Which vaginal douching agent is the best choice before oocyte retrieval? A systematic review and network meta-analysis.

Objective: The aim of this study was to evaluate six vaginal douching agents (Iodine, Saline, Iodine followed by saline, chlorhexidine acetate followed by saline, Ozone, Potassium permanganate) on oocytes pick-up related pelvic infection (OPU-PI) and IVF outcome in patients underwent assisted reproduction technology (ART). Design: Through searching PubMed, Embase, Cochrane Library, Web of Science, Ovid, CINAHL CNKI, only human clinical trials were collected to study the effects of the six vaginal douching agents on OPU-PI and IVF outcomes. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. Results: The clinical trials were collected between the earliest available date and June 2022. Eight studies were included, the total sample size used in the study was 12,567. The results of the network meta-analysis showed that Ozone can significantly decrease OPU-PI; Iodine followed by saline can be a antiseptic protocol ranked first without affecting the quality of oocytes and Chlorhexidine acetate followed by saline can improve patients' clinical pregnancy rate. Conclusion: Based on Ranking Plot of the Network, this review reports the best evidence available regarding different vaginal douching agents used before OPU.

[Clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome combined with alveolar hypoventilation].

Objective: To evaluate the clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with alveolar hypoventilation. Methods: This retrospective study included patients who were diagnosed as OSAHS by polysomnography (PSG) and underwent daytime awake transcutaneous carbon dioxide (PtcCO2) monitoring from November 2019 to February 2021 at the Sleep Center of the Second Affiliated Hospital of Soochow University. A total of 177 patients were enrolled in the analysis, including 167 males and 10 females, aged (40±8) years old. Patients with daytime awake PtcCO2>45 mmHg (1 mmHg=0.133 kPa) were diagnosed as daytime alveolar hypoventilation, with which participants were divided into the daytime alveolar hypoventilation group and non-daytime alveolar hypoventilation group. Body mass index (BMI) cut-off value predicting daytime alveolar hypoventilation was calculated and the patients were divided into the high BMI group and low BMI group. The continuous nocturnal PtcCO2 data was available for a subset of 128 patients, and the patients were divided into two groups according the daytime alveolar hypoventilation or not. Across-group differences were compared, respectively. Results: Compared with the non-daytime alveolar hypoventilation group (n=125), the BMI [27.57 (26.55, 30.33) vs 26.60 (25.06, 28.09) kg/m2], Epworth sleepiness score(ESS) score [9.50 (6.25, 12.00) vs 7.00 (4.00, 10.75)], higher oxygen desaturation index (ODI) [38.00 (15.23, 64.93) vs 26.80 (11.30, 44.30) events/h] and percentage of total time with oxygen saturation level<90% (TS90%) [11.24% (1.88%, 32.44%) vs 4.35% (0.72%, 9.87%)] of the daytime alveolar hypoventilation group(n=52) were significantly higher (P<0.05), and lowest arterial oxygen saturation (LSaO2) [74.50% (60.25%, 82.00%) vs 79.00% (73.00%, 84.50%)], mean arterial oxygen saturation (MSaO2) [94.00% (91.00%, 95.00%) vs 95.00% (94.00%, 96.00%)] were significantly lower (P<0.05). The BMI cut-off value for predicting daytime alveolar hypoventilation was 27.04 kg/m2. Of the 177 enrolled patients, 90 were in the high BMI group and 87 were in low group. Compared with the low BMI group, the proportion of daytime sleepiness, the ESS score, the prevalence of hypertension, AHI and daytime awake PtcCO2 in the high BMI group were significantly higher (P<0.05). Among the subset of 128 patients with nocturnal PtcCO2 data available, the BMI, daytime PtcCO2 level, the nocturnal CO2 level and the prevalence of sleep related alveolar hypoventilation in the daytime alveolar hypoventilation group (n=40) were significantly higher than those in the non-daytime alveolar hypoventilation group (n=88) (P<0.05). Conclusions: The OSAHS patients with alveolar hypoventilation have higher BMI and more severe nocturnal hypoxia. OSAHS patients with BMI>27.04 kg/m2 are more likely to develop sleep related alveolar hypoventilation disorder.

[Optimal timing of antiviral therapy for chronic HBV-infected patients with normal ALT].

Whether to initiate antiviral therapy in chronic hepatitis B virus (HBV) infected population with normal alanine aminotransferase (ALT) is hot and difficult issue. Improvements in drug availability and affordability have paved the way for more data, which may become a medium for confirming whether this population needs antiviral treatment. Regardless of whether HBeAg is positive or negative, there are still a considerable number of patients with chronic HBV infection with normal ALT, who have obvious liver inflammation, fibrosis or cirrhosis and need to start antiviral therapy. Liver biopsy or non-invasive techniques can be used as diagnostic tools to begin an early treatment in population with liver fibrosis and inflammation.

Primary yolk sac tumour of the prostate mimicking small round blue cell tumour.

Prostatic yolk sac tumour is a germ cell tumour with a wide range of age of occurrence, unusual anatomic locations, diverse morphologic patterns, and aggressive biologic behavior, posing challenges both to diagnosis and clinical management. We report a rare case of primary yolk sac tumour of the prostate with extensive local and liver metastasis, the latter of which exhibited sheets of small blue cells expressing CD99 and focal sall4 on biopsy. Positivity for CD99 and gata3 in the initial biopsy raised the differential diagnosis of Ewing sarcoma and poorly differentiated carcinoma. The primary tumour demonstrated an admixture of solid and glandular growth patterns and occasional Schiller-Duval bodies. A panel of immunohistochemical stains showing positivity for AE1/3, sall4, cdx2, and focal alpha-fetoprotein, and negativity for oct-4, facilitated the diagnosis. A thorough review of the literature and our current report indicate that a large tumour load, incomplete tumour resection, limited response to preoperative neoadjuvant chemotherapy, and late stage of the disease are predictive factors for a poor clinical outcome.

The re-emerging of SADS-CoV infection in pig herds in Southern China.

A new highly virulent swine acute diarrhoea syndrome coronavirus (SADS-CoV) emerged in Guangdong province in 2017 followed by fatal diarrhoea that involved the death of 24,693 piglets. And yet from May 2017 to January 2019, there were no new SADS cases arising in pig herds in Guangdong. In this study, we reported the recent diarrhoea outbreak of SADS-CoV in Southern China on February 2019. Intestinal samples collected from diarrhoeal piglets were detected for common swine virus and confirmed that SADS-CoV was responsible for the diarrhoea case. Meanwhile, serological investigation of sows' sera implied that SADS-CoV has existed in the farm and PEDV antibody may not directly contribute to the amplification of SADS-CoV. Homology and phylogenetic analysis of the whole genome showed that the re-emerging SADS-CoV strain shared high sequence identities with existing SADS-CoV strains and all strains clustered together in Alpha coronavirus. All in all, the report herein emphasized the re-emerging of SADS-CoV and highlights continuous monitoring for this virus.

Analysis of Genetic Polymorphism and Genetic Distance of 19 Autosomal STR Loci in Jiangsu Han Population.

OBJECTIVES: To investigate the distribution of alleles in 19 autosomal short tandem repeat （STR） loci in Jiangsu Han population. METHODS: Goldeneye® 20A kit was used to detect 9 025 samples. Genetic analysis was performed on typing data of 19 autosomal STR loci, and genetic distance with other 17 populations was analyzed. RESULTS: All the 19 autosomal STR loci were consistent with the Hardy-Weinberg equilibrium （P>0.05）, with the heterozygosity 0.616 1-0.916 3, probability of match 0.012 8-0.202 6, discrimination power 0.797 4-0.987 2, probability of paternity exclusion 0.310 8-0.828 8, and polymorphic information content 0.561 7-0.913 6. The cumulative discrimination power and cumulative probability of exclusion were 0.999 999 999 999 999 998 434 1 and 0.999 999 989, respectively. The Jiangsu Han population had close genetic distances with the Han population in Tianjin, Hunan and Jilin, and significant difference with Han population in Aletai region in Xinjiang （P<0.05）. CONCLUSIONS: The STR allele polymorphism data and population genetic parameters of Jiangsu Han population can provide data support for the forensic application of these STR loci in Jiangsu Han population.

SNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese.

Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation. The performance of our new panel was compared to a recent Han Chinese panel. Finally, genetic associations of HLA variants with mild skin rash were performed on the combined sample of 408 patients. Common SNPs rs2571375 and rs144295468 were found to successfully tag HLA risk alleles A*31:01 and B*13:01, respectively. HLA-B*15:02 can be predicted by rs144012689 with >95% sensitivity and specificity. The imputation reference panel for the Hong Kong population had comparable performance to the Han Chinese panel due to the large sample size for common HLA alleles, though it retained discordance for imputing rare alleles. No significant genetic associations were found between HLA genetic variants and mild skin rash induced by aromatic antiepileptic drugs. This study provides new information on the genetic structure of HLA regions in the Hong Kong population by identifying tagging SNPs and serving as a reference panel. Moreover, our comprehensive genetic analyses revealed no significant association between HLA alleles and mild skin rash in Hong Kong Han Chinese.

The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL.

The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives. A total of 928 consecutive patients with prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12-core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy.

Influence of interleukin-18 gene polymorphisms on acute pancreatitis susceptibility in a Chinese population.

We investigate the relationship between IL-18 -607C/A and -137G/C genetic polymorphisms and development of acute pancreatitis in a Chinese population. A total of 153 patients were consecutively recruited from the First Affiliated Hospital of Chongqing Medical University between January 2013 and November 2014. Genotyping of IL-18 -607C/A and -137G/C variants was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We observed a significant difference between acute pancreatitis patients and control subjects with respect to age (t = 2.15, P = 0.02), gender (chi-square = 3.95, P = 0.04), body mass index (t = 5.85, P < 0.001), and alcohol consumption (chi-square = 9.74, P = 0.002). Using chi-square tests, we found that the genotype distributions of IL-18 -607C/A (chi-square = 0.81, P = 0.67) and -137G/C (chi-square = 1.16, P = 0.56) polymorphisms did not differ between the acute pancreatitis and control groups. Genotype frequencies of these variants were consistent with Hardy-Weinberg equilibrium in both patient and control groups. In addition, logistic regression analysis failed to identify a significant association between these polymorphisms and acute pancreatitis risk. Our study firstly examined their association in a Chinese population, and we suggest that the IL-18 -607C/A and -137G/ C polymorphisms do not influence susceptibility to acute pancreatitis in the Chinese population studied in the present study.

Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease.

BACKGROUND: This study aimed to investigate the possible synergistic effects of lipid disorder with renin-angiotensin system (RAS) activation in non-alcoholic fatty liver disease (NAFLD). METHODS: Apolipoprotein E gene-knockout mice, angiotensin II (Ang II) type 1 receptor (AT1) gene-knockout mice and human hepatoblastoma cell line (HepG2) were used for experiments. Lipid accumulation was examined by Filipin staining and intracellular cholesterol quantitative assay. The gene and protein expression of molecules involved in RAS and low-density lipoprotein receptor (LDLr) pathway was examined by real-time PCR, immunofluorescent staining and Western blot. RESULTS: There was significantly increased expression of RAS components and extracellular matrix (ECM) in livers of high-fat-diet-fed apolipoprotein E gene-knockout mice compared with controls. Upregulation of RAS components was positively associated with increased plasma levels of lipid profile. The in vitro study further confirmed that cholesterol loading increased supernatant renin activity and Ang II level of HepG2 cells, accompanied by increased ECM production that was positively associated with increased expression of intracellular RAS components. Interestingly, Ang II treatment increased lipid accumulation in livers of C57BL/6 mice and HepG2 cells. Furthermore, Ang II treatment increased gene and protein expression of sterol regulatory element-binding protein (SREBP) cleavage activating protein (SCAP), SREBP-2 and LDLr, which were mediated by enhanced SCAP/SREBP-2 complex translocation from endoplasmic reticulum to Golgi. However, LDLr pathway was accordingly downregulated in livers of AT1 gene-knockout C57BL/6 mice or in HepG2 cells treated by telmisartan. CONCLUSION: These findings demonstrate that lipid disorder and intrahepatic RAS activation synergistically accelerate NAFLD progression.

Chemokine (C-C Motif) Receptor 2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon.

BACKGROUND & AIMS: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/- subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. RESULTS: Colonic DC identified were myeloid (mDC, CD11c+CD123-) and further divided based on CD103 and SIRPα (human analog of murine CD11b) expression. CD103-SIRPα+ DC were the major population and with CD103+SIRPα+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPα+ DC). CD103+SIRPα- DC constituted a minor subset that were CD141+ILT3-CCR2-. Proximal colon samples had higher total DC counts and fewer CD103+SIRPα+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (ß7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. CONCLUSIONS: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization.

Impact of tailored feedback in assessment of communication skills for medical students.

BACKGROUND: Finding out the effective ways of teaching and assessing communication skills remain a challenging part of medication education. This study aims at exploring the usefulness and effectiveness of having additional feedback using qualitative analysis in assessment of communication skills in undergraduate medical training. We also determined the possibilities of using qualitative analysis in developing tailored strategies for improvement in communication skills training. METHODS: This study was carried out on medical students (n=87) undergoing their final year clinical performance examination on communication skills using standardized patient by video-recording and transcribing their performances. Video-recordings of 26 students were randomly selected for qualitative analysis, and additional feedback was provided. We assessed the level of acceptance of communication skills scores between the study and nonstudy group and within the study group, before and after receiving feedback based on qualitative analysis. RESULTS: There was a statistically significant increase in the level of acceptance of feedback after delivering additional feedback using qualitative analysis, where the percentage of agreement with feedback increased from 15.4 to 80.8% (p<0.001). CONCLUSIONS: Incorporating feedback based on qualitative analysis for communication skills assessment gives essential information for medical students to learn and self-reflect, which could potentially lead to improved communication skills. As evident from our study, feedback becomes more meaningful and effective with additional feedback using qualitative analysis.

Prognostic Value of the Tumour-Infiltrating Dendritic Cells in Colorectal Cancer: A Systematic Review.

Dendritic cells (DCs) either boost the immune system (enhancing immunity) or dampen it (leading to tolerance). This dual effect explains their vital role in cancer development and progression. DCs have been tested as a predictor of outcomes for cancer progression. Eight studies evaluated tumour-infiltrating DCs (TIDCs) as a predictor for colorectal cancer (CRC) outcomes. The detection of TIDCs has not kept pace with the increased knowledge about the identification of DC subsets and their maturation status. For that reason, it is difficult to draw a conclusion about the performance of DCs as a predictor of outcome for CRC. In this review, we comprehensively examine the evidence for the in situ immune response due to DC infiltration, in predicting outcome in primary CRC and how such information may be incorporated into routine clinical assessment.

Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.

Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase.

Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (≤ 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change.

Investigation of lectin-modified insulin liposomes as carriers for oral administration.

The aim of this study was to design and characterize lectin-modified liposomes containing insulin and to evaluate the potential of these modified colloidal carriers for oral administration of peptide and protein drugs. Wheat germ agglutinin (WGA), tomato lectin (TL), or Ulex europaeus agglutinin 1 (UEA1) were conjugated by coupling their amino groups to carbodiimide-activated carboxylic groups of N-glutaryl-phosphatidylethanolamine (N-glut-PE). Insulin liposomes dispersions were prepared by the reverse-phase evaporation technique and modified with the lectin-N-glut-PE conjugates. Lectin-modified liposomes were characterized according to particles size, zeta potential and entrapment efficiency. The hypoglycemic effect indicated by pharmacological bioavailability of insulin liposomes modified with WGA, TL and UEA1 were 21.40, 16.71 and 8.38% in diabetic mice as comparison with abdominal cavity injection of insulin, respectively. After oral administration of the insulin liposomes modified with WGA, TL and UEA1 to rats, the relative pharmacological bioavailabilities were 8.47, 7.29 and 4.85%, the relative bioavailability were 9.12, 7.89 and 5.37% in comparison with subcutaneous injection of insulin, respectively. In the two cases, no remarkable hypoglycemic effects were observed with the conventional insulin liposomes. These results confirmed that lectin-modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.

[Studies on the chemical constituents of Annona muricata].

Annonaceous acetogenin (or polyketide) is a kind of potential antineoplastic agents from Annonaceae plants. Two new acetogenins, Muricatalicin (I) and muricatalin (VI), a mesitoate of a new acetogenin, annonacin-B mesitoate (Vb), and three known acetogenins, annonacin (II), annonacin-A (III) and annonacin-10-one (IV) have been isolated from Annona muricata L. The structures and relative stereochemistry of I, VI and Vb were elucidated on the basis of spectral analysis and examination of their acetates and/or mesitoate.