ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Objective To determine the optimal extraction process for kaempferol from Alpinia officinarum Hance and to investigate its antioxidant activity.Methods Based on single-factor experimental data,this study employed the Box-Behnken central composite design and response surface methodology(RSM),combined with high-performance liquid chromatography(HPLC),to plot response surface and contour maps using kaempferol content as the response value.The optimal parameters for ethanol concentration,solid-liquid ratio,extraction time,and extraction temperature were selected.The antioxidant activity of kaempferol was comprehensively evaluated by calculating the radical scavenging rate using the DPPH radical scavenging assays.Results The optimal extraction conditions were determined to be an ethanol concentration of 84%,a solid-liquid ratio of 1∶80,an extraction time of 2 hours,and an extraction temperature of 82℃.Under these conditions,the kaempferol content extracted from Alpinia officinarum Hance reached 0.034 16%.In the DPPH radical scavenging assay,the extract showed a scavenging rate of 91.20%at a concentration of 1 mg/mL.Conclusion The optimized extraction process for kaempferol from Alpinia officinarum Hance was obtained using the Box-Behnken response surface design method,and this process is practical and feasible.The DPPH radical scavenging assay demonstrated that kaempferol from Alpinia officinarum Hance possesses antioxidant activity.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

This study aimed to elucidate the mechanism of action of metformin (MET) in inhibiting the malignant progression of hepatocellular carcinoma (HCC) by regulating the degradation of aldo-keto reductase family 1 member C3 (AKR1C3). The correlation between the sensitivity of different hepatocellular carcinoma cell lines to MET and their basal expression levels of AKR1C3 was firstly evaluated. MET was found to significantly reduce the level and accelerate the degradation rate of AKR1C3 protein by Western blot. The interaction between MET and AKR1C3 protein was confirmed by cellular thermal shift assay (CETSA). Proteasome inhibitor MG132 and the lysosomal inhibitor chloroquine (CQ) were used to screen the degradation pathway, and confirm, in combination with the HBSS starvation-induced autophagy model, that MET mediated the degradation of AKR1C3 through the autophagy lysosome pathway. Ubiquitylation assay showed that MET specifically enhanced the K63-linked polyubiquitylation modification of AKR1C3. Sequestosome 1 (SQSTM1/p62) knockdown, immunoprecipitation, and immunofluorescence co-localization analyses confirmed that the autophagy receptor p62 plays a key role in mediating MET-induced degradation of AKR1C3. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C was used to demonstrate that the regulatory effect of MET on AKR1C3 is independent of the classical AMPK signaling pathway. The experimental results showed that metformin promoted the ubiquitination modification of AKR1C3 by targeting AKR1C3, enhanced the binding of AKR1C3 to autophagy receptor p62, then degraded the AKR1C3 protein through selective autophagy-like pathway, and ultimately inhibited the malignant phenotypes of hepatocellular carcinoma cells, which is a regulatory mechanism free of the classical AMPK activation pathway of metformin.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

We retrospectively analyzed 8 patients who had been on hemodialysis for over 30 years from two dialysis centers in Dalian, China. A literature review was conducted by searching PubMed, CNKI, Wanfang databases,and Chinese Medical Journal Network for cases of patients on hemodialysis for over 30 years. The 8 patients had good baseline health, with chronic glomerulonephritis as the primary renal disease and no comorbidities before initiating dialysis. They started hemodialysis between 21 and 38 years of age, predominantly using arteriovenous fistulas for vascular access. Dialysis was regular and adequate (KT/V 1.23-1.88). Key laboratory parameters, including hemoglobin (88-118 g/L), albumin (27.7-39.7 g/L), calcium (1.88-2.55 mmol/L), and phosphate (0.76-1.99 mmol/L), were generally within target ranges. Body mass index ranged from 15.20 to 22.96 kg/m2. This literature review of the study included 12 case reports and 4 orginal articles. Factors influencing long-term survival included baseline health status, primary renal disease, absence of comorbidities before dialysis initiation, age at dialysis initiation, type of vascular access, dialysis adequacy, complication management, and medical support. Standardized management and timely correction of complications can significantly improve prognosis and enhance long-term survival in hemodialysis patients.

Objective:To explore the evaluation and relationship of hepatitis B virus(HBV)surface antigen(HBsAg)in clinical laboratory in different detection systems,further scientifically and reasonably to explain the test results for serving clinical practices.Methods:During the period from June 2021 to July 2022,100 425 specimens of patients with screened,suspected and confirmed HBV infections were collected from the clinical departments(mainly infectious hepatology)of Nanyang Central Hospital.Detection methodology included quantitative(electrochemiluminescence and chemiluminescence),qualitative(gold standard),semi-quantita-tive(ELISA),and highly sensitive HBV-DNA(RT-PCR)methods,and then analyzed the strengths and weaknesses and closeness be-tween each methodology.The relationship between the two Roche HBsAg detection systems was analyzed by correlation analysis.The HBsAg efficacy analysis was validated using Cut/Off value setting and detection limit,which in turn analyzed the distribution of false-positive and false-negative reporting models.Results:Detection results for low-and medium-concentration HBsAg showed a correla-tion between the electrochemical luminescence semi-quantitative method and ELISA method.ELISA method still had advantages in terms of sensitivity and specificity when detecting HBsAg,and there were no significant differences compared to domestic and interna-tional HBsAg quantitative detection systems.Performance validation conducted in accordance with the CNAS-GL038 document showed that the minimum detection limit for HBsAg calculated using the ELISA method in this laboratory was 0.1 U/ml.When the ROC curve Cut/Off value was set to 0.105,the area under the curve was the largest(AUC=0.986).Based on Roche's semi-quantitative electroche-miluminescence detection and patient medical history,in the common reporting model for hepatitis B five-item detection using ELISA method,HBsAg false positives occurred most frequently when HBsAg was positive alone,and HBsAg occurred most frequently in the false positive range when the OD value was less than 0.5.In ELISA method for detecting HBsAg,as the OD value increased from 0.01 to 0.10,the number of false-negative results also increased.Roche Elecsys HBsAg Ⅱ Quant Ⅱ and Elecsys HBsAg Ⅱ testing systems exhibited good linearity under certain conditions,with a ratio of approximately 1/0.18.In Elecsys HBsAg Ⅱ Quant Ⅱ detection sys-tem,the test results of HBsAg samples diluted 400 times were highly consistent with the original test results with a coefficient of deter-mination R2=0.993 8.Conclusion:There was a certain relationship between various detection systems of HBsAg at a suitable concen-tration.The detection of HBsAg by ELISA can meet the needs of clinical detection.

The grade of histological severity is a determining factor to evaluate the prognosis and survival rate in primary biliary cholangitis (PBC). However, liver biopsy is limited by sampling error, invasiveness, high cost, and poor compliance. Therefore, in order to overcome the limitations of liver biopsy, some non-invasive evaluation methods have been studied and applied to evaluate the progression of liver fibrosis in PBC. The prognostic score can be calculated using routine laboratory test results obtained at the time of diagnosis, which are characterized by their simplicity, affordability, ease of acquisition, and superior reproducibility. Recent studies have reported that the prognostic score can be employed as a non-invasive liver fibrosis model to diagnose the liver fibrosis stage in PBC and predict the transplant-free survival rate, in addition to being used to evaluate the patient prognosis and transplant-free survival (TFS). This paper reviews, summarizes, and explores the research progress of different prognostic scores as non-invasive liver fibrosis models via their diagnostic performance and predictive accuracy for PBC.

Objective:To establish a three-dimensional navigation process for design and resection of perforator flaps based on multi-detector computed tomography angiography (MDCTA) and to explore its clinical application effects.Methods:This study was a retrospective observational study. From January 2021 to October 2023, 7 patients and 6 patients with post-traumatic skin and soft tissue defects in extremity and conformed to the inclusion criteria were admitted to the Affiliated Hospital of Jiangsu University and Wuxi No. 9 People's Hospital, respectively. There were 8 males and 5 females, aged 21 to 68 years. Nine patients had wounds on the hand and 4 patients had wounds on the foot. The wound area after debridement ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. Through the three-dimensional navigation process based on MDCTA, 14 perforator flaps were designed and resected, including 11 free anterolateral thigh perforator flaps and 3 pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain, with flap size ranging from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Six wounds in the flap donor sites were directly sutured, and eight wounds in the flap donor sites were transplanted with skin grafts. The consistency of the location, type, and source of the perforators was compared between the preoperative navigation display and actual intraoperative detection. Immediately after surgery, the coverage of wound by the flap was evaluated according to the self-made criteria. The postoperative flap survival was observed. The occurrence of complications was observed during follow-up. At the last follow-up, the appearance of the flaps was observed, the blood supply of the flaps and the hand function of the 9 patients with hand trauma were evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the foot function of the 4 patients with foot trauma was assessed using the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scoring System.Results:The location, type, and source of the perforators displayed in preoperative navigation were consistent with the actual intraoperative detection. Immediately after surgery, the coverage of the wounds by 11 flaps was rated as excellent, and that of 3 flaps was rated as moderate. Postoperatively, 13 flaps survived completely, and 1 flap had partial necrosis, which healed after a full-thickness skin grafting from the thigh. Patients were followed up for 4 to 24 months postoperatively, one patient developed a hematoma under the flap, and one patient had local infection. At the last follow-up, the flaps of all patients were good in color and texture, and 5 patients with bloated flaps post operation had good appearance after thinning surgery; the blood supply was excellent in 12 flaps and was good in 2 flaps; among patients with hand trauma, the hand function was rated as excellent in 2 cases, good in 4 cases, and poor in 3 cases; among patients with foot trauma, the foot function was rated as excellent in 3 cases and good in 1 case.Conclusions:The three-dimensional navigation process for design and resection of perforator flaps based on MDCTA realizes precise evaluation of perforator vessels in flap donor sites and skin and soft tissue defects in the recipient sites. Guided by the three-dimensional navigation process, the application of free anterolateral thigh perforator flaps and pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain in repairing skin and soft tissue defects in extremity realizes precise surgery, reducing flap donor site injury and achieving excellent clinical outcomes.

Objective:To investigate the application value of photon-counting detector CT (PCD-CT) in preoperative identification of critical anatomical structures and surgical assessment in pancreatic cancer, and to compare its performance with conventional energy-integrating detector CT (EID-CT) in delineating tumor margins, vascular structures, and neural anatomy.Methods:This single-center retrospective matched case-control study included 25 patients with pathologically confirmed pancreatic ductal adenocarcinoma who underwent PCD-CT enhanced scanning and curative surgery at Peking Union Medical College Hospital between February and June 2025 (PCD-CT group). These patients were matched in a 1∶2 ratio to 50 patients who underwent EID-CT between January 2016 and December 2024 and subsequently received curative surgery (EID-CT group). Tumor boundary clarity, vascular visualization scores, and neural structure visibility were subjectively evaluated using the Likert scoring system. The assessed vessels included the celiac artery, common hepatic artery, superior mesenteric artery, splenic artery, portal vein, superior mesenteric vein, splenic vein, and pancreaticoduodenal arterial arcade. Imaging-based assessment of structural involvement was compared with intraoperative findings and pathological results to calculate diagnostic accuracy. Surgeons rated the usefulness of PCD-CT images for identifying key structures and determining resectability using a 5-point Likert scale. The Mann-Whitney U test was used for group comparisons of subjective scores, and categorical data were analyzed using the χ2 test or Fisher exact test. Results:The PCD-CT group showed significantly higher scores for tumor boundary clarity, vascular visualization, and neural structure detectability than those of the EID-CT group (all P<0.05). The accuracy of assessing superior mesenteric vein involvement was 96.0% (24/25) in the PCD-CT group and 72.0% (36/50) in the EID-CT group, with a significant difference ( χ2=6.00, P=0.014). Postoperative surgeon evaluations indicated that PCD-CT provided substantial assistance for both key structure identification [5 (5, 5)] and resectability assessment [5 (4, 5)]. Conclusion:PCD-CT demonstrates superior performance over EID-CT in preoperative delineation of tumor margins, vascular structures, and neural anatomy and in the assessment of structural involvement in pancreatic cancer. It provides valuable anatomical information to support preoperative evaluation and surgical decision-making.