[A comparative study of a two-stage surgical approach combining coronectomy with microimplant anchorage traction for extraction of impacted mandibular third molars with different traction angles].

Objective: To establish a two-stage surgical procedure of impacted mandibular third molars (IMTMs) extractions assisted by coronectomy and microimplant anchorage traction and to investigate the influencing factors of root movement and the effects of different traction angles on the clinical outcomes. Methods: Fifty-three IMTM in contact with inferior alveolar nerve (IAN) that underwent tooth extraction in the Peking University School of Stomatology from January 2022 to June 2023 were included, with coronectomy and microimplant anchorage implantation in the first stage of the surgery, root traction was achieved with orthodontic elastic and microimplant anchorages by about 600 g of force, when the IMTM root was detached from IAN, a second surgery was performed to extract the residual root. The basic information of patients and M3M, data on the microimplant anchorage implantation and traction, imaging measurements, and complications were recorded and analyzed. Results: The movement distance of the residual roots was (1.80±0.92) mm, and the duration of traction was (32.9±7.9) d. Multiple linear regression analysis showed that the residual root movement distance was significantly correlated with age, gender, number of roots, traction angle, and depth of the distal bone defect of the second molar (P<0.05). The smaller the traction angle, the more significant the movement of the residual roots (P=0.044). In one case (1.9%, 1/53), the patient experienced abnormal sensation in the lower lip 16 days after traction. Conclusions: The two-stage surgical method of combined coronectomy with rapid traction technique to extract the IMTM allows for rapid movement of the residual root and reduces the risk of IAN injury. The efficiency of root movement can be accelerated by appropriately reducing the traction angle during surgery. The traction effect can be predicted based on indicators such as age, gender, number of roots and depth of distal bone defects of second molar.

[Research and exploration of salivary biological markers for hepatitis B-related hepatocellular carcinoma].

Objective: To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods: Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results: 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion: Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.

[Constructions of the scale of difficulty in the extraction of impacted mandibular third molars by using Delphi method].

OBJECTIVE: To evaluate the relevant indicators affecting difficulty in the extraction of impacted mandibular third molars and score difficulty of different operation and risk indicators, so as to build an intuitive and accurate scale to help operators make more accurate analysis and prediction of difficulty before the operation. METHODS: Based on literature and the clinical review, the difficulty indicators of tooth extraction were summarized. Firstly, 10 doctors from Peking University School and Hospital of Stomatology who had been engaged in alveolar surgery for a long time established an expert nominal group, and then rated whether the summarized indicators needed to be retained in the form of face-to-face questionnaires. A level 1 and 2 item frame for evaluating difficulty in the tooth extraction was formed after discussion; Then Delphi method was used to send a questionnaire to 30 experts by e-mail. After two rounds of scoring and modification, the scale of difficulty in the extraction of impacted mandibular third molars was formed. RESULTS: The recycling rate of two rounds of questionnaires was 100.0%, which showed that the experts were very enthusiastic about the study; The authority coefficients (Cr) of the two rounds of Delphi expert consultation were both 0.92, which showed that the results were representative and authoritative. After two rounds of grading and revision, the variable coefficient (CV) decreased and the Kendall's concordance coefficient (W) increased, which were statistically significant: In the first round, the CV was 0.24 and W was 0.56 (P < 0.001), and in the second, the CV was 0.19 and W was 0.72 (P < 0.001), which indicated that there was a good convergence among the expert opinions. Finally, a scale of difficulty in the tooth extraction containing 12 items at level A and 37 items at level B was formed, including operation difficulty indicators, risk difficulty indicators and common difficulty indicators. CONCLUSION: Based on comprehensive literature retrieval, the study has put forward the concept that difficulty in the extraction of impacted mandibular third molars is composed of operation difficulty and risk difficulty. Using Delphi method, the long-term clinical experience and professional knowledge of experts are transformed into quantitative indicators as a scoring scale. The scale has certain representativeness and authority.

Three-dimensional assessment of root migration and rotation patterns after coronectomy: bone-embedded roots versus soft tissue-covered roots.

In this study, a three-dimensional evaluation was performed to explore differences between bone-embedded and soft tissue-covered roots after mandibular third molar (M3M) coronectomy. Patients were recruited according to the results of cone-beam computed tomography, 6 months after coronectomy. Completely bone-embedded M3Ms were assigned to group B, while completely soft tissue-covered M3Ms were assigned to group S. Data were recorded using digital software. A total of 213 M3Ms in 181 patients were investigated, of which 170 were assigned to the two study groups. Age was the primary factor influencing root migration (P<0.001). The smaller the degree of angulation of the M3M, the more likely was the root complex to rotate distally (r=-0.37, P<0.001). The depth of the impacted M3M contributed to the regeneration of new bone (P≤0.008). The length of the root complex (odds ratio 0.82, P=0.048) and distance from the root to the alveolar crest (odds ratio 1.23, P=0.026) were two critical factors influencing whether the root complex was bone-embedded. Ensuring that the length of the root complex is <7.6mm and the distance between the root and alveolar crest is ≥5mm were both found to be critical to the remaining root being completely bone-embedded and thus preventing eruption and the need for secondary surgery.

Inhibition of miR-133b indicates poor prognosis and promotes progression of OSCC via SOX4.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) accounts for the first largest proportion of oral and maxillofacial malignancies worldwide. Increasing studies have indicated that miRNAs are involved in the regulation of various tumors, including OSCC. However, the exact role of miR-133b in OSCC has not been fully elucidated. Here, we aimed to explore the effects of miR-133b on the development and progression of OSCC and its related mechanisms. PATIENTS AND METHODS: Expression of miR-133b in 44 paired OSCC tissues and adjacent normal tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Clinicopathological characteristics were collected from OSCC patients, and the relationship between miR-133b expression and the prognosis of patients was analyzed. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and colony formation assays were employed to measure the proliferation of OSCC cells transfected with miR-133b inhibitors or mimics. Cell invasion and migration were detected using transwell and Matrigel experiments, respectively. Bioinformatics and Western blot were applied to investigate the possible underlying mechanism of miR-133b in OSCC. RESULTS: MiR-133b was lowly expressed in OSCC tissues compared to adjacent normal tissues (p<0.05). Lower expression miR-133b indicated a significantly worse prognosis of OSCC patients (p<0.05). Over-expression of miR-133b reduced the growth and metastasis of SCC9 cells (p<0.05). Transfection of miR-133b inhibitors obviously enhanced the proliferation, migration and invasion of TSC-15 cells (p<0.05). SRY-Box Transcription Factor 4 (SOX4) was verified as a specific target for miR-133b. Up- or down-regulation of miR-133b decreased or increased the protein expression level of SOX4 in OSCC, respectively (p<0.05). CONCLUSIONS: MiR-133b was lowly expressed in OSCC tissues and cell lines. Down-regulation of miR-133b reduced the proliferation, invasion and migration of OSCC cells via regulating SOX4. All our findings suggested that miR-133b could be used as a potential target for the treatment of OSCC.

[Experimental study on the effects of tumor necrosis factor-α monoclonal antibody on autophagy level in allergic rhinitis mice].

Objective: To observe the effect of tumor necrosis factor-α (TNF-α) monoclonal antibody on autophagy in allergic rhinitis (AR) mice. Methods: Thirty six weeks old BALB/c mice were randomly divided by random number table method into five groups: control group, model group (AR group), TNF-α antibody intervention group (AR+TNF-α group), autophagy inhibitor (3-methylindole, 3-NA) intervention group (AR+3-MA group), TNF-α antibody combined with autophagy inducer rapamycin (RAP) intervention group (AR+TNF-α+RAP group), with 6 mice in each group. AR model was established by conventional method, the corresponding reagent was administered before nasal cavity stimulation sensitization and during the whole experiment. Behavioral scores of mice were obtained, blood was collected from the eye socket, and mice in each group were sacrificed to collect nasal mucosa tissue samples. Pathological changes of nasal mucosa were observed by hematoxylin-eosin staining. Expression levels of inflammatory factor and IgE in serum were detected by enzyme-linked immunosorbent assay (ELISA). Expressions of autophagy related indicators microtubule-associated protein-1 light chain-3B (LC3B), Beclin-1, sequestosome1 (p62), autophagy-related 5 (ATG5), autophagy-related 7 (ATG7) were measured by Real-time PCR and Western blot. The aggregation of LC3B protein was observed by immunofluorescence. SPSS 19.0 software was used for statistical analysis. Results: Compared with the AR model group, symptoms of AR in AR+TNF-α group and AR+3-MA group were mild; the pathological changes of nasal mucosa were weak; the expression of IgE, TNF-α, interleukin 4 (IL-4), interferon-γ (IFN-γ) in serum significantly reduced (IgE: 666.19±78.35 (x±s) vs. 692.38±64.29 vs. 1 059.05±146.44, TNF-α: 112.06±12.95 vs. 113.17±15.43 vs. 161.22±17.96, IL-4: 54.05±7.14 vs. 58.26±5.67 vs. 79.95±6.33, IFN-γ: 28.58±4.51 vs. 30.67±2.60 vs. 39.83±3.31, all P<0.05), and the expression of LC3B Ⅱ/Ⅰ, Beclin-1, ATG5, ATG7 in nasal mucosa significantly decreased, the expression of p62 significantly elevated. After intervention with autophagy inducer RAP, the therapeutic effect of TNF-α monoclonal antibodies on AR was antagonized. Conclusion: TNF-α monoclonal antibody significantly improves nasal symptoms in AR mice by inhibiting autophagy levels.

The complete genomic sequence of Sugarcane mosaic virus from Canna spp. in China.

BACKGROUND: Sugarcane mosaic virus (SCMV) is the prevalent virus inducing maize dwarf mosaic and sugarcane mosaic diseases in China. According to the phylogenetic results of the complete genomic and coat protein gene sequences, SCMV was divided into four or five molecular groups, respectively. Previously, we detected SCMV isolates of group SO from Canna spp. in Ji'nan, Shandong province, China. FINDINGS: In this study, we collected two SCMV isolates infecting Canna spp. in Ji'nan (Canna-Ji'nan) and Tai'an (Canna-Tai'an) of Shandong, China. Their complete genome sequences had genome of 9576 nucleotides and contained a large open reading frame encoding a polyprotein of 3063 amino acids. The phylogenetic analysis showed that the both Canna-Ji'nan and Canna-Tai'an were clustered into an independent group based on the complete genome sequence. CONCLUSION: In this study, we report the complete genome sequences of SCMV infecting Canna spp. from Ji'nan and Tai'an. This is the first report on SCMV belonging to SO group.

[Timeless promotes the proliferation of hepatocellular carcinoma cell by reprogramming of glucose metabolism].

Objective: To explore the function and molecular mechanism of Timeless in promoting hepatocellular carcinoma (HCC) growth. Methods: The expression of Timeless in HCC and paracancer tissues were analyzed by using the public data of HCC. Timeless was overexpressed in MHCC97L cells and silenced in MHCC97H cells, respectively, and the expression of Timeless and its downstream molecules were detected by real-time PCR and western blot. The effects of Timeless on cell glycolysis, oxidative phosphorylation and proliferation were detected by the glucose uptake experiment, lactic acid detection experiment, the extracellular fluid pH detection experiment, cell oxygen consumption test and cell viability assay, respectively. Results: The level of Timeless in HCC tissue was significantly higher than that of paracancer tissue (P<0.05). The relative cellular glucose uptake levels in the groups of Timeless knockdown, including siTimeless-1 and siTimeless-2 group were 0.510±0.119 and 0.508±0.099, respectively, significantly different from that of control group (P<0.05); The relative cellular uptake level of Timeless overexpressed group was 1.953±0.324, significantly different from that of vector transfected group (P<0.05). The relative levels of lactic acid production in the siTimeless-1 and siTimeless-2 group were 0.579±0.096 and 0.550±0.120, respectively, significantly different from that of control group (P<0.05); The relative production level of lactic acid in the Timeless overexpressed group was 1.463±0.179, significantly different that of vector transfected group (P<0.05). The extracellular pH values of siTimeless-1 and siTimeless-2 group were 7.390±0.035 and 7.370±0.060, respectively, significantly different from that of control group (P<0.05); the extracellular pH value of Timeless overexpressed group was 7.130±0.031, significantly different than vector transfected group (P<0.05). Oxygen consumption rate of siTimeless-1 and siTimeless-2 group were 3.686±0.389 and 3.955±0.431, respectively, significantly higher than 1.690±0.297 of control group (P<0.05); Oxygen consumption rate of Timeless overexpressed group was 1.302±0.336, significantly lower than 3.185±0.262 of vector transfected group (P<0.05) Timeless inhibited the expression of p53. The cell glucose uptake, lactic acid production, the pH of extracellular culture medium and cell oxygen consumption of control group were not significantly different from that of Timeless and p53 co-silenced group [(si-Timeless+sip53) group] (P>0.05); the glucose uptake, the production of lactic acid, the pH of the extracellular culture medium and the oxygen consumption of Timeless co-transfected with p53 (Timeless+p53) group were not significantly different from those of vector transfected group (P>0.05). Timeless promoted the proliferation of HCC cells through inhibiting the expression of p53. Conclusion: Timeless promotes reprogramming of glucose metabolism and proliferation of HCC cells by inhibiting the p53-dependent signaling pathway.

[LincRNA-ROR functions as a ceRNA to regulate Oct4, Sox2, and Nanog expression by sponging miR-145 and its effect on biologic characteristics of colonic cancer stem cells].

Objective: To investigate the impact of lincRNA-ROR, a ceRNA by binding miR-145 on the expression of the downstream genes Oct4, Sox2 and Nanog, and related biological characteristics of colon cancer stem cells, and to elucidate the clinical significance of this molecular regulatory network. Methods: Fifty-two cases of colorectal cancer tissue and adjacent tissue were collected at Nanyang City Central Hospital and Nanyang Second Hospital, Henan Province, from 2014 to 2016. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of lincRNA-ROR and miR-145 in colorectal cancer tissue and isolated colon cancer cells. The correlation between the expression of lincRNA-ROR, miR-145 and the clinicopathologic features of colon cancer was performed. CD44(-)CD133(-) and CD44(+) CD133(+) cells were isolated from SW1116 by using flow cytometry. The expression of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR and miR-145 in cells were detected by qPCR. The relationship between lincRNA-ROR, miR-145, Oct4, Sox2 and Nanog was analyzed by bioinformatics, dual luciferase reporter assay, qPCR and Western blot. The effects of silencing lincRNA-ROR on the proliferation and chemosensitivity of colon cancer stem cells were detected by MTT, colony formation. Results: LincRNA-ROR was frequently up-regulated and inversely correlated with miR-145 down-regulation in the colon cancer specimens(P<0.05). LincRNA-ROR was related to tumor size, lymph node involvement and distant metastasis(P<0.05), and miR-145 was found related to tumor size and tumor location(P<0.05). CD44(+) CD133(+) cells were successfully isolated from SW1116 by flow cytometry. The levels of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR in CD44(+) CD133(+) cells were significantly increased, while miR-145 was decreased compared with CD44(-)CD133(-)cells(P<0.05). The levels of CD44, CD133, lnc-ROR in CD44(+) CD133(+) cells were significantly reduced upon cell adherence, while miR-145 was significantly increased(P<0.05). Bioinformatics analysis revealed that lincRNA-ROR shared miRNA response elements with core transcription factors Oct4, Sox2 and Nanog. MiR-145 significantly inhibited the expression of lincRNA-ROR, Oct4, Sox2 and Nanog. Silencing lincRNA-ROR significantly inhibited colon cancer stem cells proliferation and increased the sensitivity to chemotherapy. Conclusions: Linc-ROR functions as a key ceRNA to prevent core TFs, e. g., Oct4, Sox2, Nanog, from miR-145-mediated suppression in colon cancer stem cells and regulates cell proliferation and chemosensitivity.The data may provide insights into the pathophysiological interactions of the components of genetic networks in the development of colon cancer and may lead to new therapies in the future.

Methylmercury-l-Cysteine targeting L-type amino acid transporter conjugate cytotoxicity on C6 glioma cells.

Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma. MeHg-L-cys enhanced the ability of targeting glioma cells and reduced the adverse reactions to normal brain tissues. Therefore, it is significantly important to develop new anti-glioma drugs targeting the blood-brain barrier.

Primary chordoma in the nasal cavity and nasopharynx: CT and MR imaging findings.

BACKGROUND AND PURPOSE: Primary chordoma in the nasal cavity and nasopharynx is an extremely rare tumor in the extraosseous axial skeleton. Unlike intracranial chordomas, lesions in these sites primarily present as a soft tissue mass without involvement of the skull base bone (clivus), so the preoperative diagnosis of the tumor is possibly difficult. Here, we reviewed the imaging features of 5 cases of chordomas in the nasal cavity and nasopharynx that resulted in successful diagnosis and differential diagnosis of this rare tumor. MATERIALS AND METHODS: We retrospectively studied 5 patients with histologically proven chordomas in the nasal cavity and nasopharynx. The lesion features of CT and MR imaging were reviewed, with emphasis on the size, shape, location, margin, calcification, CT attenuation characteristics, signal intensity, and degree of MR imaging enhancement. RESULTS: Expansible and lobular soft tissue masses were mainly present, with irregular intratumor calcification in all 5 cases on CT examination. MR imaging revealed a well-defined tumor with heterogeneous signal intensity in 4 patients, whereas homogeneous signal intensity in 1 patient was present on all pulse sequences. Four cases of nasopharyngeal mass showed mild to moderate heterogenous enhancement. Intratumor septa could be seen in 2 cases. CONCLUSIONS: Although no imaging features are pathognomonic, primary chordomas without skull base (clivus) bony changes in the nasal cavity and nasopharynx have some CT and MR imaging findings that are suggestive of diagnosis. The differential diagnosis of the soft tissue mass should be limited to these sites.

Management of diaphragmatic rupture from blunt trauma.

INTRODUCTION: Diagnosis of diaphragmatic rupture is difficult, and delays could result in a catastrophic outcome. We reviewed our institution's management of patients with diaphragmatic rupture after blunt trauma. METHODS: All patients in this study were treated at Tan Tock Seng Hospital, Singapore, from March 2002 to October 2008. Patients with penetrating injuries were excluded. The parameters included age, mechanism of injury, haemodynamic status at admission, Glasgow coma scale (GCS) score, injury severity score (ISS), imaging studies, location of diaphragmatic injuries, associated injuries and outcome. RESULTS: 14 patients with a median age of 38 years formed the study group. Vehicular-related incidents accounted for 71.4 percent of the injuries. The median GCS score on admission was 14 (range 3-15), while the median systolic blood pressure and heart rate were 94 (range 50-164) mmHg and 110 (range 76-140) beats per minute, respectively. The median ISS was 41 (range 14-66). All had chest radiographs performed in the emergency department, six (42.9 percent) had computed tomography performed before surgery, while the remaining eight (57.1 percent) were sent straight to the operating theatre from the emergency department. There were five (35.7 percent) right-sided and nine (64.3 percent) left-sided diaphragmatic ruptures. The mortality rate was 35.7 percent. Some of the associated injuries included eight (57.1 percent) splenic lacerations, five (35.7 percent) haemothorax and lung injuries, four (28.6 percent) bone fractures and three (21.4 percent) liver lacerations. 12 (85.7 percent) patients underwent repair of the diaphragmatic rupture using interrupted polypropylene suture, while the remaining two (14.3 percent) were too haemodynamically unstable to undergo definitive treatment. Advanced age, haemodynamic instability and raised ISS were associated with mortality. CONCLUSION: An accurate diagnosis of diaphragmatic rupture in trauma patients is difficult, and a thorough examination of both the hemidiaphragms is mandatory during emergency laparotomy for these patients. Those with more severe injuries and decreased physiological reserves usually fare worse.

Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers' syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence.

Patients with Peutz-Jeghers' syndrome (PJS) develop hamartomatous gastrointestinal polyps and characteristic pigmentation, as a result of germline mutations in the LKB1 gene. The hamartomas in PJS were long considered to be without malignant potential. There is, however, accumulating epidemiological evidence to suggest that PJS predisposes to cancers at several different sites (colon, pancreas, breast, ovary, testis, and cervix), although large enough patient samples are rarely available to prove this. Allelic imbalance [allele loss, loss of heterozygosity (LOH)] has previously been reported in a small number of PJS polyps, suggesting that LKB1 acts as a tumour suppressor in these tumours. This study confirms allelic loss at LKB1 in PJS polyps and shows that LOH also occurs in cancers of the colon, breast, and cervix in PJS patients. Allele loss was additionally found in a colonic adenoma from a PJS patient, strongly suggesting the existence of a hamartoma-(adenoma)-carcinoma sequence in tumourigenesis. These results provide molecular evidence that PJS patients are predisposed to cancers at several sites, as a direct result of selection for loss of the 'wild-type' LKB1 allele in tumours. Given the rare involvement of LKB1 in sporadic cancers, these data also suggest that the indirect effect on cancer risk (or 'bystander effect') proposed for hamartomas in juvenile polyposis does not apply to carcinomas in PJS.

Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours.

Germline mutations in the LKB1 (STK11) gene (chromosome sub-band 19p13.3) cause characteristic hamartomas and pigmentation to develop in patients with Peutz-Jeghers syndrome. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population and Peutz-Jeghers patients are at increased risk of benign and malignant ovarian tumours, particularly granulosa cell tumours. Loss of heterozygosity (allele loss, LOH) has been reported in about 50% of ovarian cancers on 19p13.3. LKB1 is therefore a candidate tumour suppressor gene for sporadic ovarian tumours. We found allele loss at the marker D19S886 (19p13.3) in 12 of 49 (24%) sporadic ovarian adenocarcinomas. Using SSCP analysis, we screened ten ovarian cancers with LOH, 35 other ovarian cancers and 12 granulosa cell tumours of the ovary for somatic mutations in LKB1. No variants were detected in any of the adenocarcinomas. Two mutations were detected in one of the granulosa cell tumours: a mis-sense mutation affecting the putative 'start' codon (ATG --> ACG, M1T); and a silent change in exon 7 (CTT --> CTA, leucine). Like BRCA1 and BRCA2, therefore, it appears that LKB1 mutations can cause ovarian tumours when present in the germline, but occur rarely in the soma. The allele loss on 19p13.3 in ovarian cancers almost certainly targets a different gene from LKB1.

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.

Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts.

Platelet activating factor-induced changes in gastric motility and vascular resistance.

Our study evaluated the hypothesis that gastric contractions may contribute to ischemia by increasing vascular resistance. Using an ex vivo segment of the dog's stomach as the experimental model, contractions were induced with platelet activating factor (PAF) and bethanechol, a cholinergic vasodilator. Spontaneous contractions produced slight increases in luminal pressure and corresponding increases in vascular resistance. PAF caused statistically significant, dose-dependent increases in the force of gastric contractions that were highly correlated with phasic changes in vascular resistance. To ensure that the relationship between contractions and vascular resistance was independent of vascular tone, we next examined responses to bethanechol. Bethanechol stimulated contractions that also transiently increased both luminal pressure and vascular resistance. Our results demonstrate that gastric contractions markedly increase vascular resistance and support the hypothesis that hypercontractility may contribute to the development of mucosal ischemia during ulceration.

[Effect of radix Salviae miltiorrhizae on gastric mucosal barrier].

The authors observed the effects of Radix Salviae Miltiorrhizae (RSM, Dan-shen) on gastric mucosa of twelve dogs with ex vivo gastric chambers. It was demonstrated that in physiological condition RSM increases gastric mucosal blood flow and potential difference, and decreased hydrogen ion back-diffusion. In this way, RSM kept the integrity of mucosal barrier, and improved its defence function. In pathological condition caused by aspirin, however, RSM could only delay the advance of mucosal lesions. According to this observation, RSM may be used as a prophylactic medicine combined with cimetidine in critical ill patients.