Objective To study the effects of Gouteng Jiangya Jieyu Prescription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on learning and memory ability,hippocampal inflammatory response and autophagy-related protein expression in rats with hypertension complicated with depression(HD).Methods Thirty spontaneously hypertensive rats(SHR)were randomly divided into model group,positive control group(Levamlodipine Besylate 0.45 mg·kg-1+Fluoxetine Hydrochloride 1.80 mg·kg-1)and Gouteng Jiangya Jieyu Prescription high-,medium-and low-dose groups(25.38,12.69,6.34 g·kg-1).Another 6 SD rats were used as blank control group.The SHR rats were intervened by chronic mild unpredictable stress combined with solitary rearing to replicate the HD rat model.At the same time,intragastric administration was given once a day for 6 weeks.The systolic blood pressure and diastolic blood pressure of rat tail artery were measured by non-invasive sphygmomanometer.The learning and memory ability of rats was detected by Morris water maze test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope.The contents of interleukin-1β(IL-1β),IL-18 and IL-10 in hippocampus were detected by ELISA.The expression of autophagy-related proteins Beclin1 and Bcl-2 in hippocampus was detected by immunohistochemistry.The expression of autophagy-related proteins LC3Ⅰ and LC3Ⅱ in hippocampus was detected by Western Blot.Results Compared with the blank control group,the SBP and DBP of the rats in the model group were significantly increased from week 1-6(P＜0.01).The escape latency was significantly prolonged on the third and fourth day(P＜0.01).The first time of crossing the platform was significantly prolonged(P＜0.01),the times of crossing the platform area was significantly reduced(P＜0.05),and the retention time of the platform area was significantly shortened(P＜0.01).The neuronal cell body was obviously swollen,the ridge was destroyed,the nucleus was shrunk,and a large number of autophagosomes appeared;the contents of IL-1β and IL-18 in hippocampus were significantly increased(P＜0.01).The ratio of LC3Ⅱ/LC3Ⅰ protein expression and the expression of Beclin1 protein in hippocampus were significantly up-regulated(P＜0.05,P＜0.01),and the expression of Bcl-2 protein was significantly down-regulated(P＜0.01).Compared with the model group,the SBP of rats in the low-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at the weeks 1,3,4,5,6(P＜0.01),and the DBP was significantly decreased at weeks 1,3,4,5(P＜0.05,P＜0.01).The SBP of the rats in the medium-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at weeks 1,5,6(P＜0.01),and the DBP was significantly decreased at week 4(P＜0.05).The SBP of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased in the first week(P＜0.01).The escape latency of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the third day(P＜0.05),and the escape latency of rats in the high-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the fourth day(P＜0.05).The first crossing platform time of rats in the high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened(P＜0.01).The times of rats crossing the platform area in the medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription were significantly increased(P＜0.05),and the retention time in the platform area was significantly prolonged(P＜0.05).In the administration group,the degree of hippocampal neuron damage was reduced,the nuclear shrinkage was significantly improved,and the autophagosomes were reduced.The contents of pro-inflammatory factors IL-1β and IL-18 in the hippocampus of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription were significantly decreased(P＜0.05,P＜0.01).The content of anti-inflammatory factor IL-10 in the hippocampus of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly increased(P＜0.01).The protein expression ratio of LC3Ⅱ/LC3Ⅰ in hippocampus of high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.01),and the expression of Bcl-2 protein was significantly up-regulated(P＜0.01).The expression of Beclin1 protein in the hippocampus of the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Prescription can reduce the tail arterial pressure of HD rats,improve their learning and memory ability,and alleviate hippocampal neuronal damage.The mechanism may be related to reducing the release of inflammatory factors,increasing the level of anti-inflammatory factors,and regulating the expression of hippocampal autophagy-related proteins LC3Ⅱ/LC3Ⅰ,Beclin1 and Bcl-2.

AIM: To explore retinal microvascular changes in migraine patients using meta-analysis.METHODS: The National Library of Medicine PubMed, Embase, and Cochrane Library were searched to find relevant studies, and the search period was from the creation of database to June 2023. Two investigators independently screened the literatures, extracted data, and evaluated the quality of included studies using the NOS scale. STATA15.0 was used for Meta-analysis and publication bias evaluation, sensitivity analysis was performed for results with large heterogeneity, and the funnel plot and Egger were used to assess the publication bias of the literature.RESULTS:A total of 12 studies, including 217 patients(252 eyes)with migraine with aura(MA), 283 patients(388 eyes)with migraine without aura(MO), and 374 healthy individuals(479 eyes), were included in this Meta-analysis. Several optical coherence tomography angiography(OCTA)indicators, including foveal avascular zone(FAZ)macular or optic disc perfusion density were compared and analyzed. The Meta-analysis results showed that compared with healthy controls, patients with MA had a significant increase in FAZ area and perimeter, a significant decrease in perfusion density of the macular deep capillary plexus(mDCP)except for the fovea, and a significant decrease in perfusion density of the radial peripapillary capillaries(RPC)around the optic disc; the FAZ parameters were significantly increased in MO, while the differences in perfusion density of the macular superficial capillary plexus(mSCP), mDCP and RPC were not statistically significant, except for the perfusion density in the parafovea mDCP.CONCLUSIONS: Both MA and MO patients had an enlarged FAZ area, patients with MA had a significant decrease in mDCP perfusion density, and migraine patients had some degree of retinal ischemia.

Objective:To investigate the effect and mechanism of NOD-like receptor family pyrin domain containing 12 (NLRP12) knockdown on inflammatory factor levels and retinal injury in retinal ganglion cells (RGCs) of rats with high intraocular pressure.Methods:Seventy SPF adult male SD rats were selected and randomized into control group, high intraocular pressure (IOP) group, high IOP+ small interfering RNA negative control (siNC) group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ recombinant rat caspase-1 (rrcaspase-1) group, with 14 rats in each group.Rats in the control group were only treated with conjunctival incision in the right eye, and ocular hypertension model was established in the other four groups with external scleral vein cauterization.High IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group were injected with siNC, siNLRP12 and siNLRP12+ rrcaspase-1 reagent via the tail vein, respectively.The IOP of the right eye was measured at 1 day, 1, 2 and 3 weeks after the operation.Three weeks after the operation, the retinal structure was observed by hematoxylin-eosin staining, and the number of RGCs in each group was counted.RGCs were divided into control group, rrcaspase-1 group, siNC+ rrcaspase-1 group, siNLRP12+ rrcaspase-1 group.The cells in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group were treated with rrcaspase-1, siNC+ rrcaspase-1 and siNLRP12+ rrcaspase-1 reagent for 24 hours, respectively.No treatment was given to the control group.The expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins in RGCs and retinal tissue were detected by Western blot.The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat serum or cell culture supernatant were detected by enzyme-linked immunosorbent assay.The study protocol was approved by the Animal Ethics Committee of the First People's Hospital of Chenzhou (No.2020086).Results:Compared with control group, the IOP was higher in high IOP group at 1, 2 and 3 weeks after cauterization, and the differences were statistically significant (all at P<0.05). The retinal tissue was clear with the RGCs in a single layer arrangement in the control group.In the high IOP group and the high IOP+ siNC group, the RGCs layer was loose and the inner plexiform layer was thin.The inner plexiform layer was thickened in high IOP+ siNLRP12 group compared with high IOP group, and the RGCs layer was loose in the high IOP+ siNLRP12 group and the high IOP+ siNLRP12+ rrcaspase-1 group.The number of RGCs in control group, high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group was 119.31±23.25, 89.19±16.98, 88.87±13.92, 109.33±10.25 and 92.89±12.58, respectively, showing a statistically significant overall difference ( F=201.932, P<0.001). The number of RGCs was lower in the high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than the control group, higher in the high IOP+ siNLRP12 group than the high IOP+ siNC group, and lower in the high IOP+ siNLRP12+ rrcaspase-1 group than the high IOP+ siNLRP12 group, and the differences were statistically significant (all at P<0.05). The relative expressions of caspase-1 and cleaved-caspase-1 proteins and the concentrations of TNF-α and IL-1β in the retinal tissue were higher in high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than control group, higher in high IOP+ siNLRP12 group than high IOP+ siNC group, and higher in high IOP+ siNLRP12+ rrcaspase-1 group than high IOP+ siNLRP12 group (all at P<0.05). Relative expression levels of caspase-1 and cleaved-caspase-1 protein were increased in rrcaspase-1 group and siNC+ rrcaspase-1 group compared with control group, and relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 protein were decreased in siNLRP12+ rrcaspase-1 group compared with control group (all at P<0.05). The relative mass concentrations of TNF-α and IL-1β were increased in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group compared with the control group (all at P<0.05). Relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins and relative mass concentrations of TNF-α and IL-1β in siNLRP12+ rrcaspase-1 group were lower than those in siNC+ rrcaspase-1 group (all at P<0.05). Conclusions:Knockdown of NLRP12 can reduce the inflammatory response and retinal injury induced by high IOP by inhibiting the activation of caspase-1.

Objective:To evaluate the role of Dorea in glucose intolerance of people with obesity. Methods:This study recruited 113 young individuals with obesity and varying degree of glucose tolerance [body mass index(BMI)≥30 kg/m 2] and 105 controls, comparing the metabolic phenotypes and Dorea abundance. Correlation analysis and ROC analysis were performed to assess the association between Dorea and clinical parameters and its predictive role in predicting glucose intolerance. Results:(1) Metabolic parameters were higher in obesity group than the control group. There was no difference in body weight, BMI and WHR among subgroups classified by glucose tolerance in people with obesity. (2) The abundance of Dorea, Dorea formicigenerans were higher in obese individuals, however showing a downward trend in accordance with glucose intolerance. The abundance was inversely associated with OGTT-2 h plasma glucose and HbA 1C, while positively associated with HOMA-β. Logistic regression demonstrated that Dorea formicigenerans was an independent protective factor after adjusting confounders such as age and gender in the prevention of glucose intolerance. (3) ROC analysis exhibited that the AUC values of Dorea formicigenerans was 0.73 in the total population. Conclusion:Dorea and Dorea formicigenerans exert protective effect on glucose metabolism in obese subjects. The abundance of Dorea and Dorea formicigenerans can be used as predictors of glucose intolerance risk in obese subjects, which facilitate the early screening and monitoring.

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

AIM: To investigate the effects of transient receptor potential channel 6 (TRPC6) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) induced by IL-1β.METHODS: The mRNA expression of TRPC6 in synovial tissues from RA or OA patients was studied by RT-qPCR.RA-FLS were cultured by enzyme digestion and tissue adhesion methods.The method of flow cytometry was applied to identify the RA-FLS.RA-FLS were treated with different concentrations (0, 0.25, 0.5, 1, 2, 4, 8 and 16 μg/L) of IL-1β for 36 h.The cell viability was examined by CCK-8 assay.RA-FLS were incubated with IL-1β (16 μg/L) for different time (12, 24, 36, 48, 60 and 72 h), and the cell viability was measured by CCK-8 assay.The interference efficiency of TRPC6-siRNA was determined by RT-qPCR and Western blotting.After incubation in the presence or absence of IL-1β medium, the cell viability, the percentage of EdU-positive cells and the percentage of (G2/M+S) phase were measured by CCK-8 assay, EdU labeling assay and flow cytometry, respectively.RESULTS: The mRNA expression of TRPC6 was found in synovial tissue with higher levels in RA patients than that in OA patients.TRPC6-siRNA significantly decreased the mRNA and protein expression of TRPC6 (P<0.05).When RA-FLS were treated with IL-1β, the proliferation of RA-FLS was increased (P<0.05).The differences of the cell viability, the percentage of EdU-positive cells and the (G2/M+S) phase percentage between TRPC6-siRNA group and blank control group or NC-siRNA group were significant, in the presence of IL-1β (P<0.05).However, they were not significant in the absence of IL-1β.CONCLUSION: TRPC6 is involved in the proliferation of RA-FLS induced by IL-1β.Silencing of TRPC6 gene inhibits the growth of RA-FLS induced by IL-1β.

BACKGROUND:Triggering receptor expressed on myeloid cel s 2 (TREM-2) is highly expressed throughout the synovial tissue in active rheumatoid arthritis patients, but the role of TREM-2 in the pathogenesis of rheumatoid arthritis stil remains unclear.
OBJECTIVE:To explore the TREM-2 expression in the synovial tissue of col agen type II-induced arthritis rats.
METHODS:The col agen-induced arthritis models were established in rats. The activity indicators and pathological changes of arthritis synovial were dynamical y observed. The mRNA levels of TREM-2, tumor necrosis factor-α, interleukin-1β, and interleukin-10 were detected in synovial tissue of rats by RT-PCR. The protein expression and location of TREM-2 were measured with western blot assay and immunohistochemistry, respectively.
RESULTS AND CONCLUSION:At day 13 after immunization, the paws of model rats appeared red and swel ing, the arthritis index scores were increased (P<0.01). At day 19-25 after immunization, the inflammation reached the peak. Hematoxylin-eosin staining showed that, the synovium of col agen-induced arthritis rats were proliferated and were infiltrated by inflammatory cel s, cartilage was destroyed. Compared with the control group, the expression of TREM-2 mRNA and protein, the mRNA levels of tumor necrosis factor-αand interleukin-1βin synovial tissue of the model rats were significantly increased (P<0.05 or P<0.01), while interleukin-10 mRNA expression was significantly decreased (P<0.05). Experimental findings indicate that, TREM-2 is a crucial inflammatory regulator and the increasing expression of TREM-2 plays an important role in the pathogenesis of col agen-induced arthritis.

Objective To obtain a reliable estimate of the risk of H. pylori infection in causing pancreatic cancer ,by perform‐ing a M eta‐analysis of the existing observational studies evaluating the association .Methods Observational studies comparing the prevalence of H. pylori infection in patients with pancreatic cancer and healthy controls were identified through systematic search in the Medline ,EMBASE ,the Cochrane ,PubMed ,VIP database .H. pylori infection was confirmed by serological testing using an anti‐gen‐specific enzyme‐linked immunosorbent assay .Pooled adjusted odds ratios (AOR) and associated 95% confidence intervals (CI) were obtained by using a Dersimonian and Laird random‐effects model .Results Six studies involving a total of 2 335 patients met our eligibility criteria .A significant association between H. pylori seropositivity and development of pancreatic cancer (AOR=1 .38 , 95% CI:1 .08-1 .75 ;P=0 .009) was seen .No significant association had been seen on pooled analysis of the three studies assessing the relationship between CagA positivity and pancreatic cancer (AOR=1 .14 ,95% CI:0 .66-1 .97 ,P=0 .639) .Conclusion The da‐ta suggests an association between infection with H. pylori and the development of pancreatic cancer .Further research is needed to confirm our findings .

OBJECTIVE: To study the results of TEOAE and AABR hearing screening and follow-up in NICU. METHOD: Total 574 cases in NICU were included in this study, all cases received both TEOAE and AABR hearing screening while admission and rescreening when one-month-old. The cases that were abnormal on either test in rescreening were asked to return for diagnostic tests at 3 moths old. The patients who didn't return as required in 3 months were surveyed by call and analyzed. RESULT: Among 574 cases, 472 cases passed both TEOAE and AABR hearing screening while admission. While 102 cases had abnormal test results in either screening test. Thirty-three cases returned for follow-up, 13 of which passed rescreening test one month after discharge, the other 20 cases had ABR diagnostic tests after 3 months. Among them, 8 cases had normal hearing, 12 cases had various degree of hearing loss. Sixty-nine cases lost follow-up. The reason of lost follow-up was as follows, parents changed phone number/contact information, parents didn't understand the screening results, parents believe that their children having no need for further testing; parents had retest in other hospitals, parents didn't pay attention to hearing loss because of other severe complicated comorbidities. CONCLUSION The passing rate (normal) of TEOAE and AABR hearing screening in NICU was 82.2%, non- passing rate wass 17.8%, and the prevalence of hearing loss was high in those followed cases. Hyperbilirubinemia was the main risk factors of hearing loss in our NICU patients. We reviewed the reason for high rate (67.6%) of losing follow-up.
Female ; Follow-Up Studies ; Hearing Tests ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; statistics & numerical data ; Lost to Follow-Up ; Male ; Neonatal Screening ; Retrospective Studies

Objective To investigate the clinical and genetic characteristics in a male patient with 21hydroxylase deficiency combined with adrenal and testicular tumors.Methods Clinical features and laboratory data were collected from the patient.Testicular biopsy was performed.The CYP21 gene was sequenced for mutations.Results The patient presented left adrenal and testicular enlargements.The laboratory examinations showed that plasma ACTH,androstenedione,testosterone,progesterone,and 17-hydroxyprogesterone were markedly elevated.CT scan revealed that the right adrenal gland being resected and the left adrenal with nodular enlargement.Furthermore,testicular biopsy showed a prominent peritubular fibrosis with increased number of peritubular fibroblasts,tubular hyalinisation,and calcification.Sequencing analysis showed a A>G homozygous mutation at intron 2.Conclusion Patients with untreated 21-hydroxylage deficiency may.have adrenal adenomas and(or)testicular adrenal rest tumor simultaneously.