ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Objective To explore the differences in stress distribution and stability of the planta pedis in the patients with unilateral and bilateral plantar fasciitis(PF)through plantar stress and center of pressure(COP)analysis.Methods A total of 100 patients with PF visiting in this hospital were enrolled,among them 50 cases were unilateral heel pain(unilateral heel pain group)and 50 cases were bilateral heel pain(bilateral heel pain).Meanwhile,50 healthy subjects were included(healthy group).In the health group and bilateral heel pain groups,the average stress value of both planta pedis surfaces of each subject was taken and named as the J0 group and H2 group,respectively.In the unilateral heel pain group,the plantar stress in 50 healthy feet and 50 affected feet were named as the J1 group and H1 group,respectively.The plantar pedis was divided into 10 regions for analysis and comparison[the first foot toe(T1),T2-5,the first-fifth metatarsal bones(M1-M5),the mid foot(MF),heel medial side(MH),heel lateral side(LH)].The subjects in 3 groups conducted the static and dynamic tests respectively,and the differences in plantar stress distribution and COP parameters among the J1,H1,H2 and J0 groups were compared respectively.Results In the static tests,the maximum pressure of the LH regions in the group J1 was increased when compared with the group J0,the contact area of LH regions in the group H1 was reduced when compared with the group J0,the maximum pressure of the M2 and M3 regions in the H1 group was increased when compared with the group J0,the contact areas of the MH and LH regions in the H2 group were decreased when compared with the group J0,the maximum pressure of the M1 region was increased when compared with the group J0,and the differences were statistically significant(P<0.05).In the dynamic tests,the maximum pressure of the T2-5 regions in the J1 group was increased when compared with the J0 group,the maximum pressure of the M3 region in the group H1 was increased when compared with the group J0,the maximum pressure of the M3 and M4 region in the group H2 was in-creased when compared with the group J0,and the differences were statistically significant(P<0.05).The COP 95%confidence ellipse area in the health group was the smallest,followed by the bilateral heel pain group,and finally the unilateral heel pain group,and the differences among 3 groups were statistically signifi-cant(P<0.05),there was also statistically significant difference between pairwise comparisons in 3 groups(P<0.05).Conclusion In the static condition,the pressure of the healthy heel and affected forefoot in the patients with PF is increased;while in the dynamic condition,the pressure of the toes of the healthy foot and forefoot of the affected foot in the patients with PF is also increased.The distribution of plantar stress in the patients with PF has larger difference compared with the healthy population,and the stability is poor.Meas-ures can be taken to improve the abnormal force on the foot,reduce pain and reduce the risk of falling.

[Objective] To explore the key factors affecting the efficiency and safety of hematopoietic stem cell apheresis. [Methods] The clinical data of 59 healthy donors who underwent allogeneic hematopoietic stem cell donation in the First Affiliated Hospital of Anhui Medical University from January 2021 to June 2024 were retrospectively analyzed. The number of CD34⁺ cells was used to evaluate the eligibility of stem cell collection. The effects of donor gender, age, patient weight, as well as the number of WBC, MNC, RBC, Hb, HCT, PLT, CD34⁺ cells, CD34⁺ percentage and instrument operating parameters on collection efficiency were analyzed. [Results] A total of 59 donors were enrolled, and 68 occasions of stem cell apheresis were performed, with a qualified collection rate of 56%. Donor gender, age, patient weight, total blood circulation volume, anticoagulant dosage, collection time, calcium gluconate dosage and RBC, Hb, HCT levels were not significantly correlated with the collection effect (P>0.05). Multivariate logistic regression analysis showed that the number of MNC cells, CD34⁺ cells and stem cell product volume were the key factors affecting the efficiency and safety. A total of 12 donors had mild adverse reactions during the collection process, and all of them were improved after treatment. [Conclusion] Optimizing apheresis strategy based on the three factors of MNC, WBC count and stem cell product volume on the day of collection will help to achieve high-quality collection and improve the success rate of transplantation.

BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

Objective: To explore the efficacy of vonoprazan fumarate in the treatment of laryngopharyngeal reflux disease（LPRD） evaluated by the Chinese version of the RSS-12 scale. Methods:A total of 100 LPRD patients treated in the otolaryngology-head and neck surgery outpatient clinic of our hospital were randomly divided into two groups（50 cases each）. The observation group was treated with vonoprazan fumarate（20 mg, once daily）, and the control group was treated with esomeprazole enteric-coated capsules（20 mg, twice daily） for 12 weeks. The selected observation indicators in this study included RSI, the Chinese version of RSS-12, and RFS scores before and after treatment. Results:Prior to treatment, there was no statistically significant difference in the Chinese version of RSS-12, RSI, and RFS between the two groups（P>0.05）. After 8 and 12 weeks of antacid treatment, both the Chinese version of RSS-12 and RSI significantly decreased in both group （P<0.05）. The changes in symptoms were particularly noticeable between 0-8 weeks of treatment according to the Chinese version of RSS-12 and RSI. After 12 weeks of treatment, the RFS scores significantly decreased compared to pretreatment levels （P<0.05）. After 12 weeks of antacid treatment, according to the Chinese version of RSS-12, 80% of patients in the observation group showed a good therapeutic response, compared to 64% in the control group; according to RSI, 90% of patients in the observation group showed a good therapeutic response, compared to 84% in the control group. There was no statistically significant difference in the treatment effect between the two groups after 12 weeks of treatment（P>0.05）. Conclusion:Vonoprazan fumarate can significantly improve the symptoms and signs of laryngopharyngeal reflux, and their treatment effect is not inferior to proton pump inhibitors. Compared with RSI, the Chinese version of RSS-12 can serve as a new screening tool for clinical diagnosis of LPRD in China.
Humans ; Sulfonamides/therapeutic use* ; Male ; Pyrroles/therapeutic use* ; Female ; Laryngopharyngeal Reflux/drug therapy* ; Treatment Outcome ; Middle Aged ; Esomeprazole/therapeutic use* ; Proton Pump Inhibitors/therapeutic use* ; Adult

OBJECTIVE: To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis. METHODS: A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis. RESULTS: A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)]. CONCLUSIONS The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans ; Retrospective Studies ; Male ; Sepsis ; Soft Tissue Infections/microbiology* ; Female ; Middle Aged ; Aged ; Adult ; Prognosis ; Risk Factors ; Necrosis ; Logistic Models ; Fasciitis, Necrotizing

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.