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.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.

Objective:To investigate the demand of rural elderly in Shenyang for integrated medical and elderly care service model,providing references for the improvement and development of rural integrated medical and elderly care services in Shenyang.Methods:Elderly individuals from selected rural areas in Shenyang were randomly sampled as study subjects.A questionnaire survey was conducted to analyze their basic demographics,satisfaction with current elderly care services,and demand levels for integrated medical and elderly care programs.Multiple linear regression analysis was used to identify factors influencing the demand for integrated medical and elderly care services among rural elderly.Results:The satisfaction scores of the rural elderly for medical care,cultural and recreational activities,spiritual comfort,and daily living assistance were 3.86±1.37,3.67±1.36,3.49±1.45,and 3.15±1.58,respectively.Multiple linear regression analysis showed that gender,monthly family income,occupation,insurance situation,living situation,and self-care ability were factors influencing the demand for integrated medical and elderly care services(P＜0.05).Conclusion:The demand for integrated medical and elderly care service model among rural elderly is affected by multiple factors.

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.

Objective:To investigate the demand of rural elderly in Shenyang for integrated medical and elderly care service model,providing references for the improvement and development of rural integrated medical and elderly care services in Shenyang.Methods:Elderly individuals from selected rural areas in Shenyang were randomly sampled as study subjects.A questionnaire survey was conducted to analyze their basic demographics,satisfaction with current elderly care services,and demand levels for integrated medical and elderly care programs.Multiple linear regression analysis was used to identify factors influencing the demand for integrated medical and elderly care services among rural elderly.Results:The satisfaction scores of the rural elderly for medical care,cultural and recreational activities,spiritual comfort,and daily living assistance were 3.86±1.37,3.67±1.36,3.49±1.45,and 3.15±1.58,respectively.Multiple linear regression analysis showed that gender,monthly family income,occupation,insurance situation,living situation,and self-care ability were factors influencing the demand for integrated medical and elderly care services(P＜0.05).Conclusion:The demand for integrated medical and elderly care service model among rural elderly is affected by multiple factors.

OBJECTIVE To conduct a literature review of one case of follicular lymphoma complicated with iliac bone Cryptococcus neoformans infection so as to raise the understanding of such pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.METHODS The clinical data were collected from one case of follicular lymphoma patient complicated with C.neoformans infection who was treated in Xinrui Hospital of Xin-wu District,Wuxi City on Feb.24,2023 and retrospectively analyzed.All of relevant literatures regarding to the subject were retrieved in Pubmed,CNKI,Wanfang and VIP databases,and the clinical data of the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma with C.neoformans infection were screened out and summa-rized.RESULTS The case was a 28-year-old male and had the underlying disease of follicular lymphoma.The C.neoformans was detected by iliac bone histopathology and metagenome next generation sequencing(mNGS).The condition of the patient improved after the treatment with amphotericin B cholesterol sulphate com-pound and fluconazole.A total of 28 patients,with this case included,were involved in the literature review,23 of whom were male,and 5 were female,and the age ranged between 16 and 79 years old.With respect to major in-fection sites,there were 15(53.57％)cases of cerebral infection,9(32.14％)cases of blood infections,7(25.00％)cases of pulmonary infection,4(14.285％)cases of skin infections,2(7.14％)cases of muscle tis-sue infections,2(7.14％)cases of pleural effusion infections,2(7.14％)cases of bone infections and 1(3.57％)case of bone marrow infection.Totally 11 patients had disseminated Cryptococcus infection,accounting for 39.28％.CONCLUSIONS The C.neoformans infection is seldom detected in the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma.The brain is the major infection site with the high probability of dissemina-ted infection.It is necessary for the hospital to deepen the understanding of the pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.

OBJECTIVE To conduct a literature review of one case of follicular lymphoma complicated with iliac bone Cryptococcus neoformans infection so as to raise the understanding of such pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.METHODS The clinical data were collected from one case of follicular lymphoma patient complicated with C.neoformans infection who was treated in Xinrui Hospital of Xin-wu District,Wuxi City on Feb.24,2023 and retrospectively analyzed.All of relevant literatures regarding to the subject were retrieved in Pubmed,CNKI,Wanfang and VIP databases,and the clinical data of the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma with C.neoformans infection were screened out and summa-rized.RESULTS The case was a 28-year-old male and had the underlying disease of follicular lymphoma.The C.neoformans was detected by iliac bone histopathology and metagenome next generation sequencing(mNGS).The condition of the patient improved after the treatment with amphotericin B cholesterol sulphate com-pound and fluconazole.A total of 28 patients,with this case included,were involved in the literature review,23 of whom were male,and 5 were female,and the age ranged between 16 and 79 years old.With respect to major in-fection sites,there were 15(53.57％)cases of cerebral infection,9(32.14％)cases of blood infections,7(25.00％)cases of pulmonary infection,4(14.285％)cases of skin infections,2(7.14％)cases of muscle tis-sue infections,2(7.14％)cases of pleural effusion infections,2(7.14％)cases of bone infections and 1(3.57％)case of bone marrow infection.Totally 11 patients had disseminated Cryptococcus infection,accounting for 39.28％.CONCLUSIONS The C.neoformans infection is seldom detected in the patients with HIV-negative Hodgkin's/non-Hodgkin's lymphoma.The brain is the major infection site with the high probability of dissemina-ted infection.It is necessary for the hospital to deepen the understanding of the pathogen in the field of HIV-negative Hodgkin's/non-Hodgkin's lymphoma.

Objective:To investigate the short-term efficacy of left-sided three-port total laparoscopic distal gastrectomy (TPTLDG).Methods:The prospective randomized controlled study was conducted. The 68 patients undergoing laparoscopic distal gastrectomy in the First Affiliated Hospital of Air Force Medical University from March 2022 to March 2023 were collected. All patients were randomly assigned to the TPTLDG group with a double number, and to the five-port laparoscopic distal gastrectomy (FPLDG) group with a single number, respectively. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of perioperative condition; (3) comparison of complications during postoperative 30 days; (4) comparison of pathological examination. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or continuous correction chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 59 patients of gastric cancer were selected for eligibility. There were 40 males and 19 females, aged 59.00(52.00, 67.00)years. The gender (male, female), age, body mass index (BMI), Caprini score (≤2, ≥3), nutritional risk screening 2002 (<3, ≥3), Eastern Coopera-tive Oncology Group performance status (0, 1), preoperative hypersensitive C-reactive protein, preoperative IL-6, preoperative white blood cell count, preoperative albumin were 19, 11, 59.00(51.25,65.25)years, 21.92(20.93,22.73)kg/m 2, 7, 23, 24, 6, 18, 12, 0.78(0.78,1.46)mg/L, 3.07(1.50,10.56)μg/L, 6.07(4.94,7.19)×10 9/L, 44.30(40.83, 46.15) g/L in the 30 patients of TPTLDG group, versus 21, 8, 57.00(51.00, 67.00)years, 21.90(20.95, 23.35)kg/m 2, 11, 18, 24, 5, 17, 12, 1.13(0.78,11.40)mg/L, 5.56(1.88,15.12)μg/L, 5.54(4.71,6.70)×10 9/L, 43.55(40.25,44.88)g/L in the 29 patients of FPLDG group, showing no significant difference in the above indicators between the two groups ( χ2=0.557, Z=-0.444, -0.805, χ2=1.482, 0.074, 0.012, Z=-1.259, -1.262, -0.819, -1.199, P>0.05), confounding bias ensured comparability between the two groups. (2) Comparison of perioperative condition. The length of incision, time to removing drainage tube, IL-6 at postoperative day 3, cost of hospital stay were 6.65(6.48,6.93)cm, 3.00(0,3.00)days, 29.18 (13.67, 43.53)μg/L, 84 164.15(73 084.72, 96 782.14)yuan in the TPTLDG group, versus 8.00(7.50,8.35)cm, 3.00(3.00,4.00)days, 47.56(21.31,85.79)μg/L, 92 120.43(87 069.33, 113 089.74)yuan in the FPLDG group, showing significant differences in the above indicators between the two groups ( Z=-11.065, -2.141, -2.940, -2.220, P<0.05). (3) Comparison of complications during postoperative 30 days. The incidence rate of complications during postoperative 30 days was 30.00%(9/30) and 24.14%(7/29) in the TPTLDG group and FPLDG group, respectively, showing no significant difference between the two groups ( χ2=0.256, P>0.05). (4) Comparison of pathological examination. Cases with pathological N staging as 0 stage, 1 stage, 2 stage, 3 stage were 22, 2, 4, 2 in the TPTLDG group, versus 13, 7, 4, 5 in the FPLDG group, showing a significant difference between the two groups ( Z=-2.021, P<0.05). Conclusion:TPTLDG is safe and feasible for gastric cancer, with a good short-term efficacy.

Objective:To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSCs) transfected with recombinant rat platelet-derived growth factor BB (rrPDGF-BB) gene on the distraction osteogenesis.Methods:From October, 2019 to June, 2020, 48 batches of BMSCs were cultured from 48 young SD rats, 24 of which were transfected with rrPDGF-BB gene by lentivirus. Meanwhile, other 72 male adult SD rats were randomly selected to establish the right femoral distraction osteogenesis model. The rats were equally divided into 3 groups. PBS, BMSCs without intervention and BMSCs transfected with rrPDGF-BB gene were injected into the distraction space of each group of rats assigned as Blank group, Negative group and Experimental group, respectively. Results of the experiment were evaluated by means of imaging and immunohistochemistry. P<0.05 indicated a statistically significant difference. Results:The cultured BMSCs grew well. The expression of CD34(0.1%) and CD45(2.8%) in the third generation of BMSCs was low, and that of CD29 (95.1%) was high, which was consistent with the phenotype of BMSCs described in literatures. After transfection, the expression of green fluorescence gradually increased with the extension of transfection time, confirming the success of transfection. After 14 days, all rats reached the expected distance of distraction. The rats were observed at assigned time points in 2, 4 and 8 weeks. The photos of femur specimen showed that continuous callus could be seen in the experimental group, the hardness and colour were close to the normal bone tissue, and the activity of the distraction space was poor, which was lower than that of the blank group. X-ray examination showed that there were more new callus in the experimental group, and the bone marrow cavity was re-canalized earlier than that of the blank group; Micro-CT examination, in sagittal plane, showed that the distraction space of the experimental group healed well, the broken end was connected, and the recanalization of bone marrow cavity was earlier than that of the blank group; Micro-CT parameters of each group showed that trabecular thickness[(0.297±0.005) mm], trabecular number [(1.663±0.032) mm], bone volume fraction[(59.832±2.187)%] and bone mineral density[(0.586±0.014) g/cm 3] of the experimental group were the greatest, while trabecular separation[(0.399±0.051) mm] of the experimental group was the smallest. There was statistical difference between each group( P < 0.05); HE staining and VEGF immunohistochemistry showed that the vessels and chondrocytes formed earlier and were more in the experimental group than that in the blank group. In 8 weeks, the new callus joined into one piece under the microscope in the experimental group, and the bone marrow cavity was re-canalized with a large number of red blood cells. Conclusion:Studies have shown that BMSCs transfected with rrPDGF-BB gene can promote the formation of callus in the distraction area of rats, shorten the mineralisation time of new callus, and promote the maturation of new bone in the area of distraction osteogenesis.