Cryptanshinone extract of Salvia miltiorrhiza stimulates pediatric acute myeloid leukemia stem cell apoptosis and the anti-inflammatory mechanism via accelerating microRNA-211-5p to supress Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway activation.

This study was designed to explore cryptanshinone (CPT) extract of Salvia miltiorrhiza stimulating pediatric acute myeloid leukemia (AML) stem cell (LSC) apoptosis and anti-inflammatory mechanism via accelerating microRNA (miR)-211-5p to restrain Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway activation. Obtaining blood samples from pediatric acute myeloid leukemia patients and healthy volunteers and detecting miR-211-5p and JAK2 were performed. Purchase of the human AML cell line KG1a was conducted, and sorting of KG1a cells was to gain LSC. Test of miR-211-5p and JAK2, the phosphorylation of JAK2/STAT3 was implemented. Pretreatment of LSCs was with CPT. Variation of miR-211-5p and JAK2 in LSCs was via plasmid transfection to explore their actions in cell advancement with apoptosis and inflammation. Identification of the targeting of miR-211-5p with JAK2 was implemented. In results: MiR-211-5p was declined in endometrial cancer, while JAK2 was elevated; CPT was available to boost LSC apoptosis and restrain the inflammation; elevated miR-211-5p or repressive JAK2 was available to strengthen the acceleration of CPT on LSCs apoptosis and the repression of inflammation; MiR-211-5p targeted JAK2; augmented JAK2 was available to turn around the action of elevated miR-211-5p. We conclude that CPT extract of Salvia miltiorrhiza stimulated pediatric LSC apoptosis and restrained the inflammation via accelerating microRNA (miR)-211-5p to suppress JAK2/STAT3 pathway activation.

[Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head].

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

[Homosexual behavior and related factors among married men who have sex with men in Mianyang city, Sichuan province].

Objective: To understand the homosexual behavior and related factors among married MSM in Mianyang city. Methods: Between January and October in 2017, a snowball sampling method was adopted to carry out cross-sectional survey through questionnaires plus HIV testing among those MSM in Mianyang city. Logistic regression model was used to analyze homosexual behaviors and related factors among married MSM under study. Statistical analysis was used by EpiData 3.1 and SPSS 19.0 software. Results: A total of 234 MSM participated in this survey. The overall rate of homosexual behavior in these married MSM appeared as 94.9% (222/234). Rate of having anal sex behavior was 94.4% (221/234) in the past 6 months, with rate of condom use as 57.9% (128/221). HIV positive rate was 8.1% (18/222). As for the motives for homosexual behavior after marriage, 87.8% (195/222) were driven by feelings of love, 12.2% (27/222) due to 'releasing pressure'. Proportion of male sex partners would include occasional sex partners (62.2%, 138/222), stable male sex partners (26.1%, 58/222) and stable boyfriends (11.7%, 26/222). Factors from logistic regression analysis showed that homosexual behaviors were related to the factors including education level of senior high school or above vs. education level of junior middle school or below (OR=3.65, 95%CI: 1.33-9.98); local residency over one year vs. the ones having local residency less than one year (OR=23.28, 95%CI:1.67-324.89); having 10 or more friends in the MSM community vs. having below 10 friends in MSM community (OR=4.15, 95%CI: 1.28-13.43); without sex pleasure with spouse vs. having sex pleasure with spouse (OR=3.25, 95%CI: 1.22-8.62); having 2 or more anal sex partners in the past 6 months vs. having less than 2 anal sex partners in the past 6 months (OR=0.28,95%CI: 0.09-0.81). Conclusions: The rate of homosexual behavior and HIV positive rate were high among MSM in Mianyang city. Homosexual behaviors after marriage were influenced by multiple factors among MSM. The motives of homosexual behavior after marriage were driven by feelings of love, the related factors were education level of senior high school or above, local residency over one year, having 10 or more friends in the MSM community and without sex pleasure with spouse. As for the motives of these behaviors was caused by releasing pressure, the related factors was having more than 2 anal sex partners.

[Oral and maxillofacial surgery residency training in the United States: what can we learn].

China is currently in the process of establishing formal residency training programs in oral and maxillofacial surgery and other medical and dental specialties. Regulatory agencies, and educational and academic institutions in China are exploring mechanisms, goals and standards of residency training that meet the needs of the Chinese healthcare system. This article provides an introduction of residency training in oral and maxillofacial surgery in the United States, with emphasis on the accreditation standard by the Commission on Dental Accreditation. As there are fundamental differences in the medical and dental education systems between China and United States, the training standards in the United States may not be entirely applicable in China. A competency-based training model that focus on overall competencies in medical knowledge, clinical skills and values at the time of graduation should be taken into consideration in a Chinese residency training program in oral and maxillofacial surgery.

Study on the relationship between the structure and functions of anti-human cervical cancer single-chain antibody and the lengths of linkers.

BACKGROUND: This study aimed to find the linker with minimal impact among chains to fight against the structure and function of cervical cancer (CC) single-chain antibody. MATERIALS AND METHODS: The original variable region of heavy chain (VH) and variable region of light chain (VL), and the single-chain antibody with linkers of different lengths (n = 1-8) were modeling by homologous modeling, while the peptide chain structure of (Gly4Ser)n was utilized by the linkers. Comparison of the similarity of original VH/VL and VHn/VLn was carried out by applying the algorithm of spatial hierarchical alignment based on the spherical coordinates. The fore and aft distance and diffusion radius of alpha (α) were also calculated. The stability of antibody with different linker length was then compared. ELISA method was adopted to evaluate the immunological activity of single-chain antibody with different linkers. MTT assay was used to analyze the inhibition effect of ScFv-n on CC cells. RESULTS: When n = 4, the structures were the most similar between ScFv and the original VH/VL. When n = 3, the influence of adding connecting peptide on the stability of single-chain antibody was the least. The result of ELISA and MTT methods indicated that when n = 3, single-chain antibody gained the highest activity. CONCLUSION: The optimum length of linker of anti-human CC single-chain antibody was n = 3 from the point of mathematical modeling and biology experiments. This study provided new ideas for the design and constructions of single-chain antibody, and theoretical basis for the treatment of CC.

External Dentin Stimulation Induces ATP Release in Human Teeth.

ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation-dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation-induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation-induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain.

Expression of ecto-ATPase NTPDase2 in human dental pulp.

Dental pulpal nerve fibers express ionotropic adenosine triphosphate (ATP) receptors, suggesting that ATP signaling participates in the process of dental nociception. In this study, we investigated if the principal enzymes responsible for extracellular ATP hydrolysis, namely, nucleoside triphosphate diphosphohydrolases (NTPDases), are present in human dental pulp. Immunohistochemical and immunofluorescence experiments showed that NTPDase2 was predominantly expressed in pulpal nerve bundles, Raschkow's nerve plexus, and in the odontoblast layer. NTPDase2 was expressed in pulpal Schwann cells, with processes accompanying the nerve fibers and projecting into the odontoblast layer. Odontoblasts expressed the gap junction protein, connexin43, which can form transmembrane hemichannels for ATP release. NTPDase2 was localized close to connexin43 within the odontoblast layer. These findings provide evidence for the existence of an apparatus for ATP release and degradation in human dental pulp, consistent with the involvement of ATP signaling in the process of dentin sensitivity and dental pain.

Characterization of cadmium uptake and translocation in a cadmium-sensitive mutant of rice (Oryza sativa L. ssp. japonica).

To understand the physiological mechanism that confers Cd sensitivity/tolerance, Cd uptake and translocation by Cd-sensitive mutant and wild-type rice seedlings were characterized using radioactive tracer. Time-dependent Cd accumulation during 210 min was 1.8-fold higher in roots of the mutant than of wild-type rice. The kinetics of Cd uptake showed that two processes were involved: a first, fast, probably passive process and a second, slower, possibly physiological process. After 96 h, more Cd was translocated to the shoot of mutant compared with wild-type rice. Low temperature (2 degrees C), carbonyl cyanide m-chlorophenylhydrazone, and dicyclohexylcarbodiimide inhibited Cd accumulation to a greater extent in mutant than wild-type rice, suggesting that metabolism plays a more important role in Cd uptake for the rice mutant. Cd uptake into the symplasm is linked to Ca2+ transport, as revealed by the inhibition of Cd accumulation by La and high Ca by equal percentages in both mutant and wild-type rice. Cd uptake and root-to-shoot translocation in the mutant were inhibited more markedly by Zn and Mn than in wild-type rice. This indicates that transport sites other than entry into the root symplasm are also stimulated in the mutant. The results suggest that enhanced absorption into the root and further accumulation in the shoot is one of the mechanisms involved in Cd accumulation and sensitivity, and the difference in Cd uptake and root-to-shoot translocation between mutant and wild-type rice may be mediated partly by energy supply and transporters for Zn and Mn.

[Studies on the recurrent attacks of acute adenolymphangitis due to Malayan filariasis].

OBJECTIVE: To explore the role of filarial and bacterial infections in the recurrent attacks of acute adenolymphangitis due to malayan fialriasis. METHODS: 1. To observe the seasonal fluctuation of acute attacks by performing monthly follow-up on patients with history of acute attacks in recent years. 2. To study the relationship between bacterial infection and filarial adenolymphangitis by performing bacteria culture and anti-streptolysin O test. 3. To investigate the variation of acute attacks by controlling filariasis transmission or by treating patients with a history of recurrent acute attacks. RESULTS: 1. The peak of acute attacks in patients coincided with the peak of vector transmission season. 2. Of the 97 cases examined by bacteria culture, 90 cases were negative; of the 255 cases examined by anti-streptolysin O test, the titres in 94.1% (143/152) of the cases with first attack and simple adenolymphangitis were within normal limits, however, the titres in 27.2% (28/103) of the cases complicated with elephantiasis were increased. 3. The acute attack rate of adenolymphangitis per year reduced significantly in cases with first attack and simple adenolymphangitis after effective control of filariasis transmission. 4. There was no evidence of the reduction of acute attacks by treating patients with DEC alone. CONCLUSION: In malayan filariasis endemic areas, the main causes of recurrent attacks of acute adenolymphangitis might be the repeated filarial infections due to the persistence of filariasis transmission.

Magnetic resonance imaging of the temporomandibular joint: value of pseudodynamic images.

Magnetic resonance fast scanning technique (gradient recalled acquisition at steady state) has been reported to be useful when evaluating the dynamics of the temporomandibular joint and also to be accurate for determining the disk position. Yet in our clinical experience gradient recalled acquisition at steady state images have frequently been inferior to proton density images for diagnosis of temporomandibular joint internal derangement. The first aim of this study was to compare gradient recalled acquisition at steady state images with proton density images for diagnosis of disk position. The second aim was to identify what additional information could be gathered from gradient recalled acquisition at steady state images when compared with static proton density images. We obtained unilateral images from 20 patients with signs and symptoms of temporomandibular joint internal derangement and from 20 asymptomatic volunteers. Multiple gradient recalled acquisition at steady state images were obtained during mouth opening and closing and proton density images were obtained at the closed and open mouth positions. The results showed that the gradient recalled acquisition at steady state images were in accordance with the proton density images in 32 joints (80%) and were false negative in 8 joints (20%). Six of the joints with false-negative gradient recalled acquisition at steady state images showed sideways disk displacement, and two showed partial anterior disk displacement. Gradient recalled acquisition at steady state images, on the other hand, provided information about movement pattern and also demonstrated impingement of the joint structures on the muscles anterior to the joint at maximal mouth opening. It was concluded that gradient recalled acquisition at steady state images cannot replace proton density images for diagnosis of disk position but they can provide supplementary information for evaluation of joint function.

Velopharyngeal incompetence and persistent hypernasality after adenoidectomy in children without palatal defect.

Persistent hypernasal speech after adenoidectomy has been reported in children with palatal deficiency. Hypernasality after adenoidectomy can also occur in children with normal palatal function. The aim of the present study was to identify the cause of velopharyngeal incompetence and hypernasality after adenoidectomy in children who did not have palatal defect as a predisposing factor. Sixteen children who developed hypernasality after adenoidectomy were included in the present study. Standard lateral cephalometry, videofluoroscopy, and nasopharyngoscopy were performed to visualize the velopharynx and its function during speech. The results showed that enlarged tonsils and prominent remaining adenoid tissue on the posterior pharyngeal wall were the causes of hypernasality in these children. Incomplete removal of the adenoid tissue should be avoided and enlarged tonsils should be removed at the time of adenoidectomy to prevent the risk for postoperative hypernasality.

Steepness of the articular eminence in the temporomandibular joint. Tomographic comparison between asymptomatic volunteers with normal disk position and patients with disk displacement.

OBJECTIVE: A steep articular eminence has been proposed as one etiologic factor for the development of TMJ disk displacement. The purpose of this study was to determine the steepness of the articular eminence in asymptomatic volunteers with superior disk position and to compare it with the articular eminence in patients with internal derangement. STUDY DESIGN: We investigated 34 asymptomatic volunteers and 71 patients. The steepness of the articular eminence was determined on sagittally corrected tomograms, and disk position was diagnosed by dual space arthrotomography. RESULTS: The results showed that the articular eminence was on the average steeper in the asymptomatic volunteers in the lateral (64.9 degrees), central (64.4 degrees), and medial (65.4 degrees) sections of the joint than in the patients (56.1 degrees, 60.2 degrees, 58.9 degrees, respectively). When the comparison of the steepness of the eminence was based on the presence or absence of osseous changes in the form of remodeling or osteoarthrosis, no difference was found between the asymptomatic volunteers and the patients with disk displacement but without such changes. The largest difference in the steepness of the eminence was found between the persons with osseous changes and those without. CONCLUSION: These findings contradict earlier studies that have indicated a steep articular eminence to be one etiologic factor for the development of disk displacement. The results of this study showed that the steepness of the articular eminence is decreased in the patients as a result of remodeling or degenerative changes of the bone that are a result of the internal derangement.

Condyle position in the temporomandibular joint. Comparison between asymptomatic volunteers with normal disk position and patients with disk displacement.

Though the significance of condyle-fossa relationship in the temporomandibular joint has not yet been clarified and normal condyle position not yet defined, efforts have been made to guide the mandibular condyle into a centric position in the glenoid fossa with the aim of relieving the symptoms in patients with orofacial pain and temporomandibular joint internal derangement. The present study investigated the mandibular condyle position in 34 joints in asymptomatic volunteers with normal disk position as verified by arthrography and compared it with the mandibular condyle position in 85 joints in patients with different stages of internal derangement. The results showed that in the volunteers with normal joints including normal superior disk position, the condyles were almost randomly distributed in anterior, centric, and posterior positions in the glenoid fossa. Of the joints with anterior disk displacement approximately half of the number of joints with reducing disks and two thirds of the joints with nonreducing disks appeared to have posterior condyle position. Posterior condyle position cannot, however, be used to diagnose internal derangement because the condyle was found to be either in anterior or centric position in many joints with a displaced disk. The variety in condyle position in the healthy joints ought to be taken into consideration if treatment is chosen to normalize the mandibular condyle position by bringing it into a centric position in the glenoid fossa.

Comparison of tongue position during speech before and after pharyngeal flap surgery in hypernasal speakers.

Tongue position was cineradiographically analyzed during speech, before and after pharyngeal flap surgery, in 19 hypernasal cleft palate speakers with acceptable articulation and in 10 noncleft reference individuals. The results showed that the position of the tongue was significantly retracted during production of the consonants (/ti/, /ki/, and /ka/) in the cleft palate speakers with VPI compared to the reference individuals. Following pharyngeal flap surgery, the position of the tongue remained different in cleft palate speakers compared to reference individuals, although the articulation quality and resonance were evaluated to have normalized in almost all the speech samples produced by cleft palate speakers. It was suggested that the cleft palate speakers with VPI may exploit the plasticity of the speech system in order to achieve perceptually good speech, even though their tongue movements might be different from tongue movement in noncleft speakers.

The influence of pharyngeal flap on facial growth. Long-term results in the patients with isolated cleft palate.

The facial growth of 22 children from 6 to 17 years of age with repaired isolated cleft palate was studied. Eleven patients had had posterior pharyngeal flap surgery at about 7 years of age and were examined one year before, and three and 10 years after, flap surgery. The other eleven patients served as matched references. The convexity of the facial profile decreased significantly in both groups. There were differences in growth between the two groups in the variables that concerned mandibular position and anterior facial height. The results indicated that the reference individuals had achieved more anterior growth rotation during the development of the face. There was no improvement in mandibular retrognathism in the flap group until the patients were 10 years of age, but the mandible then resumed the normal anterior rotation and had caught up with the reference group after puberty, to result in a facial form with no significant difference from that in adolescents with cleft palate and without pharyngeal flaps. We suggest that the influence of a pharyngeal flap on facial growth has no long term clinical importance in patients with an isolated cleft palate, but the impact of the temporary change in facial growth after pharyngoplasty should be taken into consideration when orthodontic treatment is planned.

A structure-activity relationship study of batracylin analogues.

A number of isoindolo[1,2-b]quinazolines and some benzo[4,5]isoquinolino[1,2-b]quinazolines as structural modification analogues of the antitumor compound batracylin were synthesized and evaluated against HL-60 cell growth and in topoisomerase II-mediated DNA cleavage assays. Of the compounds studied, 10,12-dihydro-7,8-methylenedioxyisoindolo[1,2-b]quinazolin-1 2(10H)-one (1d), 2-amino-10,12-dihydroisoindolo[1,2-b]quinazolin-12(10H)-one (1p), and 2-amino-7,8-methylenedioxy-10,12-dihydroisoindolo[1,2-b] quinazolin-12(10H)-one (1ab) exhibited good inhibitory activities against HL-60 cell lines as well as induction of topo II-mediated DNA cleavage activities.

A modified palatopharyngeous flap operation and its application in the correction of velopharyngeal incompetence.

The conventional sphincteric pharyngoplasty does not achieve velopharyngeal competence in certain cases because of the intrinsic deficiency of the technique. A modified palatopharyngeous flap operation was introduced and used as a secondary procedure for the correction of velopharyngeal incompetence in 15 cleft palate patients. The results showed that the lateral-to-lateral connection and the high attachment of the palatopharyngeal flaps can form a new velopharyngeal port that is easily closed by velar movement. The surgical result is satisfactory, as revealed by the speech intelligibility test, videofluoroscopy, and nasopharyngoscopy. The surgical technique is described and the importance of presurgical identification of velopharyngeal movements is stressed in this paper.

Interactive influence of a pharyngeal flap and an adenoid on maxillofacial growth in cleft lip and palate patients.

The aim was to evaluate whether a large adenoid, which aids velopharyngeal function, influences facial growth and if a pharyngeal flap reinforces the effect. Forty cleft palate patients were divided into two groups: adenoid and nonadenoid. Twenty of the patients had a pharyngeal flap operation. All the patients had three cephalograms taken at the same ages over a period of 5 years. At an average age of 4.7 years, i.e., one year before any pharyngoplasty, the mandibular inclination was larger in the adenoid group. This inferioposterior mandibular position was aggravated when a flap was added and with age. The present study suggests that the nasopharyngeal space, which is indicative of nasal airway patency, is influenced by a pharyngeal flap as well as an adenoid which, in turn, influences facial growth direction in the cleft palate population. Airway variables ought to be taken into consideration when the growth effect of cleft palate treatment is evaluated.

Facial growth after pharyngeal flap surgery in cleft palate patients: a five-year longitudinal study.

To assess the influence of a pharyngeal flap on facial morphology in patients with cleft lip and palate, we studied prospectively 20 consecutive patients with cleft lip and palate aged 4 to 9 years who needed a pharyngeal flap. We also studied a control group of 20 subjects matched with regard to age, sex, diagnosis, and method of primary treatment. Facial growth was followed for five years, beginning one year before operation. Before operation there was no significant difference between the operated group and the reference group as far as skeletal facial dimensions and angular measurements were concerned. The longitudinal comparison within each group showed that there was a change in mandibular growth direction backwards and downwards in the operated group. The changes in facial growth after pharyngeal flap operation were similar to those reported in patients with enlarged adenoids. Four years after operation, the change in the direction of mandibular growth did not result in any specific facial form that could be identified clinically.