Aim To investigate the effect of vanillin on the regulation of cyclic guanylate adenylate synthetase(cGAS)/stimulator of interferon gene(STING)signa-ling pathway on hepatic tissue injury in rats with intra-hepatic cholestasis(IC).Methods SD rats were randomly divided into normal group,IC group,vanillin group,cGAS overexpression group,and vanillin+cGAS overexpression group,with continuous adminis-tration for seven days.The body weight,liver weight and liver to body weight ratio of rats were measured.Liver function(ALT,AST,ALP,LDH),IC(TBIL,TBA)and liver fibrosis(HA,LN,PC Ⅲ)index were determined by ELISA.Liver pathology and fibrosis were observed using HE and Masson staining,and col-lagen volume fraction was calculated.The expression of cGAS/STING pathway related proteins in liver tissue was detected by Western blot.Results Vanillin could improve liver pathology and fibrosis,increase body weight,and decrease liver weight,ALT,AST,ALP,LDH,TBIL,TBA,HA,LN,PC Ⅲ,collagen volume fraction,cGAS,STING protein in IC rats(P＜0.05).Overexpression of cGAS could reverse the effects of vanillin on the above indicators in IC rats(P＜0.05).Conclusions Vanillin may improve liver function,IC,liver fibrosis,and liver tissue damage in IC rats by downregulating the cGAS/STING signaling pathway.

ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.

AIM: To evaluate the changes of retinal microvascular density in patients with sellar region tumor, and its correlation with the damage to visual field, and to explore its application value in evaluating optic nerve injury of those patients.METHODS: Cross-sectional study. A total of 157 patients(292 eyes)with sellar region tumor, including 82 cases(152 eyes)of pituitary adenoma and 75 cases(140 eyes)of craniopharyngioma, were selected from neurosurgery department and ophthalmology department of Beijing Tiantan Hospital, Capital Medical University between October 2018 and May 2022. A total of 90 people(180 eyes)during the same period, including the family members of patients, students and staff in Beijing Tiantan Hospital, Capital Medical University were collected as control group. All participants underwent optical coherence tomography angiography(OCTA)examination. The changes of retinal microvascular density and its correlation with visual field parameters were compared between the two groups.RESULTS: In patients with sellar region tumor, the radial peripapillary capillary(RPC)and superficial retinal capillary plexus(SRCP)density were significantly lower than that in the control group [50.81%(46.49%, 53.49%)vs. 52.78%(50.73%, 54.51%)and 50.57%(48.13%, 52.73%)vs. 51.63%(49.78%, 53.02%), all P<0.05]. The RPC density in the craniopharyngioma group was lower than that in the pituitary adenoma group [49.71%(44.33%, 53.14%)vs. 51.37%(47.42%, 53.95%), P<0.05]. The MD, PSD and VFI of the sellar region tumor group were -4.33(-12.22, -1.85)dB, 3.37(1.91, 8.82)dB and 92%(65%, 97%)respectively. RPC density of patients with sellar region tumor was positively correlated with MD and VFI, and was negatively correlated with PSD. The SRCP density of each quadrant was positively correlated with MD, and was positively correlated with VFI except Para-T and it was negatively correlated with PSD(all P<0.05).CONCLUSION: Retinal microvascular changes were present in patients with sellar region tumor. Lower vessel density indicates more severe damage to visual field. In the clinic, visual field examinations combined with OCTA were helpful to find the optic nerve injury of patients.

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.
COVID-19 ; Consensus ; Humans ; Oral Health ; Oral Medicine

OBJECTIVE: To observe the pressure pain threshold (PPT), skin conductance (SC) and blood perfusion (BP) of the sensitized acupoints in patients with knee osteoarthritis (KOA), and explore the mechanism of acupuncture at the sensitized acupoints for treating diseases. METHODS: Eleven healthy subjects and 11 unilateral KOA patients were recruited from July 2020 to March 2021 in this study. The PPT, SC and BP of control acupoints in healthy controls, and non-sensitized and sensitized acupoints in KOA patients were measured and compared between baseline and after manual acupuncture (MA) treatment. RESULTS: Before MA treatment, lower PPT was observed at the sensitized acupoints compared with non-sensitized and control acupoints (P<0.05). After MA treatment, PPT at the sensitized acupoints increased significantly in KOA patients (P<0.05). Before MA treatment, there was no statistical difference in SC and BP among control, non-sensitized and sensitized acupoints (P>0.05). Compared with the control and non-sensitized acupoints, there were significant increases of SC and BP in sensitized acupoints of KOA patients after MA treatment (P<0.05 or P<0.01). CONCLUSION MA at sensitized acupoints could elevate PPT of KOA patients, which may be associated with the increment of SC and BP.
Humans ; Acupuncture Points ; Pain Threshold ; Osteoarthritis, Knee/therapy* ; Acupuncture ; Acupuncture Therapy ; Pain

OBJECTIVE: To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH). METHODS: A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group. RESULTS: Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study. CONCLUSION Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.
Anticoagulants/therapeutic use* ; Hemorrhage ; Heparin, Low-Molecular-Weight/therapeutic use* ; Humans ; Panax notoginseng ; Prospective Studies ; Saponins/therapeutic use* ; Venous Thrombosis/prevention & control*

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective:This paper constructs a generalized regression neural network （GRNN） model to predict the disintegration time of traditional Chinese medicine （TCM） tablets. Method:Taking Astragali Radix as a model drug， the mixed Astragali Radix powders with different powder properties were prepared by mixing Astragali Radix extract powders with microcrystalline cellulose and lactose， which were made to Astragali Radix tablets by direct compression method. The powder properties of mixed Astragali Radix powders and the disintegration time of Astragali Radix tablets were determined， respectively. The correlation between the original data was eliminated by principal component analysis （PCA）. The principal component factors were used as the input layer of the GRNN model， and the disintegration time was used as the output layer for network training. Finally， the verification group data was used to predict the disintegration time， and the network prediction accuracy was calculated by comparing with the actual value. Result:Three principal component factors were obtained through PCA by analyzing the original nine variables that were correlated with each other （Hausner ratio， true density， tap density， compression degree， angle of repose， bulk density， porosity， water content and total dissolved solids）， which reduced the complexity of the network. The prediction value of the disintegration time based on this prediction method was in good agreement with the actual value， the error of disintegration time was 0.01-1.34 min and the average relative error was 3.16%. Conclusion:Based on the GRNN mathematical model， the physical properties of Astragali Radix extract powders can be used to accurately predict the disintegration time of Astragali Radix tablets， which provides a reference for studying the disintegration time of TCM tablets.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Virtual autopsy is a new technique for investigating the morphological changes of cadaveric tissues and organs by medical imaging technology. It has been widely used in the identification of causes of death. Multislice spiral computed tomography （MSCT） has become a routine inspection method in some identification institutions, although it cannot completely replace traditional autopsy, it plays a key auxiliary or substitute role in the identification of certain abnormal causes of death. Plain MSCT scan cannot visualize cadaveric vessels, but can perform cadaveric angiography to determine vascular injury or disease. This technology has entered a rapid development period in recent years, and has made a considerable progress in contrast agent, perfusion methods and imaging methods. This article summarizes several common cadaveric MSCT angiography methods, such as systemic angiography, angiography through cardiopulmonary resuscitation, targeted angiography, and angiography by cardiac puncture, and analyzes and compares the application prospects.
Angiography ; Autopsy ; Coronary Angiography ; Heart ; Humans ; Tomography, Spiral Computed