[The role of NLRP3 inflammasome pathway in silicosis-induced pulmonary fibrosis and its prospect as a therapeutic target].

Inhalation of crystalline silicon dioxide particles can induce silicosis, and the development of silicosis is closely related to the occurrence and development of pulmonary inflammation and pulmonary fibrosis. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been established as a major proinflammatory receptor for sensing environmental danger signals. Activation of NLRP3 inflammasomes after phagocytosis of silicon dioxide particles by pulmonary macrophages may be an important mechanism to induce oxidative stress and sustained inflammatory response in the lung. This article summarizes the role of NLRP3 inflammasome in the inflammatory response and pulmonary fibrosis in silicosis, and analyzes it as a potential target for silicosis treatment.

[Mechanism of Leakage in Phosphatidylserine-Containing Membranes by Melittin].

Phosphatidylserine (PS) is an important apoptotic-cell surface signal that exists in bacterial and cancer cells. The mechanism by which melittin interacts with the PS membrane remains unclear. Here, we revealed this mechanism by using a dual-channel fluorescence microscope to observe the concentration-dependent process of pore formation in giant unilamellar vesicles (GUVs) that were exposed to melittin solution. We found that unsaturated PS membranes differed significantly from saturated PS membranes in different phases. This study provides a reference for research and development of anticancer drugs.

[Clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis].

Objective: To investigate the clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Methods: A retrospective observational study was conducted. From May 2018 to February 2020, 8 patients with pressure ulcers on the ischial tuberosity combined with chronic osteomyelitis who met the inclusion criteria were admitted to Fuyang Minsheng Hospital, including 5 males and 3 females, aged 38-69 years, with unilateral lesions in 6 patients and bilateral lesions in 2 patients. According to the anatomical classification of Cierny-Mader osteomyelitis, there were 6 patients (7 sides) with focal type, and 2 patients (3 sides) with diffuse type. The wound areas were 3 cm×2 cm to 12 cm×9 cm on admission. The pressure ulcer and chronic osteomyelitis lesions were completely removed by en bloc resection and debridement. The chronic infectious lesions were transformed into sterile incisions like fresh wounds by one surgical procedure, and the gluteus maximus muscle flaps with areas of 10 cm×6 cm to 15 cm×9 cm were excised to transfer and fill the ineffective cavity. The wounds of 5 patients were sutured directly, and the wounds of 3 patients were closed by local flap transfer. The intraoperative blood loss volume and blood transfusion, and length of hospital stay of patients were recorded. The incision healing and flap survival of patients were observed after operation. The recurrence of pressure ulcer and osteomyelitis, the appearance of the affected area, and the secondary dysfunction and deformity of the muscle flap donor site of patients were observed during followed up. Results: The intraoperative blood loss volume of the 8 patients was 220 to 900 (430±150) mL; 5 patients received intraoperative blood transfusion, of which 2 patients received 3 U suspended red blood cells and 3 patients received 2 U suspended red blood cells. The length of hospital stay was 18 to 29 (23.5±2.0) d for the 8 patients. In this group of patients, the incisions of 7 patients healed, while in one case, the incision suture was torn off during turning over and healed after secondary suture. The flaps survived well in 3 patients who underwent local flap transfer. During the follow-up period of 6-20 months, no recurrence of pressure ulcer or osteomyelitis occurred in 8 patients, the affected part had skin with good texture, mild pigmentation, and no sinus tract formation, and no secondary dysfunction or deformity occurred in the donor site. Conclusions: The en bloc resection and debridement combined with gluteus maximus muscle flap has good clinical effects on ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Neither pressure ulcer nor osteomyelitis recurs post operation. The skin texture and appearance of the affected area are good, and the donor site has no secondary dysfunction or deformity.

IL-10 gene polymorphism in diabetic retinopathy.

INTRODUCTION: To investigate the relationship between the interleukin-10 (IL-10) gene polymorphism and the pathogenesis of diabetic retinopathy (DR). PATIENTS AND METHODS: According to the fundus examination report, 420 patients with diabetes were divided into the non-DR group (n=200) and the DR group (n=220). The single nucleotide polymorphisms rs1145612 and rs11567245 in the promoter region of the IL-10 gene were classified by the conformational differential gel electrophoresis. RESULTS: No correlation was found between the polymorphism rs1145612 and the clinical information of DR patients. The polymorphism rs11567245 had correlations with multiple clinical indicators of DR patients, including body mass index (BMI), systolic blood pressure (SBP), blood urea nitrogen (BUN), fasting blood glucose (FBG), and 2-h postprandial blood glucose (2hBG) (p<0.05). CONCLUSIONS: The IL-10 gene promoter rs1145612 is not related to the occurrence and development of DR, but a relationship exists between the polymorphism rs11567245 and the occurrence and development of DR.

[The effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction: a cohort study].

Objective: To investigate the effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Methods: From May 2013 to September 2014, a total of 3 474 pregnant women who took their first antenatal care and willing to undergo their prenatal care and delivery in Ma 'anshan Maternity and Child Care Centers were recruited in the cohort study. Excluding subjects without weight data before delivery (n=54), pregnancy termination (n=162), twins live births (n=39), without fetal birth weight data (n=7), 3 212 maternal-singleton pairs were enrolled for the final data analysis. Demographic information of pregnant woman, pregnancy history, disease history, height and weight were collected. In the 24(th)-28(th), 32(nd)-36(th) gestational week and childbirth, three follow-up visits were undertaken to collect data of pregnancy weight, pregnancy vomiting, gestational hypertension, gestational diabetes mellitus, newborn gender and birth weight. χ(2) test was used to compare the detection rate of fetal growth restriction in different groups. Multivariate unconditional logistic regression model and spreadsheet were used to analyze the independent and interaction effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Results: The incidence of fetal growth restriction was 9.7%(311/3 212). The incidence of fetal growth restriction in pre-pregnancy underweight group was 14.9% (90/603), higher than that in normal pre-pregnancy weight group (8.7% (194/2 226)) (χ(2)=24.37, P<0.001). The incidence of fetal growth restriction in inadequate increase of gestational weight group was 17.9% (50/279), higher than the appropriate increase of weight group (11.8% (110/932)) (χ(2)=36.89, P<0.001). Multivariate unconditional logistic regression analysis showed that compared with normal pre-pregnancy weight group, pre-pregnancy underweightwas a risk factor for fetal growth restriction, with RR (95%CI) at 1.76 (1.34-2.32); Compared with the appropriate increase of gestational weight group, inadequate weight increase during pregnancy was a risk factor for fetal growth restriction, with the RR (95%CI) at 1.70 (1.17-2.48). No additive model interaction [relative excess risk of interaction, attributable proportions of interaction, the synergy index and their 95%CI were 0.75 (-2.14-3.63), 0.21 (-0.43-0.86) and 1.43 (0.45-4.53), respectively] or multiplication model interaction (RR (95%CI): 1.00 (0.44-2.29)) existed between pre-pregnancy underweight and inadequate increase of gestational weight on fetal growth restriction. Conclusion: Pre-pregnancy underweight and inadequate increase of gestational weight would increase the risk of fetal growth restriction without interaction.

[Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients. METHODS: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use. Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI. Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels. Logistic models were applied in multiple analysis adjusting for possible confounders. RESULTS: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years. Among them, 78.3% were on hypoglycemic therapy. The cutoff points of quartiles of VAI were calculated for the males and females, respectively. According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e. Q1, Q2, Q3, and Q4. The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001). After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM. Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128 to 2.088), respectively (trend P=0.003). With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282). CONCLUSION: The glycemic control among the patients with T2DM is significantly associated with VAI. High level of VAI is an indicator of poor glycemic control.

Environmental fate of endocrine-disrupting dimethyl phthalate esters (DMPE) under sulfate-reducing condition.

Dimethyl phthalate esters (DMPE) can easily be released into the environment from plastic products. As endocrine disruptors, DMPE mimic estrogenic activities in animals and humans. The metabolites of DMPE are suspected to cause even more serious health problems. Among the common sterilization techniques adopted in the study of DMPE degradation, the average loss of the parent DMPE compounds after autoclaving was as high as 21.26%. In contrast, the loss after 0.2 microm filtration was significantly lower at 2.28%. It is suggested that filtration should be used over autoclaving for sterilizing DMPE. The environmental fate of DMPE under sulfate-reducing condition was simulated and studied in microcosm system. It was observed that dimethyl phthalate (DMP), dimethyl isophthalate (DMI) and dimethyl terephthalate (DMT) could not be mineralized over an extended period of 6 months, but with the transformation to the respective monomethyl phthalate and/or phthalic acid. The dominant species of microorganisms utilizing individual DMPE isomer as the sole carbon source were isolated and identified as facultative anaerobe Thauera sp., Xanthobacter sp. and Agrobacterium sp. for DMP, DMI and DMT, respectively. This study illustrates that the detrimental DMPE and their natural metabolites may accumulate in the sulfate-reducing environment. Accordingly, proper surveillance program should be devised to monitor both the parent compounds and degradation intermediates of DMPE in order to protect the aquatic ecosystem and human health.

Serotonin modulates retinotectal and corticotectal convergence in the superior colliculus.

A dense serotonin (5-HT)-containing projection to the superficial layers of the superior colliculus (SC) has been demonstrated in diverse mammalian species, but how 5-HT may affect visual signals within these laminae is largely unknown. This study undertook to investigate the distribution of 2 types of 5-HT receptors in the SC and to ascertain their physiological effects on transmission of visual signals to the SC from the retinotectal and corticotectual pathways. Autoradiography of tissue sections exposed to [3H]-8-OH-DPAT (8-hydroxy-dipropylaminotetraline) or to [125I]cyanopindolol plus isoproterenol showed that 5-HT1A and 5-HT1B receptors, respectively, were present in the superficial SC layers. In unilaterally enucleated animals, binding of ligand to 5-HT1B receptors was greatly reduced on the deafferented (contralateral) side, which is consistent with the possibility that these receptors are located on preterminal axons. Binding to 5-HT1A receptors was unaltered by enucleation. In recordings of superficial layer neurons from SC slices, application of 5-HT during blockade of 5-HT1A receptors with spiperone reduced the amplitude of EPSPs evoked by stimulation of the optic tract. The 5-HT concentration for a 50% reduction in EPSP amplitude was 6 microM. Under these conditions, there were no significant alterations in either membrane potential or input resistance concurrent with 5-HT mediated reduction in EPSPs. During extracellular in vivo recordings, 5-HT, applied by iontophoresis or micropressure or by endogenous release produced by electrical stimulation of the dorsal raphé nucleus, strongly suppressed visual activity in SC neurons. The effectiveness of 5-HT application was significantly stronger on responses evoked by electrical stimulation of the optic chiasm (an average response decrement of 92.2%) than on these evoked in the same neurons by stimulation of visual cortex (an average response reduction of 32.3%). These results support the following conclusions. The 5-HT1B receptors are located preferentially on optic axon terminals and exert presynaptic inhibition of retinotectal inputs. Secondly, 5-HT1A receptors probably have a postsynaptic localization and may affect activity of SC neurons irrespective of the source of input. The combined effect of 5-HT at both subtypes would bias SC visual activity toward information received from the corticotectal pathway.

[The exciting origin of guinea-pig inferior mesenteric ganglion neurons in vivo].

Intracellular recording in vivo showed that spontaneous activities of guinea-pig inferior mesenteric ganglion (IMG) neurons were inhibited when any one of the four groups of the nerves connected to the IMG was cutted or blocked, indicating that all the four groups of nerves sent in excitatory input. Colonic and hypogastric nerves convey the peripheral excitation respectively from colon and bladder. Intermesenteric nerve sends in peripheral excitatory input from colon and central from spinal cord. This finding suggests that the excitation of the prevertebral ganglia originates from not only spinal cord as claimed tranditionally, but also the peripheral organs. The latter exits stronger effect than the former. It seems that IMG is an integration neurocenter rather than a simple signal relay station from the central nervous system to peripheral effectors.

Effects of 5-HT on thalamocortical synaptic transmission in the developing rat.

1. Recent immunocytochemical and receptor binding data have demonstrated a transient somatotopic patterning of serotonin (5-HT)-immunoreactive fibers in the primary somatosensory cortex of developing rats and a transient expression of 5-HT1B receptors on thalamocortical axons from the ventral posteromedial thalamic nucleus (VPM). 2. These results suggest that 5-HT should strongly modulate thalamocortical synaptic transmission for a limited time during postnatal development. This hypothesis was tested in intracellular recording experiments carried out in thalamocortical slice preparations that included VPM, the thalamic radiations, and the primary somatosensory cortex. Effects of 5-HT and analogues were monitored on membrane potentials and input resistances of cortical neurons and on the amplitude of the synaptic potentials evoked in them by stimulation of VPM. 3. Results obtained from cortical neurons in slices taken from rats during the first 2 wk of life indicated that 5-HT strongly inhibited the VPM-evoked excitatory postsynaptic potential (EPSP) recorded from cortical neurons in a dose-dependent manner. In contrast, 5-HT had no significant effects on membrane potential, input resistance, or depolarizations induced by direct application of glutamic acid to cortical cells. 4. The effects of 5-HT were mimicked by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline maleate and antagonized by the 5-HT1B receptor antagonist (-)-pindolol. The 5-HT1A agonist [(+/-)8-hydroxydipropylaminotetralin HBr] (8-OH-DPAT) had less effect on the VPM-elicited EPSP, and the effects of 5-HT upon this response were generally not antagonized by either 1-(2-methoxyphenyl)-4-[4-(2- phthalimmido)butyl]piperazine HBr (a 5-HT1A antagonist) or ketanserine (a 5-HT2 antagonist) or spiperone (a 5-HT1A and 2 antagonist). 5. The ability of 5-HT to inhibit the VPM-evoked EPSP in cortical neurons was significantly reduced in slices from animals > 2 wk of age. The effectiveness of TFMPP in such animals was even more attenuated than that of 5-HT, and the effectiveness of 8-OH-DPAT was unchanged with age. These results are consistent with the disappearance of 5-HT1B receptors from thalamocortical axons after the second postnatal week and the maintenance of 5-HT1A receptors on some neurons. 6. All of the results obtained in this study are consistent with the conclusion that 5-HT has a profound, but developmentally transient, presynaptic inhibitory effect upon thalamocortical transmission in the rat's somatosensory cortex.

[Effect of Chinese herbal preparation on major constituents of bile of gallstones patients].

From 1991 to 1993, 51 patients in 3 groups who had received biliary operation with T tube drainage were selected for observation of dynamic change in bile acid, bilirubin, cholesterol and mucin in the bile within 3 days after taking the Danyihewei granule (DYHW) and Rongshisan (RSS). Result showed that in DYHW group the bile acid increased significantly on the 2nd and 3rd day (P < 0.01), along with significant lowering of bilirubin (P < 0.01) and mucin (P < 0.05, P < 0.01) in 1st through 3rd day. In the RSS group the bile acid remarkably increased on the 3rd day (P < 0.05) with significant reduction of bilirubin (P < 0.01) on 2nd and 3rd day. The control group showed no remarkable change. The bile acid/bilirubin and bile acid/cholesterol ratios all had a dynamic increase with 3 days in treated group. Whereas the control group remained unchanged. Therefore the DYHW and RSS were able to produce a strong inhibitory effect on stone-forming bile through regulation of liver and discharge of bile.

Modulation of retinotectal transmission by presynaptic 5-HT1B receptors in the superior colliculus of the adult hamster.

1. Radioligand binding with [125I]-cyanopindolol in the presence of isoproterenol was used to define the distribution of 5-HT1B receptors in the superior colliculus (SC) of adult hamsters. There was a high density of these receptors in the stratum griseum superficiale (SGS), and they were much less dense in other SC laminae. Enucleation of one eye produced a marked reduction in the density of these receptors in the contralateral SGS, suggesting that they are located primarily on retinotectal axon terminals. 2. Intracellular recording techniques were used to evaluate the effects of serotonin (5-HT) on the excitatory postsynaptic potentials (EPSPs) evoked in SC cells of adult hamsters by stimulation of the optic tract (OT) in vitro. Application of 5-HT produced a reduction of > or = 50% in OT-evoked EPSPs in 79% of the 67 cells tested. The average EPSP amplitude was 7.8 +/- 2.1 (SD) mV under control conditions and 2.7 +/- 1.9 mV in the presence of 5-HT (P < 0.01). For most of these neurons, application of 5-HT had little effect on their membrane potential or input resistance. The average percent change in membrane potential for cells tested with 5-HT was 0.5 +/- 6.0% and the average percent change in input resistance was 0.6 +/- 22.9%. 3. For four of six cells tested, application of 5-HT had no significant effects on the responses evoked by application of glutamate, either under normal bathing conditions or when the medium included low Ca2+ and high Mg2+. 4. Pharmacologic experiments indicated that the effects of 5-HT on retinotectal transmission were mimicked by the 5-HT1B agonists 1-[3-(trifluoromethyl)phenyl]-piperazine and 7-trifluoromethyl-4(4-methyl-1-piperazinyl) [1,2-a]-quinoxaline maleate and antagonized by the 5-HT1A/1B antagonists (-)-pindolol and methiothepin. The effects of 5-HT on the OT-evoked EPSP were not antagonized by either spiperone, ketanserin, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine HBr, or [1-H-3 alpha-5 alpha-tropan-3-yl]-3,5-dichlorobenzoate. 5. Both the anatomic and physiological results are consistent with the conclusion that 5-HT presynaptically inhibits retinotectal transmission and that this effect is mediated by the 5-HT1B receptor.

Complications of laparoscopic cholecystectomy: an analysis of 200 cases.

Complications of the initial 200 cases of laparoscopic cholecystectomy (LC) at the Cathay General Hospital within a period of 11 months were reviewed from video documents of the operations and clinical records. The major complication rate was 3.5%, including one common bile duct (CBD) injury (0.5%), three retained CBD stones (1.5%), one subphrenic fluid accumulation (0.5%), one liver abscess (0.5%) and one cystic duct stump bile leakage (0.5%). All major complications were cholecystectomy-related, and only one of the seven occurred in cases of acute cholecystitis. Age and sex were not related to its occurrence. The rate of minor complications ranged from 0.5% to 10%; they were: shoulder and back pain (10%), gall bladder perforation (10%), retained stones in the abdominal cavity (5%), transient nausea and diarrhea (5%), extension of umbilical port to a mini-laparotomy (3.5%), prolonged operation time > three hours (2%), subcutaneous emphysema (1.5%), wound infection (1.5%) and prolonged ileus (0.5%). The minor complications occurred largely in patients with acute cholecystitis. The complications occurred mostly during the early period of our study, indicating a learning period phenomenon. These could have been avoided if we had had a thorough knowledge of the potential complications and had strictly followed the principles of laparoscopic surgery. We conclude that LC is safe and the complication rate is not higher than that for open cholecystectomy. Most of the complications are preventable if LC is performed by qualified biliary surgeons following strict precautions.

The effects of suppressive activities mediated by cells on the protection of fetus against maternal immune rejection.

Using both mixed lymphocyte reaction (MLR) and graft-versus-host reaction (GVHR) assays, investigations have been made on 60 multiparous mice of late pregnancy, derived from C57BL mating with SWI as well as C57BL mating with BGI. The results demonstrate the presence of suppressor cells both in uterus-draining-lymphnodes (DLN) and in spleen of allogeneic pregnant mice. The suppressive immune regulatory activity mediated by these cells might play an important role in the successful maintenance of fetus allograft. The possible mechanisms about the inducing of the changes in lymphocyte subpopulation are also studied in this paper.

A preliminary study on the mechanism of neonatal allotransplantation tolerance. Participation of suppressor cells in the mediation of neonatal allotransplantation tolerance.

Using a method from Billingham, an animal model of the neonatal allotransplantation tolerance of SWI to C57BL inbred mice was established and the mechanism of neonatal tolerance established by us was preliminarily studied. Our experiment indicates that the clonal deletion theory is not the unique explanation for the neonatal tolerance and a peripheral active inhibitory mechanism including suppressor cells may participate in mediating and maintaining the neonatal tolerance. The suppressor cells in the neonatal tolerance are radioresistant, but rather sensitive to mitomycin C treatment. These results suggest that suppressor cell population may be nonhomogenous. Further studies about this problem are needed.