The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

OBJECTIVES: To analyze the potential causal relationship between gut microbiota and food allergy (FA) using two-sample Mendelian randomization (MR) methods. METHODS: Data from genome-wide association studies on gut microbiota and FA were utilized. MR analysis was conducted employing inverse variance weighting, MR-Egger regression, and weighted median methods to assess the causal relationship between gut microbiota and FA. Cochrane's Q test was used to evaluate heterogeneity of instrumental variables, MR-PRESSO analysis was conducted to test for outliers and pleiotropy, and MR-Egger regression was employed to assess horizontal pleiotropy. The "leave-one-out" method was used to evaluate the impact of removing individual single nucleotide polymorphisms on the causal relationship. RESULTS: Inverse variance weighting analysis revealed that the phylum Verrucomicrobia, family Verrucomicrobiaceae, order Verrucomicrobiales, genus Ruminococcaceae UCG013, and genus Akkermansia were negatively associated with FA (P<0.05). Sensitivity analyses confirmed the reliability of the findings, indicating no heterogeneity or pleiotropy present. CONCLUSIONS There is a causal relationship between gut microbiota and FA, with Verrucomicrobia, Verrucomicrobiaceae, Verrucomicrobiales, Ruminococcaceae UCG013, and Akkermansia potentially reducing the risk of developing FA. These findings provide potential targets for the treatment and prevention of FA; however, further research is needed to explore the specific mechanisms by which the microbiota influence FA.
Humans ; Mendelian Randomization Analysis ; Gastrointestinal Microbiome ; Food Hypersensitivity/microbiology* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective·[18F]F-FMISO and[18F]F-FLT are specific PET imaging agents for detecting the hypoxia microenvironment and cell proliferation,respectively.This study aims to visualize and monitor the impact of drug resistance in pancreatic cancer on the hypoxia microenvironment and cell proliferation through[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging,with the goal of providing a theoretical basis for clinical application.Methods·The CCK-8 assay was conducted to assess drug resistance in the PANC-1/R(PR)pancreatic cancer cell line compared to the parental PANC-1(P)cell line.Subcutaneous xenograft models of pancreatic cancer were established by injecting male BALB/c nude mice with pancreatic cancer cells into the left axillary subcutaneous region.Subgroups were treated with gemcitabine(GEM)chemotherapy starting on day 18(18D-G group)or day 12(12D-G group)after inoculation of tumor cells.[18F]F-FMISO and[18F]F-FLT PET/CT imaging were performed before and after treatment to obtain semi-quantitative parameters(maximum standardized uptake value,SUVmax).ΔSUVmax was calculated by using the following equation:ΔSUVmax=(SUVmax of second imaging-SUVmax of first imaging)/SUVmax of first imaging.Receiver operating characteristic(ROC)curves were used to determine the optimal threshold for the semi-quantitative parameters to assess pancreatic cancer drug resistance.Results·The CCK-8 assay confirmed that the PR cells exhibited high resistance to GEM,with a resistance index of 4.24(n=5).In vivo experiments showed that GEM chemotherapy significantly inhibited tumor growth and prolonged survival in the parental pancreatic cancer group(12D-G group,P=0.025),whereas GEM chemotherapy accelerated tumor growth and shortened survival(18D-G and 12D-G,P=0.025)in the drug-resistant pancreatic cancer group.In addition,in the non-chemotherapy group,ΔSUVmax-FLT might be negatively correlated with survival time,while in the chemotherapy group,both ΔSUVmax-FMISO and ΔSUVmax-FLT were negatively correlated with survival time(P=0.050,P=0.006).In the 18D-G and chemotherapy group,the second imaging showed significantly lower ΔSUVmax-FMISO and ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.045,P=0.050).In the 12D-G and chemotherapy group,the second imaging showed slightly lower ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.051).ROC analysis identified the optimal threshold for assessing pancreatic cancer drug resistance:when ΔSUVmax-FLT=0.45 in the non-chemotherapy group,the sensitivity and specificity were 100.00%and 50.00%,respectively;when ΔSUVmax-FMISO=0.37 and ΔSUVmax-FLT=0.36 in the chemotherapy group,the sensitivity and specificity were 100.00%and 83.33%,respectively.Conclusion·[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging can be used to assess drug resistance in pancreatic cancer.The comparison of[18F]F-FMISO and[18F]F-FLT PET differences before and after chemotherapy provides the most accurate prediction of drug resistance and survival time.

Objective:To explore the application effect of continuous intravenous infusion of lidocaine on patients undergoing transnasal pituitary tumor resection.Methods:Ninety patients undergoing transsphenoidal pituitary tumor resection under general anesthesia from May 2022 to January 2025 were selected.The participants were randomly divided into two groups:a control group and a lidocaine group,with 45 patients in each group.Before starting anesthesia,the lidocaine group received intravenous injection of 1.5 mg/kg lidocaine,followed by continuous intravenous injection at a rate of 2 mg/(kg·h)throughout the entire surgical process.The control group received an equal amount of physiological saline.The other anesthesia regimens and drugs for the two groups of patients were consistent,and all anesthesia related drugs were stopped from infusion at the end of the surgery.Compare the intraoperative mean arterial pressure(MAP)and heart rate changes between two groups,evaluate visual analog scale(VAS)scores at different time points,postoperative opioid dosage and recovery level,and incidence of adverse reactions.Results:There was a certain degree of fluctuation in MAP and heart rate in both groups during the operation,with the lidocaine group showing a smaller level of fluctuation.There was no significant difference in MAP and heart rate levels between the two groups at T1 and T6 times(P＞0.05),while the MAP and heart rate levels in the lidocaine group were higher than those in the control group at T2,T3,T4,and T5 times(P＜0.05);Compared with the control group,there was no statistically significant difference in VAS scores between the two groups at T0 time(P＞0.05).The VAS scores of the two groups showed an upward trend at T1,T2,T3,and T4 time,and a downward trend at T5 time.However,the VAS scores of the lidocaine group were lower than those of the control group at T1,T2,T3,T4,and T5 time(P＜0.05);The dose of remifentanil administered via intravenous pump during the lidocaine group,the duration of first postoperative ventilation,and the length of hospital stay were all lower than those in the control group(P＜0.05);The incidence of nausea,vomiting,and coughing related adverse reactions in the lidocaine group was lower than that in the control group(P＜0.05).Conclusion:Lidocaine assisted intravenous anesthesia can promote stable hemodynamic fluctuations during pituitary adenoma resection surgery,reduce postoperative pain,decrease opioid dosage,shorten hospital stay,and reduce adverse reactions such as coughing,nausea,and vomiting.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To explore the application effect of continuous intravenous infusion of lidocaine on patients undergoing transnasal pituitary tumor resection.Methods:Ninety patients undergoing transsphenoidal pituitary tumor resection under general anesthesia from May 2022 to January 2025 were selected.The participants were randomly divided into two groups:a control group and a lidocaine group,with 45 patients in each group.Before starting anesthesia,the lidocaine group received intravenous injection of 1.5 mg/kg lidocaine,followed by continuous intravenous injection at a rate of 2 mg/(kg·h)throughout the entire surgical process.The control group received an equal amount of physiological saline.The other anesthesia regimens and drugs for the two groups of patients were consistent,and all anesthesia related drugs were stopped from infusion at the end of the surgery.Compare the intraoperative mean arterial pressure(MAP)and heart rate changes between two groups,evaluate visual analog scale(VAS)scores at different time points,postoperative opioid dosage and recovery level,and incidence of adverse reactions.Results:There was a certain degree of fluctuation in MAP and heart rate in both groups during the operation,with the lidocaine group showing a smaller level of fluctuation.There was no significant difference in MAP and heart rate levels between the two groups at T1 and T6 times(P＞0.05),while the MAP and heart rate levels in the lidocaine group were higher than those in the control group at T2,T3,T4,and T5 times(P＜0.05);Compared with the control group,there was no statistically significant difference in VAS scores between the two groups at T0 time(P＞0.05).The VAS scores of the two groups showed an upward trend at T1,T2,T3,and T4 time,and a downward trend at T5 time.However,the VAS scores of the lidocaine group were lower than those of the control group at T1,T2,T3,T4,and T5 time(P＜0.05);The dose of remifentanil administered via intravenous pump during the lidocaine group,the duration of first postoperative ventilation,and the length of hospital stay were all lower than those in the control group(P＜0.05);The incidence of nausea,vomiting,and coughing related adverse reactions in the lidocaine group was lower than that in the control group(P＜0.05).Conclusion:Lidocaine assisted intravenous anesthesia can promote stable hemodynamic fluctuations during pituitary adenoma resection surgery,reduce postoperative pain,decrease opioid dosage,shorten hospital stay,and reduce adverse reactions such as coughing,nausea,and vomiting.

Objective·[18F]F-FMISO and[18F]F-FLT are specific PET imaging agents for detecting the hypoxia microenvironment and cell proliferation,respectively.This study aims to visualize and monitor the impact of drug resistance in pancreatic cancer on the hypoxia microenvironment and cell proliferation through[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging,with the goal of providing a theoretical basis for clinical application.Methods·The CCK-8 assay was conducted to assess drug resistance in the PANC-1/R(PR)pancreatic cancer cell line compared to the parental PANC-1(P)cell line.Subcutaneous xenograft models of pancreatic cancer were established by injecting male BALB/c nude mice with pancreatic cancer cells into the left axillary subcutaneous region.Subgroups were treated with gemcitabine(GEM)chemotherapy starting on day 18(18D-G group)or day 12(12D-G group)after inoculation of tumor cells.[18F]F-FMISO and[18F]F-FLT PET/CT imaging were performed before and after treatment to obtain semi-quantitative parameters(maximum standardized uptake value,SUVmax).ΔSUVmax was calculated by using the following equation:ΔSUVmax=(SUVmax of second imaging-SUVmax of first imaging)/SUVmax of first imaging.Receiver operating characteristic(ROC)curves were used to determine the optimal threshold for the semi-quantitative parameters to assess pancreatic cancer drug resistance.Results·The CCK-8 assay confirmed that the PR cells exhibited high resistance to GEM,with a resistance index of 4.24(n=5).In vivo experiments showed that GEM chemotherapy significantly inhibited tumor growth and prolonged survival in the parental pancreatic cancer group(12D-G group,P=0.025),whereas GEM chemotherapy accelerated tumor growth and shortened survival(18D-G and 12D-G,P=0.025)in the drug-resistant pancreatic cancer group.In addition,in the non-chemotherapy group,ΔSUVmax-FLT might be negatively correlated with survival time,while in the chemotherapy group,both ΔSUVmax-FMISO and ΔSUVmax-FLT were negatively correlated with survival time(P=0.050,P=0.006).In the 18D-G and chemotherapy group,the second imaging showed significantly lower ΔSUVmax-FMISO and ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.045,P=0.050).In the 12D-G and chemotherapy group,the second imaging showed slightly lower ΔSUVmax-FLT in P tumors compared to PR tumors(P=0.051).ROC analysis identified the optimal threshold for assessing pancreatic cancer drug resistance:when ΔSUVmax-FLT=0.45 in the non-chemotherapy group,the sensitivity and specificity were 100.00%and 50.00%,respectively;when ΔSUVmax-FMISO=0.37 and ΔSUVmax-FLT=0.36 in the chemotherapy group,the sensitivity and specificity were 100.00%and 83.33%,respectively.Conclusion·[18F]F-FMISO and[18F]F-FLT PET/CT dual-nuclide imaging can be used to assess drug resistance in pancreatic cancer.The comparison of[18F]F-FMISO and[18F]F-FLT PET differences before and after chemotherapy provides the most accurate prediction of drug resistance and survival time.