The philosophy of “treating disease before its onset” is a fundamental concept of traditional Chinese medicine (TCM), permeating its diagnostic and therapeutic framework, and is central to clinical practice. However, current TCM diagnostic and treatment models for the “pre-disease to disease” window period face several limitations, including the lack of comprehensive clinical parameters, difficulties in characterizing and integrating heterogeneous multimodal data, and insufficient dynamic precision in interventions and efficacy evaluations. To address these issues, guided by Professor Candong Li’s theory of TCM stateology, this study focuses on integrating objective multimodal data. It proposes a new model for personalized TCM diagnosis and treatment targeting the “pre-disease to disease” window period. This approach first proposes the idea of restructuring the conceptual framework of “symptom” and integrating multi-source heterogeneous data at macroscopic, mesoscopic, and microscopic levels to form a three-dimensional assessment indicator system. By integrating graph neural networks, convolutional neural networks, attention mechanisms, and knowledge graph-guided weight allocation, this approach enables collaborative representation, alignment, and fusion of multi-source data. Subsequently, it plans to construct a multimodal fusion model at both feature and decision levels, in order to establish mappings between indicators and TCM state elements, and to screen key indicators characterizing pathological evolution during the window period. Furthermore, it proposes a technical path for enhancing model interpretability using methods such as SHapley Additive exPlanations (SHAP) and Ablation-CAM++. Finally, with state assessment as the core, it proposes the concept of constructing a dynamic evaluation method for individualized diagnosis and treatment based on time-series data analysis using algorithms such as long short-term memory (LSTM) networks and gated recurrent units (GRUs). Moreover, a causal inference framework and semi-supervised learning strategies are introduced to enable quantitative evaluation of individual intervention effects and to provide interpretable therapeutic feedback, forming a complete technical path from data representation and fusion, weight adjustment, and interpretability analysis, to dynamic diagnosis feedback. This study aims to address deficiencies in the current TCM diagnosis and treatment model during the “pre-disease to disease” window period and to provide an operational framework for the clinical practice of TCM’s “treating disease before its onset”.

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

Objective:To investigate the efficacy of two types of micro-focused ultrasound devices combined with botulinum toxin type A (BoNT-A) injection for facial rejuvenation.Methods:A retrospective study was conducted, including 60 female patients aged 28-70 (41.3±7.9) years, who received facial rejuvenation treatment at the Department of Plastic and Reconstructive Surgery, Zhongnan Hospital of Wuhan University, from April 2023 to April 2024. Patients were divided into two groups based on the treatment method: the control group (received only micro-focused ultrasound treatment, n=30) and the combined group (received both micro-focused ultrasound and BoNT-A injection, n=30). Additionally, patients were further categorized into four subgroups based on the type of micro-focused ultrasound device used: Peninsula Microultra? (PM) device group ( n=15), Intelligent Ultrasound? (IU) device group ( n=15), PM device + BoNT-A injection group ( n=15), and IU device + BoNT-A injection group ( n=15). The severity of facial wrinkles was assessed using the wrinkle severity rating scale (WSRS), the Merz aesthetic scale (MAS), and the global aesthetic improvement scale (GAIS) at baseline and 6 months post-treatment. Adverse event rates were also recorded. Results:At 6 months post-treatment, the combined group showed significantly lower WSRS and MAS scores than the control group (both P<0.001). No significant differences were found between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups regarding WSRS and MAS scores (all P>0.05). Self-reported GAIS improvement was 56.7% (17/30) for the control group and 80.0% (24/30) for the combined group, with the combined group showing superior results ( P=0.015). The physician-assessed GAIS improvement was 70.0% (21/30) for the control group and 96.7% (29/30) for the combined group, again with the combined group showing superior results ( P=0.007). No significant differences were found in self-reported or physician-assessed GAIS improvement between the PM and IU device groups, or between the PM + BoNT-A and IU + BoNT-A groups (all P>0.05). No severe adverse reactions, such as blisters, scabbing, purpura, bruising, scarring, peripheral facial paralysis, allergies, muscle weakness, dysphagia, or dysphonia, were observed in any patient. Conclusion:The combination of micro-focused ultrasound and BoNT-A injection for facial rejuvenation is more effective than micro-focused ultrasound alone, while there are no significant differences in efficacy between the two micro-focused ultrasound devices.

Objective:To investigate the predictive value of preoperative aspartate aminotransferase to alanine aminotransferase ratio (AAR) for early recurrence after radical resection of single small hepatocellular carcinoma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 137 patients who underwent radical resection of liver cancer at the General Hospital of Ningxia Medical University from January 2017 to July 2021. These patients were categorized into a recurrence group ( n = 72) and a non-recurrence group ( n = 65) based on early postoperative recurrence. Univariate and multivariate logistic regression analyses were conducted in the training cohort to identify independent risk factors for early recurrence of small hepatocellular carcinomas. Subsequently, the AARs were grouped, and patients with similar propensity scores estimated by the logistic model were matched 1:1 using the Propensity Score Match method with a caliper value of 0.02 to eliminate confounders. Logistic regression analysis was then repeated to assess the predictive value of the matched AAR for postoperative recurrence in patients with single small hepatocellular carcinoma. Results:Univariate analysis revealed that age ( χ2 = 4.22, P = 0.040), the ratio of fibrinogen to albumin ( χ2 = 8.26, P = 0.004), and the AAR ( χ2 = 5.83, P = 0.016) were significantly associated with early recurrence of small liver cancer after radical resection. Multivariate logistic regression analysis further identified age ( P = 0.042), the ratio of fibrinogen to albumin ( P = 0.024), and the AAR ( P = 0.018) as independent risk factors for early recurrence of single small hepatocellular carcinoma following radical surgery. After excluding confounding factors using the Propensity Score Match method, 25 patient pairs were successfully matched. Post-matching logistic regression analysis revealed that an AAR > 0.74 ( P = 0.005) and age > 60 years ( P = 0.024) were independent risk factors for early recurrence in patients with single small hepatocellular carcinoma following radical resection. Conclusion:Preoperative AAR is an independent risk factor for early recurrence in patients with single small hepatocellular carcinoma following surgery, demonstrating excellent predictive value.

Objective:To investigate the predictive values of clinical test indexes and imaging indexes for early postoperative recurrence of hepatitis B virus (HBV)-related small hepatocellular carcinoma.Methods:Clinical case data of 163 patients with HBV-related small hepatocellular carcinoma undergoing radical hepatectomy at the Department of Hepatobiliary Surgery in the General Hospital of Ningxia Medical University from January 2017 to August 2021 were retrospectively collected. The patients were categorized into 87 cases in an early recurrence group and 76 cases in a non-early recurrence group according to whether or not they had recurrence within 2 years after surgery. After excluding the covariance of various indicators, independent risk factors for postoperative tumor recurrence were established using univariate analysis and multivariate logistic regression analysis. A clinical prediction model was constructed and presented visually in a nomogram diagram, and the predictive ability of the nomogram diagram model was evaluated using receiver operating characteristic curves as well as calibration curves. Cox regression analysis was used to determine the relationship between independent risk factors and time to recurrence.Results:Univariate analysis showed that in the early recurrence group, the number and proportion of patients with preoperative gamma-glutamyl transferase to lymphocyte count ratio (GLR) > 35.79 [41.38% (36/87)], tumor multiplicity [25.29% (22/87)], the presence of peritumoral edema [45.98% (40/87)], intratumoral small arterial clusters [50.58% (44/87)], and age ≥ 60 years [74.71% (65/87)] were significantly higher than those in the non-early recurrence group ( χ2 = 5.73, 3.78, 3.97, 3.73, 3.75, all P < 0.05). Multivariate logistic regression analysis showed that GLR > 35.79 and the presence of peritumoral edema were independent risk factors for early recurrence after radical hepatectomy of HBV-related small hepatocellular carcinomas [odds ratio ( OR) = 2.22, 1.99, 95% confidence interval ( CI): 1.10-4.59, 1.00-3.99, P < 0.05]. The nomogram diagram prediction model was established, with a C index of 0.70 (95% CI: 0.60-0.79) in the receiver operating characteristic curve and a Brier Score of 0.22 in the calibration curve, which demonstrated good model differentiation and accuracy. Cox regression analysis showed that a GLR > 35.79 and the presence of peritumoral edema were risk factors affecting the time to recurrence after resection of HBV-associated small hepatocellular carcinomas. Conclusion:GLR > 35.79 and the presence of peritumoral edema are independent risk factors for early recurrence after radical hepatectomy of HBV-related small hepatocellular carcinoma. The constructed clinical prediction model has good predictive efficacy.

Objective: To study the effect of nonthermal argon atmospheric pressure plasma (NTAPP) treatment on the bonding strength between dentine and self-etch adhesive and the wettability of dentine surfaces under different treatment times. Methods: The plasma jet was operated at an input power of 9 W. Argon was used as the operating gas at a flow rate of 5 L/min. The dentin surface was exposed to the plasma jet (n=6) for various times (0, 5, 10, 15, 20 s). After a one-step self-etch adhesive (S3 Bond) was applied to the treated dentine surface, microtensile bonding specimens were made, and the microtensile bonding strength was tested. Then, the dentine surface contact angles were measured after NTAPP treatment for 5, 10, 15, and 20 s with the same gas flow rate and input power described above. Results: Along with the NTAPP treatment time, the dentin immediate bonding strength was significantly increased. The 15 s group showed significantly elevated bonding strength (31.82±2.80 MPa) in contrast to the other groups. The contact angles of each experimental group significantly decreased compared with the contact angles of the negative control group (75.57°±1.45°). The contact angles decreased the most to 33.56°±2.14° with NTAPP treatment for 15 s, and its wettability was the highest. Conclusion NTAPP treatment can significantly increase the wettability of the dentin surface and improve the adhesive strength of the adhesive interface with self-etching adhesive, which is also related to the treatment time.

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.