Objective:To identify independent risk factors for chronic critical illness (CCI) secondary to severe pneumonia and to develop and validate a clinical prediction model.Methods:A retrospective cohort study was conducted using electronic medical records from 415 patients with severe pneumonia admitted between January 2023 and March 2024. Patients were randomly divided into a training set ( n = 290) and a validation set ( n = 125) at a 7:3 ratio. Univariate and multivariate logistic regression analyses were used to identify independent risk factors, and a nomogram was constructed. The model’s discriminative ability, calibration, and clinical utility were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results:The overall incidence of CCI was 23.13% (96/415). Multivariate analysis identified five independent predictors: virus infection ( OR = 13.00, 95% CI: 5.07–33.35, P < 0.001), mechanical ventilation ≥72 hours ( OR = 8.06, 95% CI: 3.68–20.09, P < 0.001), neutrophil-to-albumin ratio (NAR) ( OR = 27848, 95% CI: 193.93–5542274.11, P < 0.001), oxygenation index ( OR =1.09, 95% CI: 1.01–1.09, P < 0.001), and age ( OR = 0.94, 95% CI: 0.91–0.97, P < 0.001). The model demonstrated excellent performance in both sets: training set AUC = 0.96 (95% CI: 0.94–0.98), sensitivity 0.93, specificity 0.89, Brier score 0.09; validation set AUC = 0.93 (95% CI: 0.88–0.98), sensitivity 0.89, specificity 0.64, Brier score 0.13. Calibration curves showed high consistency between predicted and observed risks (mean absolute error < 3%), and DCA indicated significant net clinical benefit within the threshold probability range of 15–60%. Conclusions:The developed prediction model integrates etiological, inflammatory, metabolic, and respiratory support parameters and demonstrates outstanding predictive performance (AUC > 0.90). It may serve as a quantitative tool for early risk stratification and intervention in patients with severe pneumonia. Further multicenter external validation and exploration of integrating dynamic biomarker monitoring are recommended.

Objective:To observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

Objectives: Type 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM. Methods: This is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study. Patients who sustained falls with and without hip fractures were matched by propensity score (PS) at a 1:1 ratio. Competing risk regression was used to evaluate the association between hip fracture and incident T2DM, with death being the competing event. Results: A total of 23,314 hip fracture cases were matched to 23,314 controls. The median follow-up time was 5.09 years. The incidence rate of T2DM was 11.947 and 14.505 per 1000 person-years for the hip fracture and control group respectively. After accounting for the competing risk of death, the hip fracture group had a significantly lower risk of developing T2DM (HR: 0.771, 95% CI: 0.719–0.827). Similar results were observed in all subgroups after stratification by age and sex. Conclusions Hip fracture was found to be associated with a reduced risk of T2DM. These findings provide insight into the topic of bone and glucose metabolism and prompt further research in evaluating the role of bone health in the management of T2DM.

Objective: To propose reasonable suggestions to promote the standardization of clinical studies by reviewing the systematic reviews and meta-analyses of acupuncture-moxibustion treatment of essential hypertension (EH). Methods: Computer retrieval was conducted through Excerpta Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure (CNKI), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and Wanfang Academic Journal Full-text Database (Wanfang) to collect systematic reviews and meta-analyses relevant to treating EH with acupuncture-moxibustion therapy. The time range was from the database's inception till July, 2020. The studies were screened based on the inclusion and exclusion criteria and then data-extracted. The study's quality and evidence ratings were performed by referring to the preferred reporting items for systematic review and meta-analysis (PRISMA), a measurement tool to assess systematic reviews 2 (AMSTAR 2), and the grading of recommendations, assessment, development, and evaluation (GRADE). Results: A total of 14 studies, 10 in Chinese and 4 in English, published between 2012 and 2019, were included, involving 70 outcome measures. The methodological quality was rated as critically low, the reporting was relatively complete or had certain flaws, and the evidence strength was rated as low or very low. Conclusion: Regarding the acupuncture-moxibustion treatment of EH, the methodological quality and outcome measure evidence of existing systematic reviews and meta-analyses are relatively low, and the reporting quality also expects further improvements.

Objective:To observe the clinical effectiveness of manual therapy based on posture decoding for patients with lower crossed syndrome (LCS).Methods:Thirty-six LCS patients were randomly divided into an observation group and a control group, each of 18. The observation group received manual therapy based on posture decoding, while the control group was treated with proprioceptive neuromuscular facilitation (PNF), both in 20min sessions, once a week for 4 weeks. Before the experiment, after one, two and four weeks of treatment and followed-up 4 and 8 weeks later, both groups were evaluated using a visual analogue scale (VAS), the Oswestry Disability Index (ODI) and finger-floor distance (FFD). Anterior pelvic tilt angles (ASIS-PSISs), sacral slopes (SS), lumbar curve index (LCI) and surface EMG flexion-relaxation ratios (FRRs) were also recorded from both groups before and after the treatment.Results:After one and four weeks of the treatment, the average VAS, ODI, and FFD had decreased significantly in both groups, with all significantly lower in the observation group, on average. At the final follow-up, the average VAS and ODI scores of both groups were significantly lower than before the treatment, with those of the observation group significantly lower than the control group′s averages. After 4 weeks of treatment significant differences were observed also in the group′s average ASIS-PSISs, SSs and LCIs compared with before the treatment. And right after the treatment the left and right surface electromyography FRRs of the observation group were significantly higher than those of the control group.Conclusion:Manual therapy based on posture decoding can significantly improve the pelvis forward angle and lumbar motion of LCS patients, relieving back pain and relaxing back muscles.

Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial-lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy.

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

Objective    To investigate the clinical efficacy of unilateral antegrade selective cerebral perfusion (UASCP) compared to bilateral antegrade selective cerebral perfusion (BASCP) in aortic surgery. Methods    PubMed, EBSCO, Web of Science, Cochrane Library, CBM, CNKI, Wanfang Database were searched from establishment of each database to January 2019 to identify clinical studies on prognosis of UASCP versus BASCP in aortic surgery patients. The quality of randomized controlled trials was assessed by Cochrane risk assessement tool. The quality of non-randomized controlled trials was assessed by the Newcastle-Ottawa Scale ( NOS). Meta-analyses were presented in terms of odds ratio (OR) with 95% confidence interval (CI) by using RevMan 5.3 software. Results    Sixteen eligible studies including 3 randomized controlled trials, 2 propensity matching score studies, and 11 retrospective case control studies including 4 490 patients were identified. The 3 randomized controlled trials were with high bias risk. The NOS score of the other 13 studies was more than 6 stars. Pooled analysis showed no significant difference between the UASCP and BASCP groups in terms of permanent neurological dysfunction (PND) (OR=0.93, 95%CI 0.74 to 1.18, P=0.57), temporary neurological dysfunction (TND) (OR=1.26, 95%CI 0.94 to 1.69, P=0.12), acute kidney injury rate (OR=1.11, 95%CI 0.79 to 1.55, P=0.55), 30-day mortality (OR=0.94, 95%CI 0.67 to 1.32, P=0.72), length of ICU stay (OR=–0.64, 95%CI –1.66 to 0.37, P=0.22) and hospital stay (OR=–0.35, 95%CI –2.38 to 1.68, P=0.74). Conclusion    This meta-analysis shows that UASCP and BASCP administration do not result in different mortality and neurologic morbidity rates. However, more studies with good methodologic quality and large sample are still needed to make further assessment.

The effect of methanol addition on the heterologous expression of isoprenyl transferase NovQ was studied in Pichia pastoris Gpn12, with menadione and isopentenol as precursors to catalyze vitamin K2 (MK-3) synthesis. The expression of NovQ increased by 36% when 2% methanol was added every 24 h. The influence of initial pH, temperature, methanol addition, precursors (menadione, isopentenol) addition, catalytic time and cetyltrimethyl-ammonium bromide (CTAB) addition were explored in the P. pastoris whole-cell catalytic synthesis process of MK-3 in shaking flask. Three significant factors were then studied by response surface method. The optimal catalytic conditions obtained were as follows: catalytic temperature 31.56 ℃, menadione 295.54 mg/L, catalytic time 15.87 h. Consistent with the response surface prediction results, the optimized yield of MK-3 reached 98.47 mg/L in shaking flask, 35% higher than that of the control group. On this basis, the production in a 30-L fermenter reached 189.67 mg/L when the cell catalyst of 220 g/L (dry weight) was used to catalyze the synthesis for 24 h. This method laid the foundation for the large-scale production of MK-3 by P. pastoris Gpn12.