[Analysis on the iron status and associated factors during the first trimester of pregnancy].

OBJECTIVE: To investigate the impact of dietary and underlying factors on the iron status of women in early pregnancy and to provide evidence for preventing iron deficiency and iron deficiency anemia, thereby reducing the incidence of associated adverse outcomes. METHODS: From November to December 2018, women in the first trimester of pregnancy (< 12 weeks gestation) who established prenatal records at the Shunyi District Maternal and Child Health Hospital, Beijing, were enrolled in this study, in which 388 participants were accessed for data including demographic characteristics, anthropometric measurements, parity, biomarkers reflecting iron status, and food-frequency questionnaire. SPSS 26.0 were used for statistical analysis. Dietary patterns were extracted using principal component analysis, and factor scores of each dietary pattern were calculated. Two-sided Fisher exact probability test and one-way ANOVA were conducted to access differences in iron status among the groups, and the differences were significant if P < 0.05. Iron deficiency was defined as serum ferritin(SF) < 30 µg/L. To analyze the potential role of dietary factors on iron deficiency during the first trimester, the collected data listed above were adopted as independent factors for the cross-sectional Logistic regression. We used Logistic regression to analyze the potential effects of baseline characteristics and dietary factors on iron status. RESULTS: Among the 388 participants included in the analysis, 121 (32.2%) were iron deficient, in which 107 (27.6%) were iron depletion (ID), 8 (2.1%) were iron deficiency erythropoiesis (IDA), 6(1.5%) were iron deficiency anemia. The mean SF concentration was (50.4±35.3) µg/L. Multiparity(OR=3.9, 95%CI: 1.81-8.42, P=0.001)was a risk factor for iron deficiency during early pregnancy. No significant iron status differences were found among the participants with different educational levels and anthropometric measurements. In contrast, age (OR =0.96, 95%CI: 0.94-0.97, P < 0.001) was a protective factor. For multiparas, taking iron-containing supplements might have a protective effect for iron deficiency (OR=0.27, 95%CI: 0.09-0.83, P=0.022). The balance-diet pattern (OR=0.81, 95%CI: 0.66-1.00, P=0.054) only showed a marginally significant effect. CONCLUSION: Increasing attention should be paid to the iron status of pregnant multiparas and young pregnant women. For those women of reproductive age with the risk factors listed above, especially for multiparas, iron-containing supplements should be recommended to prevent gestational iron deficiency. The effect of the "balance" dietary pattern on iron status in the first trimester and following requires further research and discussion.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Clinical application of laparoscopic sentinel lymph node mapping in early staged cervical cancer].

Objective: To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy. Methods: It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer. Results: The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 (P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions: SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

[Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria].

Objective: To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored. Methods: The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children's Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively. Results: There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions: The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Effects of fish oil-derived fatty acids on suboptimal cardiovascular health: A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Suboptimal health and metabolic disorders are common in the general population. Both are related to cardiovascular disease. Suboptimal cardiovascular health is defined by the presence of both suboptimal health and metabolic disorders. The aim of the study was to investigate the potential benefit of n-3 long-chain polyunsaturated fatty acids (LCPUFA) in participants with suboptimal cardiovascular health. METHODS AND RESULTS: A total of 422 participants with suboptimal cardiovascular health, from two clinics in China, were enrolled from September 2014 to April 2015. All the enrolled participants were randomly assigned to receive 4 g/d of fish oil or placebo for three months. Suboptimal health was defined using an accepted questionnaire. Metabolic disorders were defined as one or more abnormalities in blood pressure, fasting plasma glucose, blood lipids, and body mass index (BMI). After treatment, the mean BMI fell significantly more in the n-3 LCPUFA group than in the placebo group (-0.29 ± 0.06 kg/m2 vs. -0.02 ± 0.06 kg/m2, P = 0.003). Similar results were found in the changes of suboptimal health status and suboptimal cardiovascular health status (P < 0.05 for all). In a multivariate analysis, the n-3 LCPUFA group was 5.44 (1.15, 25.67) times more likely to have optimal cardiovascular health status after treatment. CONCLUSIONS: n-3 LCPUFA intake improved suboptimal cardiovascular health in this placebo-controlled, randomized, double-blind trial. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT02103517.

[Two cases with generalized intracranial calcification due to hereditary folate malabsorption and literature review].

Objective: This study aimed to investigate the clinical, biochemical and genetic features of two Chinese children with hereditary folate malabsorption. Method: Clinical features, laboratory examinations, treatment and SLC46A1 gene of two cases were studied. Reports on hereditary folate malabsorption utill September of 2016 were searched and the clinical and genetic characteristics of reported cases were summarized. Result: The two patients presented with megaloblastic anemia from their infant period and seizures, psychomotor retardation and regression. In case1, mean corpuscular volume (MCV) was 100 fl. Serum folate was 9.96 nmol/L. Folate and 5-methylenetetrahydrofolate in cerebrospinal fluid were 0 and 0.01 separately. In case 2, MCV was 93.9 fl. Serum folate was 4.49 nmol/L. The concentration of folate and 5-methylenetetrahydrofolate in cerebrospinal fluid were both zero. On their brain CT, progressive bilateral symmetrical calcification was observed. On their SLC46A1 gene, four mutations were identified. Case 1 had one novel mutation, c. 1238T>C (L413P) and c. 194-195insG (p.Cys66LeufsX99). From Case 2, two reported mutations, c. 1A>T (M1L) and c. 194-195insG (p.Cys66LeufsX99) were identified. The administration of folinic acid (60 to 120 mg per day) was initiated after diagnosis. Clinical improvement and normalized hematologic markers were observed after treatment. Totally 37 cases were reported in reviewed English literature, including 30 cases with mutations on SLC46A1 gene (only one Chinese patient). All the cases had the onset in infancy. The ratio of boys to girls was 1 to 1.5. Main manifestations were characterized by megaloblastic anemia (77%), failure to thrive (50%), diarrhea (27%), psychomotor retardation (63.6%), epilepsy (27%), and infection of respiratory system (45.5%). The concentration of folate in both serum and cerebrospinal fluid was decreased (72.7% and 63.6% respectively). Hypoimmunoglobulinemia accounted for 27.3%. Most of mutations in HFM were distributed between p. 65 and p. 68 (c.194-c.204), mainly due to insertion- or deletion-related frame shifts or generation of stop codons. Oral and parenteral folinic acid treatment was effective. Conclusion: Hereditary folate malabsorption often presented with megaloblastic anemia, abnormalities of digestive and nervous system, and hypoimmunoglobulinemia with recurrent infections. Low level of serum and CSF folate and screening SLC46A1 gene are keys to the etiologic study of the patients. Early supplement with folinic acid is beneficial to the prognosis.

Expression of ß-defensins in intestines of chickens injected with vitamin D3 and lipopolysaccharide.

The objective of this study was to evaluate the effect of vitamin D3 (VD3) on the regulation of chicken intestinal ß-defensin genes under normal and lipopolysaccharides (LPS) conditions. Four treatment groups were used, including a negative control group, VD3-injection group, LPS-injection group, and both VD3-injection and LPS-injection group. At 4, 24, and 48 h post-injection, intestines were collected and RNA was isolated to measure the chicken ß-defensin genes with putative vitamin D responsive elements using quantitative polymerase chain reaction. Expressions of all 7 chicken ß-defensin genes was detectable in the intestines. Significant increases in GAL-6, -7 and -9 were found following LPS injection treatment at 4, 24, and 48 h post-injection, respectively, whereas VD3 injection did not affect the expression of any investigated genes under normal conditions. However, the expression of GAL-4, -5, -6, and -10 were synergistically upregulated by VD3 in combination with LPS. These results suggest that VD3 enhances the immune immunity during LPS challenge by inducing the expression of chicken ß-defensin genes when birds are exposed to immune stressors.

The performance of enhanced coagulation for treating slightly polluted raw water combining polyaluminum chloride with variable charge soil.

The feasibility and effectiveness of treating pollutants in slightly polluted raw water by variable charge soil and polyaluminum chloride (PAC) was investigated. Removal efficiencies of turbidity, phenol, aniline, algae and heavy metals (Cu(2+), Zn(2+) and Pb(2+)) were used to evaluate the coagulation performance. The results indicated that the addition of variable charge soil as a coagulant aid is advantageous due to the improvement of removal efficiencies. The tests also demonstrated that the presence of variable charge soil increased the removal of turbidity rather than adding residuary turbidity. The use of variable charge soil produced settleable flocs of greater density and bigger size. The main mechanism involved in the PAC coagulation was supposed to be sweep flocculation as well as charge-neutralization. Variable charge soil played a promoted aid role by adsorption in the enhanced coagulation process. It is concluded that the enhanced coagulation by PAC and variable charge soil, as coagulant and adsorbent, is more effective and efficient than traditional coagulation.

Nucleotide receptor P2RX7 stimulation enhances LPS-induced interferon-ß production in murine macrophages.

Stimulation of P2RX(7) with extracellular ATP potentiates numerous LPS-induced proinflammatory events, including cytokine induction in macrophages, but the molecular mechanisms underlying this process are not well defined. Although P2RX(7) ligation has been proposed to activate several transcription factors, many of the LPS-induced mediators affected by P2RX(7) activation are not induced by P2RX(7) agonists alone, suggesting a complementary role for P2RX(7) in transcriptional regulation. Type I IFN production, whose expression is tightly controlled by multiple transcription factors that form an enhanceosome, is critical for resistance against LPS-containing bacteria. The effect of purinergic receptor signaling on LPS-dependent type I IFN is unknown and would be of great relevance to a diverse array of inflammatory conditions. The present study demonstrates that stimulation of macrophages with P2RX(7) agonists substantially enhances LPS-induced IFN-ß expression, and this enhancement is ablated in macrophages that do not express functional P2RX(7) or when the MAPK MEK1/2 pathways are inhibited. Potentiation of LPS-induced IFN-ß expression following P2RX(7) stimulation is likely transcriptionally regulated, as this enhancement is observed at the IFN-ß promoter level. Furthermore, P2RX(7) stimulation is able to increase the phosphorylation and subsequent IFN-ß promoter occupancy of IRF-3, a transcription factor that is critical for IFN-ß transcription by TLR agonists. This newly discovered role for P2RX(7) in IFN regulation may have implications in antimicrobial defense, which has been linked to P2RX(7) activation in other studies.

[Nuclear ribosomal RNA small subunit (18S rRNA) nucleotide sequencing and characterization of sailonggu(whole bone of Myospalax baileyi Thomas)].

OBJECTIVE: Sequencing the nuclear ribosomal RNA small subunit (18S rRNA) gene of Myospalax baileyi (Cricetidae) to develop an ultimate and definitive means for origin identification of genuine Sailonggu. METHODS: The total DNA was prepared from dried tail tissues. The nuclear 18S rRNA gene region was amplified by PCR using a consensus primer set and its nucleotide sequence was determined by PCR direct sequencing. The characteristic analysis of 18S rRNA sequences was generated using software program Genetyx-SV/R Version 10.1. RESULTS: The entire 18S rRNA gene region of M. baileyi spanded 1851 bp in length. Although multiple alignment of sequence indicates that there are only lower homology (72.04%-72.18%) comparing with its two alias Mus musculus (GenBank Accession number X00686) and Rattus norvegicus (M11188) (Muridae), their highly conservative domain is located in 1020-1509 nt. There are many variable sites from upstream of 5'-end, which could provide a novel information for molecular recognition of Sailonggu. CONCLUSION: DNA sequencing could be a useful and reliable tool in the origin identification of genuine Sailonggu.

Effect of alpha-hederin on hepatic detoxifying systems in mice.

AIM: To examine whether alpha-hederin (Hed) modulates hepatic detoxifying systems as a means of hepatoprotection. METHODS: Mice were injected Hed 10 and 30 mumol.kg-1 sc for 3 d, and liver cytosols were prepared 24 h after the last dose to study antioxidant enzymes and nonenzymatic defense components. RESULTS: Hed increased liver glutathione (GSH) content (20%), but had no effect on GSH peroxidase, GSH reductase, and GSH S-transferase. The activities of superoxide dismutase and quinone reductase were unaffected by Hed treatment. At the high dose of Hed, catalase activity was decreased by 20%. Hepatic content of metallothionein was dramatically increased (50-fold), along with elevations of hepatic Zn and Cu concentrations (25%-80%). Hed also increased ascorbic acid concentration (20%), but no effect on alpha-tocopherol in liver. CONCLUSION: Hed enhanced some nonenzymatic antioxidant components in liver, which play a partial role in Hed protection against hepatotoxicity produced by some chemicals.