Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To evaluate the efficacy of ultrasound-guided median interspinous in-plane approach to subarachnoid puncture in obese pregnant patients.Methods:This study was a randomized controlled trial. Eighty obese parturients who underwent elective cesarean section from March 2022 to January 2024 in our hospital were divided into 2 groups( n=40 each) by the random number table method: median interspinous in-plane approach group(group M) and paramedian interlaminar in-plane approach group(group P). After successful puncture, 0.5% ropivacaine 15 mg(3 ml) was intrathecally injected in both groups. The first-attempt success of puncture, the number of puncture attempts, operation time, the total success of puncture, and the visibility scores of the anterior and posterior union, positioning structure(lamina in group P, spinous process in group M) and puncture needle under ultrasound were recorded. Results:Compared with group P, the visibility score of positioning structure under ultrasound was significantly increased, the success rate of puncture at the first attempt was increased, the number of puncture attempts was decreased, the operation time was shortened, the total success rate of puncture was increased( P<0.05), and no significant change was found in the visibility scores of the anterior and posterior union and puncture needle in group M( P>0.05). Conclusions:For obese pregnant patients, the ultrasound-guided median interspinous in-plane approach can accurately and quickly perform subarachnoid puncture, which has more advantages than the traditional paramedian interlaminar in-plane approach.

Objective:To evaluate the efficacy of ultrasound-guided median interspinous in-plane approach to subarachnoid puncture in obese pregnant patients.Methods:This study was a randomized controlled trial. Eighty obese parturients who underwent elective cesarean section from March 2022 to January 2024 in our hospital were divided into 2 groups( n=40 each) by the random number table method: median interspinous in-plane approach group(group M) and paramedian interlaminar in-plane approach group(group P). After successful puncture, 0.5% ropivacaine 15 mg(3 ml) was intrathecally injected in both groups. The first-attempt success of puncture, the number of puncture attempts, operation time, the total success of puncture, and the visibility scores of the anterior and posterior union, positioning structure(lamina in group P, spinous process in group M) and puncture needle under ultrasound were recorded. Results:Compared with group P, the visibility score of positioning structure under ultrasound was significantly increased, the success rate of puncture at the first attempt was increased, the number of puncture attempts was decreased, the operation time was shortened, the total success rate of puncture was increased( P<0.05), and no significant change was found in the visibility scores of the anterior and posterior union and puncture needle in group M( P>0.05). Conclusions:For obese pregnant patients, the ultrasound-guided median interspinous in-plane approach can accurately and quickly perform subarachnoid puncture, which has more advantages than the traditional paramedian interlaminar in-plane approach.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.