Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.

[Verification of clinical applicability of the non-special perioperative administration for enhanced recovery after surgery of gastric cancer patients: a Chinese single-center observational report].

Objective: To verify clinical applicability of the non-special perioperative administration for enhanced recovery after surgery (ERAS) proposed by Japanese scholars in Chinese gastric cancer patients. Methods: The main measures of the non-special perioperative administration for ERAS are as follows: (1) discussion of multiple disciplinary team before surgery; (2) rehabilitation education for patients; (3) no routine bowel preparation before surgery; (4) placement of nasogastric tube for decompression routinely before operation and removal as early as 24 hours after surgery; (5) appropriate rehydration; (6) antibiotic prophylaxis before surgery; (7) place abdominal drainage tubes when necessary; (8) epidural patient-controlled analgesia and oral medication for postoperative pain management; (9) start low-molecular-weight heparin injection 48h after surgery and ambulation every day to prevent deep vein thrombosis; (10) postoperative dietary management and supplement with parenteral nutrition intermittently; (11) remove Foley catheter about 24 hours after surgery. A retrospective cohort study was performed, including 203 patients undergoing radical gastrectomy at Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital from January 2017 to December 2018. Inclusion criteria were patients who were ≤75 years old without distant metastasis by preoperative examination, were diagnosed as gastric adenocarcinoma by postoperative histopathology and had complete clinicopathological and follow-up data. Patients with history of other malignancies and gastrectomy, extensive implantation of the abdominal cavity or malignant ascites by intraoperative exploration, death within 1 month after surgery, and residual gastric cancer were excluded. The perioperative management methods were chosen by patients. There were 123 patients who followed non-special perioperative administration for ERAS (non-special preparation group) and 80 patients who underwent traditional perioperative management (traditional method group). The primary outcomes (postoperative hospital stay, time to the first flatus, time to the first fluid diet, time to the first ambulatory activity, morbidity of postoperative complication, mortality, and readmission rate) and secondary outcomes (operative time, intraoperative blood loss and postoperative pain score) were compared between the two groups. Results: Compared to the traditional method group, the non-special preparation group had shorter time to the first flatus [(3.6±1.1) days vs. (4.8±1.4) days, t=3.134, P=0.003], shorter time to the first liquid diet [(2.6±0.9) days vs. (5.5±1.6) days, t=15.105, P<0.001], shorter time to the first ambulatory activity [(1.9±0.5) days vs. (4.1±1.1) days, t=8.543, P<0.001] and shorter postoperative hospital stay [(9.6±2.3) days vs. (12.9±2.3) days, t=5.020, P<0.001]. Besides, incidences of pancreatic leakage [6.5% (8/123) vs. 16.3% (13/80), χ(2)=4.964, P=0.026], lymphatic leakage [1.6% (2/123) vs. 13.8% (11/80), χ(2)=11.887, P=0.001], peritoneal effusion [2.4% (3/123) vs. 10.0% (8/80), χ(2)=4.032, P=0.045], and gastroparesis [0.8% (1/123) vs. 7.5% (6/80), χ(2)=4.657, P=0.031] in the non-special preparation group were significantly lower. The overall morbidity of postoperative complications and incidences of pulmonary infection and intestinal adhesion were not significantly different between the two groups (all P>0.05). As for the secondary outcomes, compared to the traditional method group, the non-special preparation group had less intraoperative blood loss [(80.4±24.4) ml vs. (100.5±19.4) ml, t=3.134, P=0.003] and lower postoperative pain score [postoperative day 1: (4.4±0.3) vs. (5.3±0.8), t=2.504, P=0.037],while the difference in operative time was not significant (P>0.05). Conclusion: The non-special perioperative administration for ERAS proposed by Japanese scholars is effective and safe, which has certain clinical applicability and value for Chinese patients with gastric cancer.

[Analysis of influencing factors on hepatic encephalopathy in patients with non-cirrhotic portal hypertension].

Objective: To investigate the incidence of hepatic encephalopathy (HE) in patients with non-cirrhotic portal hypertension (NCPH) and to explore its risk factors. Methods: The incidence rate of HE in 150 cases with NCPH was evaluated in two hospitals, and 188 cases of compensated cirrhosis patients were taken as control. Logistic regression was used to screen for independent risk factors for HE in patients with NCPH. Results: The incidence of overt hepatic encephalopathy (OHE) in patients with NCPH was not statistically significantly different from that in patients with cirrhosis (4.7% vs. 6.9%, P = 0.682). The incidence of mild hepatic encephalopathy (MHE) was significantly lower than that of cirrhosis patients (32.7% vs. 46.3%, P < 0.05). The presence of upper gastrointestinal bleeding, infection and portosystemic venous shunt were the main independent factors for HE in NCPH patients (OR > 1, P < 0.05). Conclusion: HE is one of the important complications of NCP, and may be influenced by factors such as upper gastrointestinal bleeding, infection and portosystemic venous shunt.

[Study of epidemiological characteristics and viral sources of dengue fever outbreak in Guangxi Zhuang Autonomous Region, 2014].

Objective: To understand the epidemiological characteristics and viral sources of dengue fever outbreak in Guangxi Zhuang Autonomous Region (Guangxi) in 2014. Methods: A combined analysis of epidemiological characteristics and genetic characteristics were performed in this study. The time, population and area distributions of the cases were analyzed. Serum samples were collected from dengue fever cases to detect NS1 antigen by using commercial ELISA kits according to the guideline of the manufacture. RT-PCR assay was conducted to detect dengue virus in NS1 positive samples. Phylogenetic tree based on E gene sequence of dengue virus were further analyzed. Results: During September-December 2014, an outbreak of dengue fever caused by dengue virus type 1 and 2 occurred in Guangxi, a total of 854 cases were reported without death, including 712 laboratory confirmed cases and 142 clinical diagnosed cases, in which 79.63% (680/854) occurred during 22 September-21 October 2014. All the cases had typical dengue fever symptoms. Most cases occurred in Nanning and Wuzhou, in which 83.61% (714/854) were in age group 15-59 years; 46.60% (398/854) were staff or people engaged in commercial service. A total 526 serum samples were tested for dengue virus serotype by RT-PCR assay. Among 414 positive samples, 345 were positive for dengue virus type 1 (DENV-1) and 69 were positive for dengue virus type 2 (DENV-2), no DENV-3 and DENV-4 were detected. The results of phylogenetic analysis of E gene sequence indicated that the sequences of 99.12%(113/114) of DENV-1 strains in Nanning in China shared 100.00% homology with the isolate (SG EHI D1/529Y13) from Singapore in 2013, which belonged to the genotype Ⅰ; All the DENV-2 isolates from Wuzhou shared 99.80% homology with the isolate (D14005) from Guangdong province, which belonged to genotype Cosmopolitan. Conclusions: The outbreak was caused by DENV-1 from Singapore and DENV-2 from Guangdong province in China. It is necessary to strengthen the surveillance and early warning for imported dengue fever, conduct vector control and improve the diagnosis of suspected dengue fever cases for the effective control of dengue fever outbreak.

Construction and characterization of recombinant adenovirus carrying a mouse TIGIT-GFP gene.

Recombinant adenovirus vector systems have been used extensively in protein research and gene therapy. However, the construction and characterization of recombinant adenovirus is a tedious and time-consuming process. TIGIT is a recently discovered immunosuppressive molecule that plays an important role in maintaining immunological balance. The construction of recombinant adenovirus mediating TIGIT expression must be simplified to facilitate its use in the study of TIGIT. In this study, the TIGIT gene was combined with green fluorescent protein (GFP); the TIGIT-GFP gene was inserted into a gateway plasmid to construct a TIGIT-GFP adenovirus. HEK 293A cells were infected with the adenovirus, which was then purified and subjected to virus titering. TIGIT-GFP adenovirus was characterized by flow cytometry and immunofluorescence, and its expression in mouse liver was detected by infection through caudal vein injection. The results showed the successful construction of the TIGIT-GFP adenovirus (5 x 10(10) PFU/mL). Co-expression of TIGIT and GFP was identified in 293A and liver cells; synthesis and positioning of TIGIT-GFP was viewed under a fluorescence microscope. TIGIT-GFP was highly expressed on liver cells 1 day (25.53%) after infection and faded 3 days (11.36%) after injection. In conclusion, the fusion of TIGIT with GFP allows easy, rapid, and uncomplicated detection of TIGIT translation. The construction of a TIGIT-GFP adenovirus, mediating TIGIT expression in vitro and in vivo, lays the foundation for further research into TIGIT function and gene therapy. Moreover, the TIGIT-GFP adenovirus is a helpful tool for studying other proteins (which could replace the TIGIT gene).

[Surveillance of filariasis in some vulnerable areas in Guangxi after filariasis elimination].

OBJECTIVE: To explore the measures for continuing surveillance of filariasis. METHODS: Selecting some vulnerable spots for focal surveillance, double-slide biood sampling for microfilaria examination, dissecting vectors for detecting the mosquitoes infected with filarial larva, using IFAT for detecting antifilarial antibody. RESULTS: 27,938 persons were examined for microfilaria and 4,454 mosquitoes were dissected for filaria larva, all were negative. 3,606 serum samples were examined for antifilarial antibody average positive rate was 1.35%(0.39-4.97%). CONCLUSION: The results of surveillance showed that the achievement of filariasis control in Guangxi after filariasis elimination is consolidated.

[The role of theophylline in the improvement of scop-induced learning and memory impairment].

Adenosine and ACh contents in hippocampus, striatum region around the nucleus of basal meynert (NBM) and the frontal and temporal parts of rat cortex were measured by a high performance liquid chromotography-electronic detector (HPLC-ECD). Adenosine content in 18~20 month-old rats was significantly higher than that of 3~6 month-old rats, while ACh content in 18~20 month-old rats was lower than that of 3~6 month-old ones. Learning and memory impairment models were established by induction of SD rats with scopolamine (0.5 mg/kg, ip), which were injected with an adenosine receptor antagonist theophylline (1.0 mg/5 microliter, icv), and the step-down test was performed. The error frequency in the step-down test decreased significantly (P<<0.05), and the retention time was longer than that of control. Furthermore, ACh content increased in all the three different brain regions. The above results suggest that adenosine may play an important role in senile learning and memory impairment, and theophylline may improve scopolamine-induced learning and memory impairment by increasing ACh content. In consequence, theophylline could be a promising drug for ameliorating senile learning and memory impairment.

Pre- and post-operative hypothalamic-pituitary-thyroidal axis function in patients with prolactinoma, growth hormone tumour and ACTH tumour.

Pre- and postoperative hypothalamic-pituitary-thyroid axis function was studied in 38 patients with pituitary adenomas (PRL, GH and ACTH tumours), of whom 35 were surgically confirmed and three diagnosed by clinical signs, CT scanning and hormone assessments. About ten days after operation, the same study was repeated in 10 patients with prolactinoma and 7 with growth hormone (GH) tumour. The preoperative abnormal serum TSH response to TRH was found in 8/20 patients with prolactinoma, 9/16 with GH tumour, and 2/2 with Cushing's disease due to ACTH microadenoma. The incidence of abnormal TSH response to TRH was not significantly increased in patients with larger adenoma in either PRL or GH tumour group. In 8 cases of prolactinoma, metoclopramide (MCP, 10 mg, P.O.) test was also performed and there was a significant positive correlation between TSH responses to TRH and to MCP. Serum TT3 in the GH tumour group was within normal ranges, but significantly higher than that of the normal and prolactinoma groups. After operation, TT3 was significantly decreased as compared with that before operation and there were marked changes in TSH response to TRH. In conclusion, there were some abnormalities in TSH control in patients with non-TSH pituitary tumour, and in serum TT3 control in patients with GH tumour. The surgical treatment of pituitary adenoma can lead to transient decrease in TSH reserve and serum TT3 level probably resulting from both stress and/or destruction of thyro-trophs by the operation.

Clinical significance of compound quinestrol-caused glucose intolerance.

PIP: A series of 146 women taking compound quinestrol (CQ) was tested for glucose tolerance and insulin release to determine the effects of CQ on these parameters. 23 normal subjects (6 male and 17 female) and 12 diabetics (7 male and 5 female) were also tested and their results were compared with those from the CQ-taking women. The curves of glucose tolerance, insulin release, release index during different phases, and the immunoreactive insulin-blood glucose (IRI-BG) distribution were compared. In this series, the insulin release curve, 45-minutes-after-release index, and IRI-BG distribution of subjects on CQ approximated those of normals, but differ dramatically from diabetic subjects. The glucose intolerance which accompanied the more active insulin reaction caused by CQ seems to gradually ameliorate or revert to normal after CQ withdrawal, a phenomenon which does not occur in true diabetics. Hence, the glucose intolerance caused by CQ is due to the drug's effect on the metabolism of carbohydrates or of insulin.^ieng