Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.

The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter-epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell-like properties in gastric cancer (GC) cells infected with CagA-positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self-renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs-like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA-positive GC cells infected with H. pylori exhibit CSCs-like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA-dependent manner, and our findings suggest that this activation is associated with the CSCs-like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA-dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.

A meta-analysis of the prognostic impact of tissue golgi protein 73 (tGP73) in hepatocellular carcinoma.

INTRODUCTION: To date, an increasing number of studies have revealed that GP73 may have prognostic value in liver cancer. However, most of the studies evaluated serum GP73, and the results regarding the prognostic value of tGP73 in liver cancer are still controversial. Therefore, in this meta-analysis, we aimed to determine whether tGP73 has any prognostic value in patients with HCC. MATERIALS AND METHODS: Relevant publications were searched for in PubMed, EMBASE, OVID, the Cochrane Library, and the Web of Science databases up to March 2023. The hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence intervals (95% CIs) of eligible studies were assessed by fixed-effects or random-effects models. In addition, subgroup analyses were conducted to investigate the possible causes of heterogeneity, and publication bias analysis was also performed to assess the reliability of the meta-analysis results. RESULTS: A total of 10 studies were included. These studies included 1569 HCC patients, and a meta-analysis was performed. The results of our meta-analysis showed that higher GP73 expression levels were significantly associated with poorer OS (HR = 1.87, 95% CI: 1.41-2.48, P < 0.0001, I2 = 58%). However, there was no significant correlation between high GP73 expression and disease-free survival (DFS) (HR: 1.43, 95% CI: 0.93-2.33, P = 0.100). In addition, abnormal GP73 expression was also related to higher tumour tissue differentiation grade (OR = 3.03, 95% CI = 2.01-4.57, P < 0.0001, I2 = 89%), later tumour stage (OR = 5.89, 95% CI = 2.31-14.99, P < 0.0001, I2 = 0%), vascular invasion (OR = 1.72, 95% CI = 1.12-2.64, P = 0.010, I2 = 0%), multiple tumours (OR = 2.44, 95% CI = 1.37-3.68, P = 0.001, I2 = 44%) and early postoperative tumour recurrence (OR = 1.92, 95% CI = 1.10-3.28, P = 0.020, I2 = 62%). CONCLUSIONS: The meta-analysis showed that the overexpression of GP73 may be related to a poor prognosis of HCC, and it may also have a predictive effect on the invasion and metastasis of HCC.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer.

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.

Eph and ephrin signaling in the development of the central auditory system.

Acoustic communication relies crucially on accurate interpretation of information about the intensity, frequency, timing, and location of diverse sound stimuli in the environment. To meet this demand, neurons along different levels of the auditory system form precisely organized neural circuits. The assembly of these precise circuits requires tight regulation and coordination of multiple developmental processes. Several groups of axon guidance molecules have proven critical in controlling these processes. Among them, the family of Eph receptors and their ephrin ligands emerge as one group of key players. They mediate diverse functions at multiple levels of the auditory pathway, including axon guidance and targeting, topographic map formation, as well as cell migration and tissue pattern formation. Here, we review our current knowledge of how Eph and ephrin molecules regulate different processes in the development and maturation of central auditory circuits.

Isolated pancreatic injury caused by abdominal massage: A case report.

BACKGROUND: Regular abdominal massage can be used to treat digestive symptoms such as bloating and constipation and is reported to reduce abdominal discomfort, improve digestive function, and increase the quality of life, without serious adverse effects. Isolated pancreatic injury is rare, and most often occurs during severe trauma such as steering wheel impact injury. To our knowledge, pancreatic injury caused by massage has not yet been reported in the literature. CASE SUMMARY: A 57-year-old woman was referred to our hospital for acute abdominal pain and transient syncope. On examination, she had low hemoglobin concentration and a high white blood cell count and neutrophil percentage. Plain computed tomography of the abdomen revealed a substantial hemorrhage in the abdominal cavity. A large amount of exudate in the pancreatic area was considered a hematoma. Preoperative diagnosis was difficult. Her hemoglobin and blood pressure did not rise even after blood. We suspected progressive bleeding in the abdominal cavity and urgently performed exploratory laparotomy. During the operation, the pancreas was confirmed to be ruptured; hence, spleen-preserving pancreatic body and tail resection were performed. A pancreatic fistula was found on the 15th d after the operation, and the patient was discharged with a drainage tube on the 24th d after active treatment. Subsequently, it was discovered that the patient had undergone a vigorous abdominal massage the day before the abdominal pain began. To our knowledge, this is the first report of isolated pancreatic injury and massive abdominal hemorrhage caused by abdominal massage. CONCLUSION: Our findings indicate that any action that increases intra-abdominal pressure may cause internal organ damage. We also review similar cases reported in the literature.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1.

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Primary hepatic neuroendocrine tumour with multiple liver metastases: A case report with literature review.

INTRODUCTION AND IMPORTANCE: To describe an unusual case with a primary hepatic neuroendocrine tumour (PHNET) with multiple liver metastases. CASE PRESENTATION: We reported a 65-year-old woman with PHNET with multiple liver metastases. She was highly suspected of having primary liver cancer with multiple intrahepatic metastases before liver biopsy, but was diagnosed with PHNET with multiple liver metastases after histopathology and immunohistochemistry (IHC) examinations. The patient successfully underwent three times of transcatheter arterial chemoembolization (TACE), and is currently living in a good state without related complications. CLINICAL DISCUSSION: Neuroendocrine tumors (NETs), also known as carcinoids or argyrophilic tumors, are very rare malignant tumors. The liver is the main metastasis site of NETs, but primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Histopathology and immunohistochemistry (IHC) examinations are still the main methods used for diagnosing NETs. There are no treatment guidelines for PHNETs, and surgical resection is generally the preferred treatment. For PHNET patients who are not suitable for surgery, TACE has been proven to be an effective alternative treatment that can effectively reduce the tumour burden and relieve symptoms, but the current evidence is still limited. CONCLUSION: The clinical diagnosis of PHNET still faces great challenges, imaging examinations often lead to misdiagnosis, and its diagnosis mainly depends on histopathology and immunohistochemical examinations. For PHNET patients who are not suitable for surgery, TACE may be an effective alternative therapy.

Research status on immunotherapy trials of gastric cancer.

The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.

Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem.

Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin-A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin-A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage-dependent manner. In mice lacking ephrin-A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin-A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.

Upregulation of NFKBIZ affects bladder cancer progression via the PTEN/PI3K/Akt signaling pathway.

NF­κB inhibitor ζ (NFKBIZ), a member of the IκB family that interacts with NF­κB, has been reported to be an important regulator of inflammation, cell proliferation and survival. However, the role of NFKBIZ in bladder cancer (BC) remains unknown. The present study aimed to investigate the functions of NFKBIZ in BC. First, the expression levels of NFKBIZ and the associations between NFKBIZ expression and the clinical survival of patients were determined using BC tissue samples, BC cell lines and datasets from different databases. Two BC cell lines (T24 and 5637) were selected to overexpress NFKBIZ, and the proliferative, migratory and invasive abilities of cells were determined; additionally, tumor growth following transplantation in in vivo mouse models was analyzed using T24 cells overexpressing NFKBIZ. Subsequently, the association between NFKBIZ and PTEN was determined using data from databases and immunohistochemistry analysis of clinical and nude mice tumor tissues. Finally, the interactions between NFKBIZ, PTEN and the downstream PI3K/AKT/mTOR signaling pathway were evaluated using western blotting. In conclusion, the present results indicated that NFKBIZ expression was low in BC, and NFKBIZ inhibited the proliferation of BC cells through the PTEN/PI3K/Akt signaling pathway, suggesting that NFKBIZ may represent a novel prognostic biomarker in BC and may provide a potential therapeutic tumor­associated antigen for BC.

Spatiotemporal Analysis of Cochlear Nucleus Innervation by Spiral Ganglion Neurons that Serve Distinct Regions of the Cochlea.

Cochlear neurons innervate the brainstem cochlear nucleus in a tonotopic fashion according to their sensitivity to different sound frequencies (known as the neuron's characteristic frequency). It is unclear whether these neurons with distinct characteristic frequencies use different strategies to innervate the cochlear nucleus. Here, we use genetic approaches to differentially label spiral ganglion neurons (SGNs) and their auditory nerve fibers (ANFs) that relay different characteristic frequencies in mice. We found that SGN populations that supply distinct regions of the cochlea employ different cellular strategies to target and innervate neurons in the cochlear nucleus during tonotopic map formation. ANFs that will exhibit high-characteristic frequencies initially overshoot and sample a large area of targets before refining their connections to correct targets, while fibers that will exhibit low-characteristic frequencies are more accurate in initial targeting and undergo minimal target sampling. Moreover, similar to their peripheral projections, the central projections of ANFs show a gradient of development along the tonotopic axis, with outgrowth and branching of prospective high-frequency ANFs initiated about two days earlier than those of prospective low-frequency ANFs. The processes of synaptogenesis are similar between high- and low-frequency ANFs, but a higher proportion of low-frequency ANFs form smaller endbulb synaptic endings. These observations reveal the diversity of cellular mechanisms that auditory neurons that will become functionally distinct use to innervate their targets during tonotopic map formation.

Endoscopic or laparoscopic resection for small gastrointestinal stromal tumors: a cumulative meta-analysis.

BACKGROUND: Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS: A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS: In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

Relationships between neuronal birthdates and tonotopic positions in the mouse cochlear nucleus.

Tonotopy is a key anatomical feature of the vertebrate auditory system, but little is known about the mechanisms underlying its development. Since date of birth of a neuron correlates with tonotopic position in the cochlea, we investigated if it also correlates with tonotopic position in the cochlear nucleus (CN). In the cochlea, spiral ganglion neurons are organized in a basal to apical progression along the length of the cochlea based on birthdates, with neurons in the base (responding to high-frequency sounds) born early around mouse embryonic day (E) 9.5-10.5, and those in the apex (responding to low-frequency sounds) born late around E12.5-13.5. Using a low-dose thymidine analog incorporation assay, we examine whether CN neurons are arranged in a spatial gradient according to their birthdates. Most CN neurons are born between E10.5 and E13.5, with a peak at E12.5. A second wave of neuron birth was observed in the dorsal cochlear nucleus (DCN) beginning on E14.5 and lasts until E18.5. Large excitatory neurons were born in the first wave, and small local circuit neurons were born in the second. No spatial gradient of cell birth was observed in the DCN. In contrast, neurons in the anteroventral cochlear nucleus (AVCN) were found to be arranged in a dorsal to ventral progression according to their birthdates, which are aligned with the tonotopic axis. Most of these AVCN neurons are endbulb-innervated bushy cells. The correlation between birthdate and tonotopic position suggests testable mechanisms for specification of tonotopic position.

Autophagy may play an important role in varicocele.

The present study aimed to determine the expression of autophagy and investigate whether the hypoxia­inducible factor 1α (HIF­1α)/BCL2 interacting protein (BNIP3)/Beclin­1 autophagy signaling pathway serves an important role in activating autophagy in varicocele (VC) rat testes cells. Furthermore, the current study aimed to explain the possible association between autophagy and apoptosis. A total of 48 adult male Sprague Dawley rats were divided into group A (control), group B (VC 15­day), group C (VC 30­day) and group D (VC 45­day), with 12 rats in each group. The rats in group A did not receive any interventions, and in groups B, C, and D the VC model was established simultaneously. At 0, 15, 30, and 45 days, an orchidectomy on the left testes was performed in groups A­D, each on its respective day. Transmission electron microscopy was used to investigate the expression of autophagy. Compared with groups A and B, it was demonstrated that the expression of autophagy in groups C, and D was significantly increased. Hematoxylin and eosin staining revealed that as the rats survived VC longer, the testicular tissue damage became more serious. Furthermore, the Johnson score revealed that VC impaired the spermeiogenesis function of the male rats. Additionally, it was demonstrated that the apoptosis index of the semini-ferous epithelia cells in VC rat testes increased over time, as measured using TUNEL staining. Immunohistochemical analysis revealed that as the VC was prolonged, the expression of HIF­1α gradually increased while the expression of (apoptosis regulator Bcl­2) Bcl­2 gradually decreased. Furthermore, western blot analysis revealed that the protein expression of Bcl­2 decreased and apoptosis regulator Bax increased. Furthermore, HIF­1α, BNIP3, Beclin1 and microtubule associated protein 1 light chain 3 α (LC3)II/LC3I expression gradually increased. However, significant increases in Beclin 1 and LC3II/LC3I were only observed between the day 0 and day 30 groups. In addition, the expression of p62 significantly increased between day 0 and day 15, but gradually decreased between day 15 and day 45. The results of the present study revealed that VC can lead to testicular tissue hypoxia, and that the HIF­1α/BNIP3/Beclin1 autophagy signaling pathway may upregulate autophagy in VC rats testes. Thus, the association between autophagy and apoptosis may serve an important role in male infertility caused by VC.

A novel technique of inserting pancreaticogastrostomy with duct-to-mucosa anastomosis can potentially reduce postoperative pancreatic fistula.

BACKGROUND: We describe our novel technique of inserting pancreaticogastrostomy (IPG) after pancreaticoduodenectomy. In our technique, the seromuscular and mucosal layers of the posterior gastric wall are separated to create a mucosal pouch. A duct-to-mucosa anastomosis is performed through a small incision in the mucosal layer. An inner suture at the seromuscular-mucosal margin incorporating the pancreatic parenchyma and an outer suture on the exterior margin of the seromuscular layer to wrap the pouch around the pancreas are placed to complete the IPG. MATERIALS AND METHODS: We examined the clinicopathological features and outcomes of 259 patients who underwent pancreaticoduodenectomy between January 2010 and April 2014. RESULTS: One hundred forty-three (55.2%) patients underwent IPG, while 116 (44.8%) had conventional pancreaticojejunostomy. Most preoperative and intraoperative parameters were comparable. Overall morbidity in the IPG group was 28.7%. The rate of grade A postoperative pancreatic fistula (POPF) was 7.0%, and the rates of grade B and C POPF were 0.7% and 0.0%, respectively. The corresponding rates of grade A, B, and C fistulae were 5.2%, 8.6%, and 5.2%, respectively. CONCLUSIONS: In selected patients, our novel technique can be performed safely and may reduce the rates of POPF.

The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet ß-cells.

Analysis of MafB(-/-) mice has suggested that the MAFB transcription factor was essential to islet α- and ß-cell formation during development, although the postnatal physiological impact could not be studied here because these mutants died due to problems in neural development. Pancreas-wide mutant mice were generated to compare the postnatal significance of MafB (MafB(Δpanc)) and MafA/B (MafAB(Δpanc)) with deficiencies associated with the related ß-cell-enriched MafA mutant (MafA(Δpanc)). Insulin(+) cell production and ß-cell activity were merely delayed in MafB(Δpanc) islets until MafA was comprehensively expressed in this cell population. We propose that MafA compensates for the absence of MafB in MafB(Δpanc) mice, which is supported by the death of MafAB(Δpanc) mice soon after birth from hyperglycemia. However, glucose-induced glucagon secretion was compromised in adult MafB(Δpanc) islet α-cells. Based upon these results, we conclude that MafB is only essential to islet α-cell activity and not ß-cell. Interestingly, a notable difference between mice and humans is that MAFB is coexpressed with MAFA in adult human islet ß-cells. Here, we show that nonhuman primate (NHP) islet α- and ß-cells also produce MAFB, implying that MAFB represents a unique signature and likely important regulator of the primate islet ß-cell.

Hepatectomy with primary closure of common bile duct for hepatolithiasis combined with choledocholithiasis.

AIM: To evaluate the feasibility of hepatectomy and primary closure of common bile duct for intrahepatic and extrahepatic calculi. METHODS: From January 2008 to May 2013, anatomic hepatectomy followed by biliary tract exploration without biliary drainage (non-drainage group) was performed in 43 patients with intrahepatic and extrahepatic calculi. After hepatectomy, flexible choledochoscopy was used to extract residual stones and observe the intrahepatic bile duct and common bile duct (CBD) for determination of biliary stricture and dilatation. Function of the sphincter of Oddi was determined by manometry of the CBD. Primary closure of the CBD without T-tube drainage or bilioenteric anastomosis was performed when there was no biliary stricture or sphincter of Oddi dysfunction. Dexamethasone and anisodamine were intravenously injected 2-3 d after surgery to prevent postoperative retrograde infection due to intraoperative bile duct irrigation, and to maintain relaxation of the sphincter of Oddi, respectively. During the same period, anatomic hepatectomy followed by biliary tract exploration with biliary drainage (drainage group) was performed in 48 patients as the control group. Postoperative complications and hospital stay were compared between the two groups. RESULTS: There was no operative mortality in either group of patients. Compared to intrahepatic and extrabiliary drainage, hepatectomy with primary closure of the CBD (non-drainage) did not increase the incidence of complications, including residual stones, bile leakage, pancreatitis and cholangitis (P > 0.05). Postoperative hospital stay and costs were nevertheless significantly less in the non-drainage group than in the drainage group. The median postoperative hospital stay was shorter in the non-drainage group than in the drainage group (11.2 ± 2.8 d vs 15.4 ± 2.1 d, P = 0.000). The average postoperative cost of treatment was lower in the non-drainage group than in the drainage group (29325.6 ± 5668.2 yuan vs 32933.3 ± 6235.1 yuan, P = 0.005). CONCLUSION: Hepatectomy followed by choledochoendoscopic stone extraction without biliary drainage is a safe and effective treatment of hepatolithiasis combined with choledocholithiasis.

Morphological and physiological development of auditory synapses.

Acoustic communication requires gathering, transforming, and interpreting diverse sound cues. To achieve this, all the spatial and temporal features of complex sound stimuli must be captured in the firing patterns of the primary sensory neurons and then accurately transmitted along auditory pathways for additional processing. The mammalian auditory system relies on several synapses with unique properties in order to meet this task: the auditory ribbon synapses, the endbulb of Held, and the calyx of Held. Each of these synapses develops morphological and electrophysiological characteristics that enable the remarkably precise signal transmission necessary for conveying the miniscule differences in timing that underly sound localization. In this article, we review the current knowledge of how these synapses develop and mature to acquire the specialized features necessary for the sense of hearing.

A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.

Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001.