Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Fungal infection is an increasingly serious clinical problem,especially in immunocompromised patients.Fungi,such as Candida albicans,Aspergillus,and Cryptococcus,can form biofilm,which enhance their drug re-sistance and immune evasion ability,thus become major obstacles to the treatment of infection.Biofilm formation is not limited to human body,it can also form on the surface of medical devices,leading to chronic and recurrent infec-tion.This article elaborates the biofilm formation mechanisms and hazards caused by different fungi such as Candi-da albicans and Aspergillus,emphasizes immune suppression,chronic diseases,and medical devices as high-risk factors for biofilm formation.Fungi can form biofilm through multiple stages such as adhesion,proliferation,extra-cellular matrix(ECM)construction,and cell dispersion,and enhance drug resistance based on physical barriers and gene regulation.Although existing antifungal agents are effective in infection caused by planktonic fungi,their treatment efficacy on fungal biofilm is limited.Therefore,the article explores new treatment strategies,including non-pharmacological therapies such as photodynamic therapy and electric field therapy,as well as targeted gene edi-ting and the application of new biomaterials.It is necessary to strengthen the combination of basic research and clini-cal applications,develop efficient and low toxicity treatment scheme to improve the successful treatment rate for patients.

Objective:To evaluate potentially inappropriate medication (PIM) in hospitalized elderly patients with bacterial pneumonia, and explore its influencing factors.Methods:It was a single-center cross-sectional study. The study focused on elderly patients with bacterial pneumonia who were admitted to Xuanwu Hospital, Capital Medical University from January 2018 to November 2022. Patients′ gender, age, weight, length of hospital stay, diagnosis at admission, physical examination, diagnosis at discharge, comorbidities, medications, and laboratory test results were extracted from hospital information system and electronic medical records. Medication use of patients included in the analysis during their hospitalization were evaluated according to the classification of PIMs in the 5 lists of the Beer′s criteria of American Geriatrics Society. Based on whether PIM occurred, the patients were divided into with PIM group and without PIM group. The clinical features between the 2 groups were compared and the influencing factors of PIM were analyzed using multivariable logistic regression.Results:A total of 2 720 patients were included, in which 1 734 (63.75%) were male. The median age was 78 (70, 85) years and their ages ranged from 65 to 103 years. The number of drugs used per patient was 14 (10, 18) kinds, ranging from 1 to 57 kinds. The length of hospital stay was 12 (9, 17) days, ranging from 1 to 162 days. Charlson comorbidity index (CCI) was 6 (5, 8) points. Among the 2 720 patients, 1 894 (69.63%) experienced PIM, with a total of 6 166 cases of PIM. The top 3 drugs ranked by the number of PIM occurrence were antiplatelet agents (1 357 cases), benzodiazapine receptor agonists (956 cases), and antipsychotics (884 cases). The comparison of clinical characteristics between the 2 groups showed that differences in age, CCI, length of hospital stay, and number of medications between with PIM and without PIM patients were statistically significant (all P<0.001). Multivariable logistic regression results showed that CCI, length of hospital stay, and number of medications were independent influencing factors for PIM. The risk increased by 8% and 1% with one point increase in CCI and one day extension in length of hospital stay [odds ratio ( OR)=1.08, 95% confidence interval ( CI): 1.04-1.13, P<0.001; OR=1.01, 95% CI: 1.00-1.03, P=0.03]. PIM risk of patients with more than 15 concurrent medications had a 22.16 times higher PIM risk than those with less than 5 concurrent medications ( OR=22.16, 95% CI: 14.15-34.72, P<0.001). Conclusions:Hospitalized eldery patients with bacterial pneumonia who have more severe comorbidities, longer hospital stay, and multiple concomitant medications are at a higher risk of PIM occurrence. Rational medication use among these patients should be paid attention to in clinical practice.

Objective:To discuss the feasibility and safety of stage I anastomosis and T-tube fistulation in laparoscopic local resection of duodenal tumors.Methods:A descriptive case series study was used to retrospectively analyze the clinical diagnosis and treatment data of 14 patients with duodenal tumors who successfully underwent laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy in the Guangdong Provincial Hospital of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2021 to March 2024. The resection and reconstruction steps of laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube ostomy are as follows: (1) after the safe margin is clear, the duodenal tumor is completely removed in full thickness, and the specimen bag is taken out and sent to frozen section to determine the nature of the tumor and the negative margin; (2) Perforate the anterior duodenal wall below the tumor plane, place a 16# T tube, and fix it with laparoscopic purse string suture. The abdominal wall is led out through the duodenum, and the duodenal T tube fistulation is performed; (3) The duodenum was continuously sutured in a full-thickness transverse shape, and the seromuscular layer was strengthened to form a phase I anastomosis. The nutritional improvement of patients after operation was mainly observed, and the intraoperative situation and postoperative complications were recorded.Results:No conversion to laparotomy, postoperative emergency reoperation, intraoperative and postoperative complications occurred in 14 patients with duodenal tumors who completed laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy. The operation time was (225.43 ± 56.54) min, and the intraoperative blood loss was (72.14 ± 74.65) ml. The patient recovered well after operation, and no severe postoperative abdominal bleeding occurred. Postoperative gastrointestinal angiography showed that the anastomotic stoma was unobstructed, and there were no stenosis, anastomotic leakage and other related complications. There was no significant difference in serum albumin [(37.09 ± 3.53) g/L vs. (37.52 ± 4) g/L] and hemoglobin [(100.79 ± 31.93) g/L vs. (103.07 ± 19.6) g/L] between before and 1 week after operation ( P > 0.05). Conclusion:Laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube fistulation can be used as one of the safe and feasible improved methods for local resection of duodenal tumor to effectively reduce the occurrence of related complications.

Objective:To study the efficiency and biosafety of Electrochemical advanced oxidation processes(EAOP)in dental bleaching,and conduct preliminary application.Methods:Indigo carmine and coffee were used as the indicator to assess the effi-cacy of EAOP.High resistance meter was used to measure the resistance of the tooth to verify the safety of the working voltage.Twenty wisdom teeth after tooth extraction were collected,dyed and bleached in vitro to verify the bleaching efficiency.Subsequent-ly,the bleached teeth were examined by scanning electron microscopy,hardness testing,and bacterial adhesion experiments to as-sess surface damage.To determine its cytotoxicity,cells were co-cultured with electrolyte.Initial samples of bleaching tray was prepared,and its durability were verified.Results:The EAOP could bleach indigo carmine within 10 min and coffee within 90 min at an operating voltage of 8 V.The resistance at the groove of the tooth socket was(3.4±1.2)MΩ,and the theoretical calculated current was less than 3 μA.The efficiency of EAOP tooth bleaching was slightly lower than that of traditional office bleaching and higher than that of home bleaching.Compared with the traditional bleaching method,scanning electron microscopy showed that EAOP had less demineralization effect on tooth surface.The tooth hardness before and after bleaching had no statistical difference(P=0.912).The bacterial adhesion test after tooth bleaching showed that EAOP method could reduce about 60％bacterial adhe-sion(P＜0.001).The cytotoxicity test showed that EAOP electrolyte had no obvious toxic effect.The durability test shows that the bleached denture still has good bleaching effect after 20 h of use.Conclusion:Compared with the traditional bleaching method,EAOP bleaching had excellent tooth bleaching effect,little effect on tooth damage,high safety,and the related bleaching devices had good durability.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Fungal infection is an increasingly serious clinical problem,especially in immunocompromised patients.Fungi,such as Candida albicans,Aspergillus,and Cryptococcus,can form biofilm,which enhance their drug re-sistance and immune evasion ability,thus become major obstacles to the treatment of infection.Biofilm formation is not limited to human body,it can also form on the surface of medical devices,leading to chronic and recurrent infec-tion.This article elaborates the biofilm formation mechanisms and hazards caused by different fungi such as Candi-da albicans and Aspergillus,emphasizes immune suppression,chronic diseases,and medical devices as high-risk factors for biofilm formation.Fungi can form biofilm through multiple stages such as adhesion,proliferation,extra-cellular matrix(ECM)construction,and cell dispersion,and enhance drug resistance based on physical barriers and gene regulation.Although existing antifungal agents are effective in infection caused by planktonic fungi,their treatment efficacy on fungal biofilm is limited.Therefore,the article explores new treatment strategies,including non-pharmacological therapies such as photodynamic therapy and electric field therapy,as well as targeted gene edi-ting and the application of new biomaterials.It is necessary to strengthen the combination of basic research and clini-cal applications,develop efficient and low toxicity treatment scheme to improve the successful treatment rate for patients.

Objective To evaluate the effectiveness,safety and economy of generic venlafaxine sustained-release capsules and the original drug in clinical practice based on real world clinical data.Methods This is a multicenter,retrospective real-world study.The information of outpatients who used venlafaxine sustained-release capsules in 7 hospitals from October 2021 to October 2022 was collected,including prescription data and laboratory data.They were divided into generic drug group and original drug group.After the baseline level was corrected by propensity score match method,the prescription daily dose,plasma concentration,medication possession ratio,the continuous medication rate for 3,6 and 9 months,dressing change rate,the incidence of adverse reactions,the frequency of drug use,the average daily cost,the annual cost per capita and the proportion of the average annual cost of drugs were compared between the two groups.Results After the baseline level was corrected by propensity score matching method,the prescription daily dose and medication possession ratio(MPR≥0.8)in the generic drug group were higher than that of the original drug group(P＜0.05).There was no statistically difference in plasma concentration between the two groups(P=0.294).The continuous medication rate for 3,6 and 9 months in the generic drug group were statistically higher than those in the original drug group(P＜0.01).The single dressing change rate of the generic drug group was lower than that of the original drug group(P=0.032).There was no significant difference in the rate of secondary dressing change between the two groups(P=1.000).There were no significant differences in the incidence of abnormal ALT,AST,TC,Na,APTT,and PLC between two groups(P＞0.05).The average daily cost of the generic drug group was lower than that of the original drug group.The per capita annual cost of drugs and the proportion of average annual cost of drugs in the generic drug group were significantly lower than those in the original drug group(P＜0.01).Conclusion In the actual clinical diagnosis and treatment,no clinically significant differences in effectiveness and safety were found between the generic venlafaxine sustained-release capsule and the original-patented,while the economic advantages of the generic drug were better than that of the original-patented drug.

Objective:To discuss the feasibility and safety of stage I anastomosis and T-tube fistulation in laparoscopic local resection of duodenal tumors.Methods:A descriptive case series study was used to retrospectively analyze the clinical diagnosis and treatment data of 14 patients with duodenal tumors who successfully underwent laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy in the Guangdong Provincial Hospital of Chinese Medicine and the First Affiliated Hospital of Guangzhou University of Chinese Medicine from October 2021 to March 2024. The resection and reconstruction steps of laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube ostomy are as follows: (1) after the safe margin is clear, the duodenal tumor is completely removed in full thickness, and the specimen bag is taken out and sent to frozen section to determine the nature of the tumor and the negative margin; (2) Perforate the anterior duodenal wall below the tumor plane, place a 16# T tube, and fix it with laparoscopic purse string suture. The abdominal wall is led out through the duodenum, and the duodenal T tube fistulation is performed; (3) The duodenum was continuously sutured in a full-thickness transverse shape, and the seromuscular layer was strengthened to form a phase I anastomosis. The nutritional improvement of patients after operation was mainly observed, and the intraoperative situation and postoperative complications were recorded.Results:No conversion to laparotomy, postoperative emergency reoperation, intraoperative and postoperative complications occurred in 14 patients with duodenal tumors who completed laparoscopic local resection of duodenal tumors + phase I anastomosis + T-tube ostomy. The operation time was (225.43 ± 56.54) min, and the intraoperative blood loss was (72.14 ± 74.65) ml. The patient recovered well after operation, and no severe postoperative abdominal bleeding occurred. Postoperative gastrointestinal angiography showed that the anastomotic stoma was unobstructed, and there were no stenosis, anastomotic leakage and other related complications. There was no significant difference in serum albumin [(37.09 ± 3.53) g/L vs. (37.52 ± 4) g/L] and hemoglobin [(100.79 ± 31.93) g/L vs. (103.07 ± 19.6) g/L] between before and 1 week after operation ( P > 0.05). Conclusion:Laparoscopic local resection of duodenal tumor + phase I anastomosis + T-tube fistulation can be used as one of the safe and feasible improved methods for local resection of duodenal tumor to effectively reduce the occurrence of related complications.