AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

The peripheral blood of healthy or ketosis dairy cows was collected,and CD4+T cells were isolated.The expressions of lipid synthesis related proteins fatty acid synthase(FASN),acetyl coenzyme A carboxylase 1(ACC1),cluster of differentiation 36(CD36)and store-operated calcium entry(SOCE)related proteins ORAIl,ORAI2,ORAI3,STIM1,STIM2 were detected by Western blot.IL-17 cells were detected by flow cytometry.CD4+T cells were isolated from the spleen of 1-day-old calves and cultured in vitro.Cells were treated and divided into control(Ctrl)group,si-lenced CD36(siCD36)group,stearic acid(SA)group,and SA+siCD36 group.Cells in the Ctrl and SA groups were transfected with 75 pmol/L negative control siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h;Cells in the siCD36 group and SA+siCD36 group were transfected with 75 pmol/L CD36 siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h in the SA+siCD36 group.The protein expression of FASN,CD36,ACC1,ORAI1,ORAI2,ORAI3,STIM1 and STIM2 was detected by Western blot,and IL-17 cells were detected by flow cytometry.The results showed that the expression of IL-17 in peripheral blood CD4+T cells of ketosis dairy cows was significantly increased compared to that of healthy cows(P＜0.01).Additionally,the protein level of FASN,CD36,STIM1(P＜0.05),and ACC1,ORAI2,ORAI3,STIM2(P＜0.01)were up-regulated.Compared with the Ctrl group,the protein expression levels of CD36,ACC1 and ORAI3(P＜0.05)were up-regulated in the SA group,as well as the protein expression of FASN and STIM1(P＜0.01).Additionally,the expression of IL-17 was significantly increased(P＜0.05).Compared with the SA group,there was a decrease in the protein expression of STIM1,ORAI1(P＜0.05)and CD36,ACC1,FASN,ORAI2(P＜0.01)in the siCD36+SA group,as well as IL-17(P＜0.05).These results suggest that SA can promote the expression of IL-17 in CD4+T cells in ketosis cows by regulating fatty acid synthesis and activating SOCE channels through CD36.

Guided by Zhang Zhongjing's axiom that"blood stasis induces water",this study develops stage-specific treatment strategies for edema in Kidney Consumption Disorder by examining its four-stage pathogenic progression:Sluggish Flow → Stagnant Obstruction → Depressed Accumulation → Stasis Congelation.We propose an integrated approach that reinforces the root by warming the kidney and replenishing essence,while addressing the branch by activating blood circulation and promoting diuresis.Stage-specific interventions include:for the Sluggish Flow Phase,warming and tonifying kidney Yang combined with unblocking Yang to promote uri-nation;for the Stagnant Obstruction Phase,warming the kidney and replenishing essence supported by activating blood circulation and freeing the collateral channels;for the Depressed Accumulation Phase,quickening blood and resolving stasis,regulating Qi and trans-forming turbidity,along with warming the kidney and strengthening essence;and for the Stasis Congelation Phase,expelling stagnant accumulations while simultaneously regulating essence and blood.This framework advances novel pattern-determined strategies for Kid-ney Consumption edema management.

Objective To establish a technical system for allogeneic kidney transplantation surgery in pigs using the Banna miniature pig inbred strain,and to evaluate it through routine blood tests,liver and kidney function tests,thus providing reference data for the preparation of allogeneic kidney transplantation models.Methods A total of 4 cases of allogeneic kidney transplantation surgeries were performed,including 1 case of single kidney transplantation in a healthy pig,2 cases of kidney transplantation after unilateral nephrectomy,and 1 case of kidney transplantation after bilateral nephrectomy.Before kidney transplantation,cross-matching and complement-dependent cytotoxicity(CDC)tests were used for matching between donor and recipient pigs.After kidney transplantation,peripheral blood samples were regularly collected from pigs for routine blood tests,liver function tests,and kidney function tests,and color Doppler ultrasound technology was used to detect blood supply to the transplanted kidneys.After reaching the experimental endpoint,both kidneys of pig DR1 and the left kidney of pig DR3 were collected and hematoxylin-eosin(HE)staining was performed to evaluate pathological changes in the transplanted kidneys.Results Recipient pigs DR1 and DR3 died at 17 days and 30 days after surgery respectively,while recipient pigs R and DR2 remained in good condition during the 30-day observation period.The results of liver and kidney function test showed that in pig DR1,alanine aminotransferase(ALT)levels increased on postoperative day 1(＞1 000 U/L),peaked on postoperative day 7(1 300 U/L),and aspartate aminotransferase(AST)levels peaked on postoperative day 1(＞3 000 U/L).On postoperative day 17,ALT and AST levels remained high(ALT,500 U/L;AST,700 U/L).In pigs R,DR2,and DR3,ALT and AST levels returned to normal around day 17.Serum creatinine(Crea)levels in pig R remained stable without postoperative increase.Crea levels in pigs DR1 and DR2 showed transient elevation on postoperative day 1,then gradually returned to normal(＜100 μmol/L).Crea levels in pig DR3 remained below 500 μmol/L from postoperative days 2-10,but increased between days 11-28,reaching up to 1 500 μmol/L,indicating gradual loss of kidney function.Ultrasound results showed that the preoperative resistive index(RI)of recipient pig R was 0.91.On postoperative day 24,renal cortex and medulla showed abundant blood flow signals with RI value of 0.88,which was close to the pre-transplantation RI value.For pig DR2,the RI value on postoperative day 17 was 0.89,with poor renal cortex blood flow and relatively good renal medulla blood flow.In pig DR1 on postoperative day 17,no blood flow signals were detected in the transplanted kidney.HE staining results showed that the non-transplanted healthy right kidney of pig DR1 had normal structure,while the transplanted left kidney showed blurred glomerular structure and nuclear dissolution,indicating that the left kidney had lost function before removal.In the transplanted left kidney of pig DR3,large numbers of red blood cells and lymphocyte infiltration were observed in glomeruli and renal tubules,indicating possible coagulation dysfunction and rejection reactions after kidney transplantation.Conclusion Banna miniature pig inbred strain is used as experimental animals to perform four cases of allogeneic pig-to-pig kidney transplantation.The physiological parameters of the recipient pig and the function of the transplanted kidney are monitored after surgery using routine blood tests,liver and kidney function tests,color Doppler ultrasound,and pathological examinations.The allogeneic pig-to-pig kidney transplantation technical system established in the study can provide a foundation for clinicians to conduct kidney transplantation surgeries.

AIM:To appraise the bioequivalence and safety of the test preparation of ritonavir tab-lets and the reference preparation(trade name:Norvir?)in healthy adult subjects under fasting and postprandial conditions.METHODS:This study was a randomized,open-label,single-dose,four-period,fully repeated crossover design bioequivalence study protocol.Thirty-six healthy male and female volunteers were enrolled in the fasting and post-prandial conditions,and a single dose of the test preparation and reference preparation was orally administered.We used liquid chromatography-tan-dem mass spectrometry(LC-MS/MS)to finish the bioassay of the drug concentration of ritonavir in plasma.Pharmacokinetic parameters were statisti-cally analyzed using PhoenixWinNonlin8.1 software(Pharsight,USA)and a non-compartmental model.RESULTS:Under fasting conditions,the pharmacoki-netic parameters of the test and reference prepara-tions:Cmax(792.010±369.282)ng/mL and(856.939±394.427)ng/mL,AUC0-t(6 463.043±2 876.849)ng·mL-1·h and(6 907.690±3 046.132)ng·mL-1·h,AUC0-∞(6 603.617±2 916.352)ng·mL-1·h and(7 051.614±3 093.047)ng·mL-1·h.Here are the pharmacokinetic parameters for both the test prep-aration and the reference preparation in the post-prandial condition:Cmax(574.380±289.566)ng/mL and(615.796±297.382)ng/mL,AUC0-t(5 084.796±2 435.557)ng·mL-1·h and(5 414.167±2 416.952)ng·mL-1·h,AUC0-∞(5 219.144±2 487.793)ng·mL-1·h and(5 551.060±2 490.604)ng·mL-1·h.The 90%confidence interval of the geometric mean ratio of AUC0-t,AUC0-∞,and Cmax for the test preparation and reference preparation lied in the equivalent range of statistics.CONCLUSION:The tested preparation was bioequivalent to the reference preparation un-der fasting and postprandial conditions.

Objective To compare the clinical efficacy of different urinary diversions,specifically exploring whether the flap embedding technique can improve bladder cancer patients'quality of life and reduce the incidence of related complications.Methods 63 bladder cancer patients undergoing radical cystectomy with urinary diver-sion,between December 2022 and December 2023,were divided into three groups:Ileal conduit group(n=21),flap embedding technique group(n=21),and traditional cutaneous ureterostomy group(n=21).General clini-cal data,surgical data,preoperative and postoperative renal function indicators,incidence of complications within 6 months postoperatively,and quality of life scores were compared among the groups.Results The operative time in the ileal conduit group was longer than that in the other two groups(P<0.05).The quality of life scores in the flap embedding technique group were superior to those in the traditional cutaneous ureterostomy group(P<0.05),but no significant difference was found compared to the ileal conduit group(P>0.05).In terms of postoperative complications,the incidence of intestinal obstruction in the flap embedding technique group was lower than that in the ileal conduit group(P<0.05),and the rate of reinsertion of a single-J stent for hydronephrosis in the flap embedding technique group was lower than that in the traditional cutaneous ureterostomy group(P<0.05).Postop-erative serum creatinine levels in the traditional cutaneous ureterostomy group were significantly higher than preop-erative levels(P<0.05),while no significant differences in renal function indicators were observed in the other two groups(P>0.05).Conclusion The flap embedding technique significantly improves patients'quality of life and reduces the incidence of postoperative complications.It is worthy of further promotion in clinical practice.

Objective To establish a technical system for allogeneic kidney transplantation surgery in pigs using the Banna miniature pig inbred strain,and to evaluate it through routine blood tests,liver and kidney function tests,thus providing reference data for the preparation of allogeneic kidney transplantation models.Methods A total of 4 cases of allogeneic kidney transplantation surgeries were performed,including 1 case of single kidney transplantation in a healthy pig,2 cases of kidney transplantation after unilateral nephrectomy,and 1 case of kidney transplantation after bilateral nephrectomy.Before kidney transplantation,cross-matching and complement-dependent cytotoxicity(CDC)tests were used for matching between donor and recipient pigs.After kidney transplantation,peripheral blood samples were regularly collected from pigs for routine blood tests,liver function tests,and kidney function tests,and color Doppler ultrasound technology was used to detect blood supply to the transplanted kidneys.After reaching the experimental endpoint,both kidneys of pig DR1 and the left kidney of pig DR3 were collected and hematoxylin-eosin(HE)staining was performed to evaluate pathological changes in the transplanted kidneys.Results Recipient pigs DR1 and DR3 died at 17 days and 30 days after surgery respectively,while recipient pigs R and DR2 remained in good condition during the 30-day observation period.The results of liver and kidney function test showed that in pig DR1,alanine aminotransferase(ALT)levels increased on postoperative day 1(＞1 000 U/L),peaked on postoperative day 7(1 300 U/L),and aspartate aminotransferase(AST)levels peaked on postoperative day 1(＞3 000 U/L).On postoperative day 17,ALT and AST levels remained high(ALT,500 U/L;AST,700 U/L).In pigs R,DR2,and DR3,ALT and AST levels returned to normal around day 17.Serum creatinine(Crea)levels in pig R remained stable without postoperative increase.Crea levels in pigs DR1 and DR2 showed transient elevation on postoperative day 1,then gradually returned to normal(＜100 μmol/L).Crea levels in pig DR3 remained below 500 μmol/L from postoperative days 2-10,but increased between days 11-28,reaching up to 1 500 μmol/L,indicating gradual loss of kidney function.Ultrasound results showed that the preoperative resistive index(RI)of recipient pig R was 0.91.On postoperative day 24,renal cortex and medulla showed abundant blood flow signals with RI value of 0.88,which was close to the pre-transplantation RI value.For pig DR2,the RI value on postoperative day 17 was 0.89,with poor renal cortex blood flow and relatively good renal medulla blood flow.In pig DR1 on postoperative day 17,no blood flow signals were detected in the transplanted kidney.HE staining results showed that the non-transplanted healthy right kidney of pig DR1 had normal structure,while the transplanted left kidney showed blurred glomerular structure and nuclear dissolution,indicating that the left kidney had lost function before removal.In the transplanted left kidney of pig DR3,large numbers of red blood cells and lymphocyte infiltration were observed in glomeruli and renal tubules,indicating possible coagulation dysfunction and rejection reactions after kidney transplantation.Conclusion Banna miniature pig inbred strain is used as experimental animals to perform four cases of allogeneic pig-to-pig kidney transplantation.The physiological parameters of the recipient pig and the function of the transplanted kidney are monitored after surgery using routine blood tests,liver and kidney function tests,color Doppler ultrasound,and pathological examinations.The allogeneic pig-to-pig kidney transplantation technical system established in the study can provide a foundation for clinicians to conduct kidney transplantation surgeries.

Objective To compare the clinical efficacy of different urinary diversions,specifically exploring whether the flap embedding technique can improve bladder cancer patients'quality of life and reduce the incidence of related complications.Methods 63 bladder cancer patients undergoing radical cystectomy with urinary diver-sion,between December 2022 and December 2023,were divided into three groups:Ileal conduit group(n=21),flap embedding technique group(n=21),and traditional cutaneous ureterostomy group(n=21).General clini-cal data,surgical data,preoperative and postoperative renal function indicators,incidence of complications within 6 months postoperatively,and quality of life scores were compared among the groups.Results The operative time in the ileal conduit group was longer than that in the other two groups(P<0.05).The quality of life scores in the flap embedding technique group were superior to those in the traditional cutaneous ureterostomy group(P<0.05),but no significant difference was found compared to the ileal conduit group(P>0.05).In terms of postoperative complications,the incidence of intestinal obstruction in the flap embedding technique group was lower than that in the ileal conduit group(P<0.05),and the rate of reinsertion of a single-J stent for hydronephrosis in the flap embedding technique group was lower than that in the traditional cutaneous ureterostomy group(P<0.05).Postop-erative serum creatinine levels in the traditional cutaneous ureterostomy group were significantly higher than preop-erative levels(P<0.05),while no significant differences in renal function indicators were observed in the other two groups(P>0.05).Conclusion The flap embedding technique significantly improves patients'quality of life and reduces the incidence of postoperative complications.It is worthy of further promotion in clinical practice.

BACKGROUND:Poly(lactic-co-glycolic acid)copolymer with good biosafety,biodegradability,and superior mechanical properties has become a focal point of research in stomatology.OBJECTIVE:To review the advance in stomatology of poly(lactic-co-glycolic acid)copolymer.METHODS:Using a computer-assisted search of relevant literature published in the China National Knowledge Infrastructure(CNKI)and PubMed databases,the search terms included"polylactic acid-hydroxyacetic acid,PLGA,oral defect,tissue engineering"in Chinese,and"PLGA,polylactic acid-hydroxyacetic acid copolymer,poly(lactic-co-glycolic acid)copolymer,dent*,regeneration,caries,periodontal,pulp,implant,alveolar bone"in English.Preliminary screening was conducted by reading titles and abstracts,excluding literature unrelated to the theme of the article.Based on the inclusion and exclusion criteria,a total of 119 articles were included for review.RESULTS AND CONCLUSION:In the field of stomatology,the application scope of poly(lactic-co-glycolic acid)copolymer is rapidly expanding,gradually replacing the traditional therapeutic drugs and restorative materials.Poly(lactic-co-glycolic acid)copolymer nanoparticles/microspheres can carry a variety of hydrophobic and hydrophilic active substances,demonstrating excellent delivery capabilities in caries prevention,root canal disinfection,and pulp capping treatment.In periodontal therapy,poly(lactic-co-glycolic acid)copolymer is widely used as a barrier membrane and drug carrier for periodontal tissue regeneration.Poly(lactic-co-glycolic acid)copolymer used for surface modification of implants not only enhances the antibacterial ability of the implant surface but also improves the bio-inert nature of the implant surface.The effect of pure poly(lactic-co-glycolic acid)copolymer scaffolds on treating bone defects is limited and requires the integration of 3D printing,various bioactive components,and inorganic materials to enhance scaffold performance.The combination of poly(lactic-co-glycolic acid)copolymer and stem cells can improve the effectiveness of nerve therapy,meeting clinical needs.Based on the great potential of poly(lactic-co-glycolic acid)copolymer in the field of stomatology,it is expected that in the future,repair materials with specific functions for different diseases will be produced according to different needs of oral tissue engineering.

Guided by Zhang Zhongjing's axiom that"blood stasis induces water",this study develops stage-specific treatment strategies for edema in Kidney Consumption Disorder by examining its four-stage pathogenic progression:Sluggish Flow → Stagnant Obstruction → Depressed Accumulation → Stasis Congelation.We propose an integrated approach that reinforces the root by warming the kidney and replenishing essence,while addressing the branch by activating blood circulation and promoting diuresis.Stage-specific interventions include:for the Sluggish Flow Phase,warming and tonifying kidney Yang combined with unblocking Yang to promote uri-nation;for the Stagnant Obstruction Phase,warming the kidney and replenishing essence supported by activating blood circulation and freeing the collateral channels;for the Depressed Accumulation Phase,quickening blood and resolving stasis,regulating Qi and trans-forming turbidity,along with warming the kidney and strengthening essence;and for the Stasis Congelation Phase,expelling stagnant accumulations while simultaneously regulating essence and blood.This framework advances novel pattern-determined strategies for Kid-ney Consumption edema management.