Type I Mirizzi syndrome treated by electrohydraulic lithotripsy under the direct view of SpyGlass: A case report.

BACKGROUND: Mirizzi syndrome is an uncommon clinical complication for which the available treatment options mainly include open surgery, laparoscopic surgery, endoscopic retrograde cholangiopancreatography (ERCP), electrohydraulic lithotripsy, and laser lithotripsy. Here, a patient diagnosed with type I Mirizzi syndrome was treated with electrohydraulic lithotripsy under SpyGlass direct visualization, which may provide a reference to explore new treatments for Mirizzi syndrome. CASE SUMMARY: This paper describes a middle-aged female patient with suspected choledocholithiasis who complained for over 1 mo of intermittent abdominal pain, dark yellow urine, jaundice, and was proposed to undergo ERCP lithotomy. Mirizzi syndrome was found during the operation and confirmed by SpyGlass. Electrohydraulic lithotripsy was performed under the direct vision of SpyGlass. After the lithotripsy, the stones were extracted using the stone extraction basket and balloon. After the operation, the patient developed transient hyperamylasemia. Through a series of symptomatic treatments (such as fasting, fluids and anti-inflammation medications), the symptoms of the patient improved. Finally, laparoscopic cholecystectomy or open cholecystectomy was performed after a half-year post-operatively. CONCLUSION: Direct visualization-guided laser or electrohydraulic lithotripsy with SpyGlass is feasible and minimally invasive for type I Mirizzi syndrome without apparent unsafe outcomes.

Maternal weight, blood lipids, and the offspring weight trajectories during infancy and early childhood in twin pregnancies.

BACKGROUND: The intrauterine environment has a profound and long-lasting influence on the health of the offspring. However, its impact on the postnatal catch-up growth of twin children remains unclarified. Therefore, this study aimed to explore the maternal factors in pregnancy associated with twin offspring growth. METHODS: This study included 3142 live twin children born to 1571 mothers from the Beijing Birth Cohort Study conducted from 2016 to 2021 in Beijing, China. Original and corrected weight-for-age standard deviation scores of the twin offspring from birth to 36 months of age were calculated according to the World Health Organization Child Growth Standards. The corresponding weight trajectories were identified by the latent trajectory model. Maternal factors in pregnancy associated with the weight trajectories of the twin offspring were examined after adjustment for potential confounders. RESULTS: Five weight trajectories of the twin children were identified, with 4.9% (154/3142) exhibiting insufficient catch-up growth, 30.6% (961/3142), and 46.8% (1469/3142) showing adequate catch-up growth from different birth weights, and 15.0% (472/3142) and 2.7% (86/3142) showing various degrees of excessive catch-up growth. Maternal short stature [adjusted odds ratio (OR) = 0.691, 95% confidence interval (CI) = 0.563-0.848, P = 0.0004] and lower total gestational weight gain (GWG) (adjusted OR = 0.774, 95% CI = 0.616-0.972, P = 0.03) were associated with insufficient catch-up growth of the offspring. Maternal stature (adjusted OR = 1.331, 95% CI = 1.168-1.518, P < 0.001), higher pre-pregnancy body mass index (BMI) (adjusted OR = 1.230, 95% CI = 1.090-1.387, P < 0.001), total GWG (adjusted OR = 1.207, 95% CI = 1.068-1.364, P = 0.002), GWG rate (adjusted OR = 1.165, 95% CI = 1.027-1.321, P = 0.02), total cholesterol (TC) (adjusted OR = 1.150, 95% CI = 1.018-1.300, P = 0.03) and low-density lipoprotein-cholesterol (LDL-C) (adjusted OR = 1.177, 95% CI = 1.041-1.330) in early pregnancy were associated with excessive growth of the offspring. The pattern of weight trajectories was similar between monochorionic and dichorionic twins. Maternal height, pre-pregnancy BMI, GWG, TC and LDL-C in early pregnancy were positively associated with excess growth in dichorionic twins, yet a similar association was observed only between maternal height and postnatal growth in monochorionic twins. CONCLUSION: This study identified the effect of maternal stature, weight status, and blood lipid profiles during pregnancy on postnatal weight trajectories of the twin offspring, thereby providing a basis for twin pregnancy management to improve the long-term health of the offspring.

A novel dimension reduction algorithm based on weighted kernel principal analysis for gene expression data.

Gene expression data has the characteristics of high dimensionality and a small sample size and contains a large number of redundant genes unrelated to a disease. The direct application of machine learning to classify this type of data will not only incur a great time cost but will also sometimes fail to improved classification performance. To counter this problem, this paper proposes a dimension-reduction algorithm based on weighted kernel principal component analysis (WKPCA), constructs kernel function weights according to kernel matrix eigenvalues, and combines multiple kernel functions to reduce the feature dimensions. To further improve the dimensional reduction efficiency of WKPCA, t-class kernel functions are constructed, and corresponding theoretical proofs are given. Moreover, the cumulative optimal performance rate is constructed to measure the overall performance of WKPCA combined with machine learning algorithms. Naive Bayes, K-nearest neighbour, random forest, iterative random forest and support vector machine approaches are used in classifiers to analyse 6 real gene expression dataset. Compared with the all-variable model, linear principal component dimension reduction and single kernel function dimension reduction, the results show that the classification performance of the 5 machine learning methods mentioned above can be improved effectively by WKPCA dimension reduction.

Progress in immunotherapy for small cell lung cancer.

Small-cell lung cancer (SCLC) is a special type of lung cancer that belongs to highly aggressive neuroendocrine tumors. At present, radiotherapy and chemotherapy remain the mainstay of treatment for SCLC. Progress in targeted therapies for SCLC with driver mutations has been slow, and these therapies are still under investigation in preclinical or early-phase clinical trials, and research on antiangiogenic tyrosine kinase inhibitors (e.g., anlotinib) has achieved some success. Immunotherapy is becoming an important treatment strategy for SCLC after radiotherapy and chemotherapy. In this article we review the recent advances in immunotherapy for SCLC.

Six generations of epidermolytic palmoplantar keratoderma, associated with a KRT9 R163W mutation.

Epidermolytic palmoplantar keratoderma (EPPK) is a rare autosomal dominant skin disorder characterized by diffuse hyperkeratosis on the palms and soles. Whole-exome sequencing (WES) has become a powerful tool for the detection of rare causal variants of Mendelian disorders. However, no causal gene for EPPK in the Uygur population has been identified until now, and no treatment exists than can address the underlying pathology.WES analysis was undertaken on two individuals from a large Uygur EPPK pedigree whose disease locus mapped to 17q21.2 (chr:38994621-39893408) following previous linkage analysis. KRT9 (NM_000226.3:c.487C>T, p.Arg163Trp), and KRT15 (XM_005257346.1:c.212G>T, XP_005257403.1:p.Gly71Val) located in this region, have been identified as two candidate causative genes for EPPK in the Uygur family. Sanger sequencing was conducted on this region in other affected individuals (n = 38) from this family, non-affected individuals (n = 56) from this family and 100 unrelated controls. The missense mutation KRT9 c.487C>T, identified in this large Uygur population, is a potential causative mutation. To date, EPPK has no effective therapy, and siRNA is a potential avenue for EPPK therapy. To investigate this, full-length wild-type Keratin9 (KRT9; pKRT9-WT) and p.Arg163Trp (pKRT9-R163W) were then transfected into HaCaT cells. The small interfering RNAs targeting the KRT9 R163W mutant and wildtype KRT9 were transfected into HaCaT cells, and total RNA isolated at 72 h post-transfection. Quantitative polymerase chain reaction and western blotting were used to analyse the effects of knock-down on KRT9 mRNA and protein levels, respectively. siRNA was shown to specifically inhibit mutant KRT9 mRNA and protein expression (p < 0.01, with 95% confidence limits). Our study suggests that KRT9 is a causal gene for EPPK. This information is helpful for understanding the pathogenesis of EPPK in the Uygur population and raises the possibility of designing a novel siRNA treatment strategy for this population of EPPK patients.

[Effect of rapamycin and dexamethasone on differentiation and maturation of murine bone marrow-derived dendritic cells].

AIM: To observe the effect of rapamycin (Rap) and dexamethasone (Dex) on differentiation and development of murine bone marrow-derived dendritic cells (DC) in vitro. METHODS: DC cells generated from C57BL/6 murine bone marrow cells were induced by GM-CSF and IL-4. During the course, Rap or Dex was added to the culture and the cells were then stimulated by LPS. (1)Morphology development of DCs was observed by inverted microscope and scanning electron microscope.(2)The cells were analyzed by flow cytometry (FCM) to determine the proportion of CD11c(+) cells and the change of CD86 and MHC class II molecule.(3)The influence of DCs treated by Rap or Dex on the allogeneic T cell proliferation was studied by one-way MLR. RESULTS: (1)The morphology of DCs maintained in a durable state of immaturity after Rap or Dex pretreatment.(2)The expression of CD11c and MHC-II slightly decreased but CD86 dramatically reduced on Rap-treated DC cells. There was close relationship between the expression of CD11c on Dex-treated cells and the dosage of Dex. The surface expression of CD86 and MHC-II dramatically reduced on Dex-treated DCs. Moreover, DCs treated by Rap or Dex were both able to resist the maturation triggered by LPS.(3)Bone marrow-derived DCs cultured with Dex or Rap had a lower stimulatory effect on allogeneic T cells compared with that of mature DCs. CONCLUSION: Rap and Dex could keep DCs in durable immaturity. Compared with Dex, which inhibited the expression of co-stimulatory molecules, Rap hardly influenced the differentiation of DCs and the expression of MHC class II molecules.