To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

To introduce the general thinking,guidelines,work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition,and to summarize and figure out the main characteristics on dosage forms,physico-chemical testing,microbial and biological testing,ref-erence standards and guidelines.The newly revised general chapters of pharmacopoeia give full play to the norma-tive and guiding role of the Chinese Pharmacopoeia standard,track the frontier dynamics of international drug regu-latory science and the elaboration of monographs,expand the application of state-of-the-art technologies,and stead-ily promote the harmonization and unification with the ICH guidelines;further enhance the overall capacity of TCM quality control,actively implement the 3 R principles on animal experiments,and practice the concept of environ-mental-friendly;replace and/orreduce the use of toxic and hazardousreagents,strengthen the requirementsofdrug safety control.This paper aims to provide a full-view perspective for the comprehensive,correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective To analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate.Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system.A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration;using the substrate depletion method,the enzymatic reaction kinetics parameters of metoprolol tartrate(such as Vmax and Km).Series concentrations of famotidine were co-incubated with metoprolol tartrate,and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism.Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes,with an optimal protein concentration of 1.0 mg/mL.The enzymatic reaction kinetics parameters were Vmax=0.07 μmol/min/mg protein and Km=7.84 μmol/L.Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system,suggesting that the combination of these two drugs may be relatively safe.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective:To explore expression changes of different vascular endothelial growth factor A (VEGFA) isoforms in human retinal pigment epithelial cell line ARPE-19 cells under high glucose conditions.Methods:ARPE-19 cells were divided into blank control group, control group 1, control group 2, HG1 group, and HG2 group treated with 5.5 mmol/L glucose, 5.5 mmol/L glucose+ 19.5 mmol/L mannitol, 5.5 mmol/L glucose+ 44.5 mmol/L mannitol, 25.0 mmol/L glucose, and 50.0 mmol/L glucose, respectively.The blank control group, control group 1, and control group 2 were treated for 72 hours, while HG1 and HG2 groups were treated for 24, 48, and 72 hours.The relative expression of VEGFA isoforms was detected by fluorescent quantitative PCR.Total VEGFA, SERPINF1 (pigment epithelium-derived factor, PEDF), a negative regulator of VEGF signaling, and VEGF165 (V4, 5, 10) protein expression was measured by Western blot.Results:Total VEGFA mRNA and protein expression in ARPE-19 cells showed statistically significant differences at both 25 mmol/L and 50 mmol/L glucose concentrations across different culture periods (mRNA: F=114.60, 143.60; both P<0.05.protein: F=10.00, 8.04; both P<0.05). Compared to the respective controls, the relative expression of total VEGFA mRNA and protein increased significantly at 24, 48, and 72 hours after treatment (all P<0.05). There was no significant difference in SERPINF1 (PEDF) mRNA or protein expression in ARPE-19 cells across different time points at 25 mmol/L or 50 mmol/L glucose concentrations (mRNA: F=0.86, 0.32; both P>0.05.protein: F=1.25, 0.08; both P>0.05). The mRNA expression levels of VEGFA isoforms in ARPE-19 cells from highest to lowest were VEGF165(V4, 5, 10), VEGF121(V6), VEGF189(V2), VEGF111(V8) and VEGF165b(V7). The relative VEGF111(V8) mRNA expression level was significantly lower in HG1-24 hour group than in control group 1, the relative VEGF189(V2) and VEGF121(V6) mRNA expression levels were significantly higher in HG1-48 hour group than in control group 1, the relative VEGF121(V6) and VEGF165b(V7) mRNA expression levels were significantly higher in HG1-72 hour group than in control group 1, with statistically significant differences (all P<0.05). The relative VEGF111(V8) and VEGF165(V4, 5, 10) mRNA expression levels were significantly higher in the HG2-24 hour group than in control group 2, the relative VEGF165(V4, 5, 10) and VEGF165b(V7) mRNA expression levels were significantly higher in HG2-48 hour group than control group 2, and the relative VEGF189(V2), VEGF111(V8), VEGF165(V4, 5, 10), and VEGF165b(V7) mRNA expression levels were significantly higher in HG2-72 hour group than in control group 2, with statistically significant differences (all P<0.05). The relative VEGF165(V4, 5, 10) protein expression levels in blank control group, control group 1, HG1-24 hour group, HG1-48 hour group, and HG1-72 hour group were 1.01±0.07, 1.05±0.07, 1.16±0.06, 1.37±0.08, and 1.28±0.05, respectively, with a statistically significant overall difference ( F=10.36, P<0.05). The relative VEGF165(V4, 5, 10) protein expression level was significantly higher in HG1-48 hour group than in control group 1 ( P<0.05). The relative protein expression levels of VEGF165(V4, 5, 10) in blank control group, control group 2, HG2-24 hour group, HG2-48 hour group, and HG2-72 hour group were 1.02±0.05, 1.12±0.00, 1.22±0.05, 1.53±0.21, and 1.77±0.04, respectively, with a statistically significant overall difference ( F=16.55, P<0.001). The relative VEGF165(V4, 5, 10) protein levels were significantly higher in HG2-48 hour group and HG2-72 hour group than in control group 2 (both P<0.05). Conclusions:In ARPE-19 cells, mRNA abundance of VEGFA isoforms from highest to lowest were VEGF165(V4, 5, 10), VEGF121(V6), VEGF189(V2), VEGF111(V8), VEGF165b(V7). VEGF121(V6) mRNA expression level is significantly increased at 25 mmol/L high glucose concentration, whereas VEGF165(V4, 5, 10) mRNA expression level shows significant elevation only at 50 mmol/L high glucose.Under both high glucose conditions, isoforms with significantly elevated mRNA expression levels are VEGF189(V2) and VEGF165b(V7), while SERPINF1 (PEDF) expression level does not change significantly.

Objective To investigate the effects of two driving pressure-based methods to set positive end-expiratory pressure on pulmonary mechanics and oxygenation in patients undergoing laparoscopic and thoracoscopic esophagectomy.Methods Sixty patients undergoing laparoscopic and thoracoscopic esophagectomy were divided into two groups(n=30 each):incremental group(group Ⅰ)and decremental group(group D).PEEP titration was performed in both groups during thoracoscopy and laparoscopy.Respiratory mechanics parameters,hemodynamic parameters,and blood gas analysis were collected for analysis before preoxygenation(T0),10 minutes after intuba-tion(T1),20 minutes after PEEP application for one-lung ventilation(T2),20 minutes after PEEP application for two-lung ventilation(T3),before extubation(T4),and 30 minutes after extubation(Ts).The postoperative pulmonary complications within 3 days and 7 days after operation,hospitalization duration,and costs were recorded.Results Compared with group Ⅰ,patients in group D showed higher oxygenation index and pulmonary compliance during surgery(P＜0.05).In both groups,driving pressure decreased and compliance increased after PEEP titration(P＜0.05).Conclusion Both driving pressure-guided incremental and decremental titration of individualized PEEP improved intraoperative respiratory mechanics in patients undergoing laparoscopic and thoracoscopic esopha-gectomy,and decremental titration was more effective in improving intraoperative respiratory mechanics and oxygenation in patients during operation.

Objective:To explore expression changes of different vascular endothelial growth factor A (VEGFA) isoforms in human retinal pigment epithelial cell line ARPE-19 cells under high glucose conditions.Methods:ARPE-19 cells were divided into blank control group, control group 1, control group 2, HG1 group, and HG2 group treated with 5.5 mmol/L glucose, 5.5 mmol/L glucose+ 19.5 mmol/L mannitol, 5.5 mmol/L glucose+ 44.5 mmol/L mannitol, 25.0 mmol/L glucose, and 50.0 mmol/L glucose, respectively.The blank control group, control group 1, and control group 2 were treated for 72 hours, while HG1 and HG2 groups were treated for 24, 48, and 72 hours.The relative expression of VEGFA isoforms was detected by fluorescent quantitative PCR.Total VEGFA, SERPINF1 (pigment epithelium-derived factor, PEDF), a negative regulator of VEGF signaling, and VEGF165 (V4, 5, 10) protein expression was measured by Western blot.Results:Total VEGFA mRNA and protein expression in ARPE-19 cells showed statistically significant differences at both 25 mmol/L and 50 mmol/L glucose concentrations across different culture periods (mRNA: F=114.60, 143.60; both P<0.05.protein: F=10.00, 8.04; both P<0.05). Compared to the respective controls, the relative expression of total VEGFA mRNA and protein increased significantly at 24, 48, and 72 hours after treatment (all P<0.05). There was no significant difference in SERPINF1 (PEDF) mRNA or protein expression in ARPE-19 cells across different time points at 25 mmol/L or 50 mmol/L glucose concentrations (mRNA: F=0.86, 0.32; both P>0.05.protein: F=1.25, 0.08; both P>0.05). The mRNA expression levels of VEGFA isoforms in ARPE-19 cells from highest to lowest were VEGF165(V4, 5, 10), VEGF121(V6), VEGF189(V2), VEGF111(V8) and VEGF165b(V7). The relative VEGF111(V8) mRNA expression level was significantly lower in HG1-24 hour group than in control group 1, the relative VEGF189(V2) and VEGF121(V6) mRNA expression levels were significantly higher in HG1-48 hour group than in control group 1, the relative VEGF121(V6) and VEGF165b(V7) mRNA expression levels were significantly higher in HG1-72 hour group than in control group 1, with statistically significant differences (all P<0.05). The relative VEGF111(V8) and VEGF165(V4, 5, 10) mRNA expression levels were significantly higher in the HG2-24 hour group than in control group 2, the relative VEGF165(V4, 5, 10) and VEGF165b(V7) mRNA expression levels were significantly higher in HG2-48 hour group than control group 2, and the relative VEGF189(V2), VEGF111(V8), VEGF165(V4, 5, 10), and VEGF165b(V7) mRNA expression levels were significantly higher in HG2-72 hour group than in control group 2, with statistically significant differences (all P<0.05). The relative VEGF165(V4, 5, 10) protein expression levels in blank control group, control group 1, HG1-24 hour group, HG1-48 hour group, and HG1-72 hour group were 1.01±0.07, 1.05±0.07, 1.16±0.06, 1.37±0.08, and 1.28±0.05, respectively, with a statistically significant overall difference ( F=10.36, P<0.05). The relative VEGF165(V4, 5, 10) protein expression level was significantly higher in HG1-48 hour group than in control group 1 ( P<0.05). The relative protein expression levels of VEGF165(V4, 5, 10) in blank control group, control group 2, HG2-24 hour group, HG2-48 hour group, and HG2-72 hour group were 1.02±0.05, 1.12±0.00, 1.22±0.05, 1.53±0.21, and 1.77±0.04, respectively, with a statistically significant overall difference ( F=16.55, P<0.001). The relative VEGF165(V4, 5, 10) protein levels were significantly higher in HG2-48 hour group and HG2-72 hour group than in control group 2 (both P<0.05). Conclusions:In ARPE-19 cells, mRNA abundance of VEGFA isoforms from highest to lowest were VEGF165(V4, 5, 10), VEGF121(V6), VEGF189(V2), VEGF111(V8), VEGF165b(V7). VEGF121(V6) mRNA expression level is significantly increased at 25 mmol/L high glucose concentration, whereas VEGF165(V4, 5, 10) mRNA expression level shows significant elevation only at 50 mmol/L high glucose.Under both high glucose conditions, isoforms with significantly elevated mRNA expression levels are VEGF189(V2) and VEGF165b(V7), while SERPINF1 (PEDF) expression level does not change significantly.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.