Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Objective To investigate the effect of differentdoses of oxycodone on postoperative recovery quality in elderly patients undergoing laparoscopic cholecystectomy.Methods Elderly patients scheduled for elective laparoscopic cholecystectomy at Mianyang Central Hospital from September 2023 to April 2024 were selected.Patients were randomly divided into group C,group O1 and group O2.Ten minutes before anesthesia induction,group O1 received intravenous oxycodone 0.05 mg·kg-1,group O2 received oxycodone 0.1 mg·kg-1,and group C received an equivalent volume of 0.9%sodium chloride.Observe and compare the scores of the Quality of Recovery-40(QoR-40)scale at 24 hours postoperatively,the Visual Analogue Scale(VAS)for pain at 10 minutes postoperatively and incidence of postoperative respiratory amnesia among the three groups.Multiple linear regression analysis was used to investigate the effect of hydrocodone on postoperative QoR-40 score.Results A total of 117 patients were included,39 in each group.According to the dropout criteria,a total of 34 cases were included in the group C,38 cases in group O1,and 38 cases in group O2.Compared to group C,group O1 and O2 showed significantly higher QoR-40 scores at 24 hours postoperatively(P<0.01),particularly in physical comfort,emotional state,independent functioning,and pain(P<0.05 or P<0.01).However,there was no significant difference between group O1 and O2(P>0.05).Both oxycodone groups had significantly lower 10-minute postoperative VAS scores than group C(P<0.05).Group O1 had a lower incidence of respiratory amnesia than group O2(P<0.05).Multivariate regression revealed that oxycodone use,age,postoperative nausea/vomiting,and 10-minute VAS scores collectively explained 69%of the variance in QoR-40 scores at postoperatively(adjusted R2=0.69),with oxycodone use significantly improving QoR-40 scores at postoperatively[β=9.336,95%CI(7.428,11.243),P<0.001].Conclusion Preoperative intravenous administration of oxycodone improves the quality of recovery in elderly patients after laparoscopic cholecystectomy.The incidence of postoperative respiratory amnesia was lower in 0.05 mg·kg-1 oxycodone dose group.

Objective To investigate the effect of intravenous flurbiprofen axetil on the incidence and severity of catheter-related bladder discomfort(CRBD)after transurethral resection of the prostate(TURP).Methods The elderly patients undergoing TURP under general anesthesia were enrolled,and randomly divided into two groups:flurbiprofen axetil group(group F)and control group(group C).Ten minutes before the end of surgery,group F was given 50 mg of flurbiprofen axetil intravenously,group C was given an equal amount of 0.9％sodium chloride injection.The primary outcome indicator was the incidence of moderate to severe CRBD immediately after entering the resuscitation room(T0).Secondary indicators included the incidence and severity of CRBD at 1 h(T1),2 h(T2),and 6 h(T3)after entering the resuscitation room,the amount of sufentanil used within 24 hours after surgery,postoperative NRS score,flurbiprofen axetil-related and analgesic adverse reactions 24 hours after surgery,and patient satisfaction.Results A total of 90 patients were included and each group was 45 patients.The incidence of moderate to severe CRBD at T0 was significantly lower in group F than that in group C(8.9％vs.33.3％,P=0.004).The incidence of CRBD in T1,T2,and T3 was lower in group F than in group C(P＜0.05).The incidence of mild CRBD at T3 in group F was lower than that in group C(P＜0.05).The incidence of moderate to severe CRBD at T1 and T2 in groups F was lower than that in group C(P＜0.05).The amount of sufentanil used in group F at 24 hours after surgery was significantly lower than that in group C(P=0.001).The pain scores in group F at T0,T1,T2,and T3 were lower than those in group C(P＜0.05);The postoperative patient satisfaction score in group F was higher than that in group C(P=0.001).However,there were no significant differences between the two groups in postoperative anesthesia resuscitation time and 24-hour adverse reactions incidence(P＞0.05).Conclusion Intravenous flurbiprofen axetil can safely and effectively reduce the incidence and severity of CRBD after TURP.It can significantly relieve pain,reduce sufentanil use,and have high clinical application value.

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

Biomanufacturing has emerged as a crucial driving force for efficient material conversion through engineered cells or cell-free systems. However, the intrinsic spatiotemporal heterogeneity, complexity, and dynamic characteristics of these processes pose significant challenges to systematic understanding, optimization, and regulation. This review summarizes essential methodologies for multi-omics data acquisition and analyses for bioprocesses and outlines modelling approaches based on multi-omics data. Furthermore, we explore practical applications of multi-omics and modelling in fine-tuning process parameters, improving fermentation control, elucidating stress response mechanisms, optimizing nutrient supplementation, and enabling real-time monitoring and adaptive adjustment. The substantial potential offered by integrating multi-omics with computational modelling for precision bioprocessing is also discussed. Finally, we identify current challenges in bioprocess optimization and propose the possible solutions, the implementation of which will significantly deepen understanding and enhance control of complex bioprocesses, ultimately driving the rapid advancement of biomanufacturing.
Fermentation ; Genomics/methods* ; Biotechnology/methods* ; Proteomics/methods* ; Models, Biological ; Metabolomics/methods* ; Bioreactors ; Multiomics

OBJECTIVE To observe the clinical efficacy of Shaoqi Yijia Prescription in the treatment of Hashimoto's thyroiditis(HT)with liver depression and spleen deficiency in the non-hypothyroidism stage and its effect on serum inflammatory factors.METHODS A total of 74 patients with Hashimoto's thyroiditis of liver depression and spleen deficiency type in the non-hypothyroid-ism stage who were treated in Putuo District Central Hospital in Shanghai from June to August 2024 were selected and randomly divided into the observation group and the control group with 37 cases in each group(2 cases dropped out in each group).The control group was treated with oral selenium yeast tablets,and the observation group was treated with Shaoqi Yijia Prescription,both for 12 weeks.The traditional Chinese medicine(TCM)syndrome scores,Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD)and fatigue self-assessment scale(FSAS)scores were evaluated before and after treatment;the thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb)and serum inflammatory factors interleukin 4(IL-4),IL-6,IL-10,TNF-α and IFN-γ levels were detected before and after treatment in the two groups of patients.RESULTS After treatment,the total score of TCM syndrome and the scores of epigastric or hypochondrium pain,abdominal distension,poor appetite,depression or irritability,and frequent sighs in the observation group were significantly reduced(P<0.05,P<0.01),and the total score of the observation group was better than that of the control group(P<0.01);after treatment,the serum TPOAb level of the observation group was significantly re-duced(P<0.05),the serum TPOAb level of the control group did not change significantly(P>0.05),and the serum TgAb and TPO-Ab levels of the observation group were better than those of the control group(P<0.05);after treatment,the HAMA and HAMD scores of the observation group were significantly reduced(P<0.01),and the HAMA,HAMD and FSAS scores of the observation group were better than those of the control group(P<0.05);after treatment,the serum IL-4 and IL-10 levels of the observation group were in-creased(P<0.05),and the IL-6,IFN-γ and TNF-α levels were decreased compared with those before treatment(P<0.05).The se-rum IL-4,IL-6 and IL-10 levels of the observation group were significantly different from those of the control group(P<0.05).CONCLUSION Shaoqi Yijia Prescription can alleviate the clinical symptoms of patients with Hashimoto's thyroiditis of liver depres-sion and spleen deficiency type in the non-hypothyroid period,and improve anxiety and depression,which may be related to improving the body's inflammatory response.

Objective:To investigate the clinical characteristics and risk factors for recurrence of perianal abscess in children.Methods:A retrospective study was conducted on the clinical data of 161 children with perianal abscess who were hospitalized in the Children's Hospital affiliated to Zhengzhou University from January 2015 to December 2022.Based on whether or not recurrence occurred after treatment，the patients were divided into the recurrence group(58 cases) and the simple group(103 cases).The clinical manifestations，laboratory examination indexes，and recurrence risk factors of children with perianal abscess were analyzed.Results:The effective rate of treatment for 161 children with perianal abscess was 64.0% (103/161),and 58 cases had recurrent abscess or fistula formation.The main orientations of the lesions were at the 3 o'clock position in 62 cases (38.5%) and at the 9 o'clock position in 67 cases (41.6%) in the lithotomy site.Bacterial culture of drainage fluid from perianal abscesses was positive in 61 (37.9%) children and the pathogens were Klebsiella pneumoniae in 48 cases,Staphylococcus aureus in 7 cases and Escherichia coli in 6 cases.The recurrence group mainly had underlying diseases including 38 cases of Crohn's disease，15 cases of chronic diarrhoea，and 5 cases of immunodeficiency,while the simple group had 3 cases of Crohn's disease，36 cases of chronic diarrhoea，and 2 cases of immunodeficiency，with 62 cases（60.1%）had no underlying diseases.The recurrence group showed significant statistical differences in gender（ χ2= 4.347， P=0.041），age（ χ2= 4.071， P=0.045），abscess size（ χ2= 6.298， P=0.008），abscess with fistula（ χ2= 10.928， P<0.001），combined with underlying diseases（ χ2= 10.673， P<0.001），fever（ χ2= 6.215， P=0.014），growth retardation（ χ2= 8.273， P=0.004），malnutrition（ χ2=4.521， P=0.038），hospitalization cost（ t=5.581， P=0.021），and hospital stay（ t=5.309， P=0.036）compared to the simple group.Additionally，the recurrence group showed significant statistical differences in white blood cells（ t=6.873， P=0.006），C-reactive protein（ t=7.631， P=0.003），fecal calprotectin（ t=10.073， P<0.001），albumin（ t=4.587， P=0.025），interleukin-6（ t=11.648， P<0.001），tumor necrosis factor-α（ t=7.803， P=0.021），lymphocyte count（ t=8.478， P=0.011），CD4 +/CD8 + ratio（ t=10.674， P<0.001），and IgA（ t=6.437， P=0.002）compared to the simple group.Multivariate Logistic regression analysis showed that abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 + ratio，and high fecal calprotectin were high risk factors for recurrence of perianal abscess in children. Conclusion:Children with perianal abscesses have a high recurrence rate and are prone to fistula formation.Perianal abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 +ratio，and high fecal calprotectin are high risk factors for recurrence in children.

Objective To investigate the effect of intravenous flurbiprofen axetil on the incidence and severity of catheter-related bladder discomfort(CRBD)after transurethral resection of the prostate(TURP).Methods The elderly patients undergoing TURP under general anesthesia were enrolled,and randomly divided into two groups:flurbiprofen axetil group(group F)and control group(group C).Ten minutes before the end of surgery,group F was given 50 mg of flurbiprofen axetil intravenously,group C was given an equal amount of 0.9％sodium chloride injection.The primary outcome indicator was the incidence of moderate to severe CRBD immediately after entering the resuscitation room(T0).Secondary indicators included the incidence and severity of CRBD at 1 h(T1),2 h(T2),and 6 h(T3)after entering the resuscitation room,the amount of sufentanil used within 24 hours after surgery,postoperative NRS score,flurbiprofen axetil-related and analgesic adverse reactions 24 hours after surgery,and patient satisfaction.Results A total of 90 patients were included and each group was 45 patients.The incidence of moderate to severe CRBD at T0 was significantly lower in group F than that in group C(8.9％vs.33.3％,P=0.004).The incidence of CRBD in T1,T2,and T3 was lower in group F than in group C(P＜0.05).The incidence of mild CRBD at T3 in group F was lower than that in group C(P＜0.05).The incidence of moderate to severe CRBD at T1 and T2 in groups F was lower than that in group C(P＜0.05).The amount of sufentanil used in group F at 24 hours after surgery was significantly lower than that in group C(P=0.001).The pain scores in group F at T0,T1,T2,and T3 were lower than those in group C(P＜0.05);The postoperative patient satisfaction score in group F was higher than that in group C(P=0.001).However,there were no significant differences between the two groups in postoperative anesthesia resuscitation time and 24-hour adverse reactions incidence(P＞0.05).Conclusion Intravenous flurbiprofen axetil can safely and effectively reduce the incidence and severity of CRBD after TURP.It can significantly relieve pain,reduce sufentanil use,and have high clinical application value.