prolonged t1/2(P<0.05,P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 4.32 times as compared with that of raw medicine.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of cucurbitacin B.

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.
Aged ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Early Detection of Cancer ; Feces ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occult Blood

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

Objective:To explore the effect and mechanism of Xiangshenwan on ulcerative colitis （UC） induced by dextran sulfate sodium （DSS） in mice based on the classic Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） signaling pathway. Method:The experimental mice were divided into a normal group， a model group， a Xiangshenwan group， and a mesalazine group. The mice， except for those in the normal group， received 3% DSS solution for 7 days to establish the acute UC model and were treated with Xiangshenwan （5 g·kg^-1） and mesalazine （300 mg·kg^-1） continuously from the 1st day to the 10th day of modeling. The body weight， disease activity index （DAI）， colon weight， intestinal weight index， colon length， colon weight per unit length， and pathological changes of mice were evaluated respectively. The protein expression of TLR5， myeloid differentiation factor 88 （MyD88）， interleukin-1 receptor-associated kinase 4 （IRAK4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， transforming growth factor β-activated kinase 1 （TAK1）， p38 mitogen-activated protein kinase （MAPK）， NF-κB， IRAK1， TAK1-binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 3 （MKK3）， MKK6 and cyclic adenosine monophosphate response element-binding protein （CREB） in colon tissues of mice was detected by Western blot. Result:Compared with the normal group， the model group showed decreased body weight of mice， increased DAI scores， elevated colon weight， intestinal weight index， and colon weight per unit length， shortened colon length， severe colonic mucosal injury， and up-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-κB， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （P<0.05， P<0.01）. Compared with the model group， the Xiangshenwan group and the mesalazine group displayed increased body weight of mice， decreased DAI scores， declining colon weight， intestinal weight index， and colon weight per unit length， increased colon length， improved colonic mucosal injury， and down-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-κB， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （P<0.05， P<0.01）. Conclusion:Xiangshenwan can effectively treat DSS-induced UC presumedly by the inhibition of TLR/NF-κB signaling pathway.

Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms， quality of life， immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma （EC） operation. Method:Patients were divided into control group （82 cases） and observation group （86 cases） according to random number table. A total of 75 patients in control group completed the study （4 patients fell off or lose visit， and 3 patients were eliminated）， while 77 patients in observation group completed the study （5 patients fell off or lose visit， and 4 patients were deleted）. After operation， patients got brachytherapy， external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan， 1 pill/time， 2 times/day， and those in observation group got Dingkundan， 7 g/time， 2 times/day. The course of treatment lasted for 4 months， and long-time follow-up data was recorded. Before treatment， and at the second and fourth month after treatment， deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded， and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ and CD4⁺/CD8⁺） were detected， European collaborative quality of life Cancer Core Scale （EORTC QLQ-C30） was evaluated， and expressions of pce125 （CA125）， epididymis protein 4 （HE4）， Dickkopf-related protein-1 （DKK1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9） and transforming growth factor-β₁ （TGF-β₁） were tested before and after treatment. The follow-up was made for every three months， and the progression （recurrence/metastasis） of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment （P<0.01）. Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression， gastrointestinal toxicity， neurotoxicity were lower than those in control group （P<0.05）. Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group （P<0.01）， and scores of three symptom dimensions were lower than those in control group （P<0.01）. Levels of CD3⁺， CD4⁺ and CD4⁺/CD8⁺ were higher than those in the control group （P<0.01）， and CD8⁺ was lower than those in the control group （P<0.01）. Levels of CA125， HE4， DKK1， VEGF， MMP-9 and TGF-β₁ were lower than those in the control group （P<0.01）. The disease progression rate in observation group was 18.18% （14/77）， which was lower than 33.33% （25/75） in control group （χ²=4.572， P<0.05）. Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation， Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy， improve the quality of life and immune function， inhibit the expression of tumor markers and tumor growth factor， delay the progression of tumor and improve the prognosis.

This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Feces ; Plant Extracts ; Rats ; Rats, Sprague-Dawley ; Urticaceae

This work aimed to investigate the intestinal absorption characteristics of Laportea bulbifera extract in normal and rheumatoid arthritis model rats. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, galuteolin, quercetin and isoquercetin in intestinal absorption solution samples were detected by UPLC-MS/MS with 5.0 g·L~(-1) as the absorption concentration. The cumulative absorption(Q) and absorption rate constant(K_a) were calculated, and the absorption characteristics of different components of L. bulbifera in intestinal absorption solution of normal rats and rheumatoid arthritis rats were compared. The results showed that all the eight index components in the extract of L. bulbifera could be absorbed into the intestinal capsule, the cumulative absorption-time curve of each component showed an upward trend without saturation, and the correlation regression coefficient(R~2) was greater than 0.92, which is consistent with the zero-order absorption rate process. It was speculated that the possible absorption mode of each component was passive diffusion. In normal condition, the absorption of ileum was the best(except chlorogenic acid), and in pathological condition, duodenum was the best. The total absorption of 8 components in each intestinal segment of RA rats was better than that of normal rats, which speculated that rheumatoid arthritis may change the specific site of drug absorption. The experimental results showed that rheumatoid arthritis could change the intestinal absorption of the extract of L. bulbifera, and its mechanism needs further study.
Animals ; Arthritis, Rheumatoid/drug therapy* ; Chromatography, High Pressure Liquid ; Intestinal Absorption ; Intestines/drug effects* ; Plant Extracts/therapeutic use* ; Rats ; Tandem Mass Spectrometry ; Urticaceae/chemistry*