A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

The complex anatomical structure and physiological barriers of the eye present substantial challenges for local drug delivery, leading to suboptimal ocular drug bioavailability, which typically remains below 5% in conventional ophthalmic formulations. Frequent or high-dose administration not only increases the treatment burden but also heightens the risk of both local and systemic adverse effects. Liposomes, as an advanced drug delivery system, enhance ocular bioavailability through their biocompatibility and targeted delivery properties. Recent innovations in surface modification and functionalization have further enhanced their ability to overcome ocular barriers and facilitate controlled drug release. Liposome-based formulations have demonstrated significant therapeutic potential for diseases such as glaucoma and dry eye syndrome. Drawing on the research advancements over the past 5 a, this article systematically reviews the innovative design strategies and applications of liposomes in ocular drug delivery, with the aim of providing theoretical basis and technical reference for the development of new ophthalmic drugs.

OBJECTIVE: To compare clinical efficacy of tibial transverse transport (TTT) microcirculation reconstruction and periosteal distraction in treating patients with early diabetic foot(DF). METHODS: From June 2021 to June 2024, 60 patients with DF were admitted and divided into bone transport group and stretch group according to different treatment methods. There were 30 patients in bone transport group, including 16 males and 14 females;aged from 48 to 65 years old with an average of (55.59±3.78) years old;the course of disease ranged from 2 to 9 months with an average of(5.95±1.32) months;TTT microcirculation reconstruction surgery was performed. There were 30 patients in distraction group, including 17 males and 13 females;aged from 47 to 67 years old with an average of (55.24±3.81) years old;the course of disease ranged from 2 to 10 months with an average of (5.68±1.54) months;periosteal distraction surgery was performed. The skin temperature of the affected feet, the time of getting out of bed and walking after operation, the time of full weight-bearing, the wound healing time and complications were compared between two groups;the pain was evaluated by visual analogue scale (VAS) before operation and one month after operation respectively;the changes of blood flow velocity of dorsal foot arteries, ankle brachial index(ABI), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) before and after operation at 3 months were compared between two groups. RESULTS: All patients were followed up for 3 to 4 months with an average of (3.52±0.12) months. There were no statistically significant differences in comparison of foot skin temperature, postoperative walking time, full weight-bearing time and complications between two groups (P>0.05). The wound healing time of bone transport group (61.26±7.31) days was shorter than that of distraction group (70.17±7.15) days, and the difference was statistically significant (P<0.05). Postoperative VAS at 1 month of bone transport group (2.19±0.21) was lower than that of distraction group (2.55±0.20), and the difference was statistically significant (P<0.05). At 3 months after operation, the blood flow velocity of dorsal foot artery, ankle-brachial index, EGF and bFGF in bone transport group were(34.73±4.18) cm·s^-1, (0.95±0.13), (716.61±71.13) pg·ml^-1 and (175.69±31.28) pg·ml^-1, respectively;which were higher than that of distraction group (31.86±3.23) cm·s^-1, (0.84±0.11), (677.37±70.21) pg·ml^-1, (149.26±30.13) pg·ml^-1, and the differences were statistically significant (P<0.05). There was no recurrence of ulcers in situ or at other sites in both groups during follow-up. CONCLUSION Compared with periosteal distraction, TTT microcirculation reconstruction surgery has a definite effect in the treatment of early DF. It could effectively reduce pain level, improve blood flow indicators and vascular endothelial function of the foot, and has a relatively high safety.
Humans ; Male ; Female ; Middle Aged ; Aged ; Tibia/blood supply* ; Diabetic Foot/physiopathology* ; Microcirculation ; Periosteum/surgery* ; Plastic Surgery Procedures/methods* ; Osteogenesis, Distraction

OBJECTIVES: Oblique lateral interbody fusion (OLIF) has become a well-established treatment for lumbar spinal stenosis (LSS) due to its advantages of being minimally invasive, effective, and associated with fewer complications. However, relying solely on lateral fixation provides limited strength and uneven load distribution. Conventional posterior bilateral fixation after OLIF typically requires intraoperative repositioning, increases fluoroscopy frequency, and involves extensive dissection of posterior muscles and soft tissues, resulting in greater trauma, blood loss, and risks of dural tear, nerve root injury, and persistent postoperative low back pain. This study aims to compare the clinical efficacy of robot-assisted single-position OLIF with lateral plating and posterior unilateral fixation, OLIF with lateral fixation alone, and OLIF combined with posterior bilateral fixation for treating single-segment LSS, and to explore how to enhance fixation stability, reduce trauma, and achieve precise minimally invasive outcomes without changing patient positioning. METHODS: A retrospective analysis was conducted on the clinical data from patients treated for single-segment LSS between January 2020 and June 2023 at the First Affiliated Hospital of Kunming Medical University. Patients were divided into 3 groups: Robot group (robot-assisted single-position OLIF with lateral plate and posterior unilateral fixation, 33 cases), lateral group (OLIF with lateral fixation alone, 52 cases), and combined group (OLIF with posterior bilateral fixation, 45 cases). Surgical time, intraoperative blood loss, fluoroscopy frequency, hospital stay, pedicle screw placement accuracy, and complication rates were recorded. Pain visual analogue scale (VAS) scores and Oswestry disability index (ODI) scores were assessed preoperatively, postoperatively, and at the final follow-up. Radiological evaluations (X-ray, computed tomography, and magnetic resonance imaging) measured interbody disc height (IDH), intervertebral foraminal height (IFH), and cross-sectional area (CSA) of the dural sac. Differences between pre- and postoperative imaging indices were statistically analyzed, and complication rates, fusion rates, and cage subsidence rates were recorded. RESULTS: All patients exhibited good positioning of internal fixation devices and cages, with significant symptom relief and no cases of spinal cord injury or symptom worsening. The follow-up time was (15.2±3.6) months. The operation time of the robot group was (70.62±8.99) min, which was longer than that of the lateral group (45.90±6.09) min and shorter than that of the combined group (110.12±8.44) min. The intraoperative blood loss of the robot group was (44.27±6.87) mL, which was more than that of the lateral group (33.58±9.73) mL and less than that of the combined group (79.19±10.35) mL. The number of intraoperative fluoroscopy times of the robot group was (9.49±2.25), which was comparable to that of the lateral group (7.45±2.02) but less than that of the combined group (12.24±4.25). The hospital stay of the robot group was (9.28±2.10) days, which was longer than that of the lateral group (7.95±1.91) days and shorter than that of the combined group (12.49±5.07) days. The screw placement accuracy of the robot group was 98.48%, which was higher than that of the combined group (90.55%). Postoperative and final follow-up VAS and ODI scores were significantly lower than preoperative scores in all 3 groups (all P<0.05), and there were no significant differences in preoperative VAS and ODI scores among the groups (all P>0.05). Radiologically, IDH, IFH, and CSA at the surgical segment were significantly increased postoperatively and at final follow-up compared to preoperatively and at final follow-up compared to preoperative values (all P<0.05), with no significant differences among the groups postoperatively (all P>0.05). Internal fixation remained stable during the follow-up period, and all cages achieved fusion at final follow-up. The intervertebral fusion rate of the robot-assisted group was 93.40%, which was similar to that of the combined group (95.56%) and higher than that of the lateral approach group (90.34%). The complication rate of the robot-assisted group was 6.1%, which was comparable to that of the combined group (8.9%) and lower than that of the lateral approach group (15.4%) (P<0.05). No cases of fixation loosening or breakage were observed throughout the follow-up period. CONCLUSIONS Robot-assisted single-position OLIF with lateral plate combined with posterior unilateral fixation effectively achieves indirect decompression and excellent spinal stability without the need for intraoperative repositioning. It provides high pedicle screw accuracy, reduces intraoperative blood loss, fluoroscopy times, and complication rates, offering a fully minimally invasive new treatment option for single-segment LSS.
Humans ; Spinal Stenosis/surgery* ; Robotic Surgical Procedures/methods* ; Lumbar Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Treatment Outcome ; Bone Plates ; Minimally Invasive Surgical Procedures/methods* ; Adult

Nanotechnologies seek to overcome inherent deficiencies of conventional diagnosis and treatment, which attracted sustained attention and a limited number of nanomedicines approved by the FDA. However, the critical gaps in clinical translation remain, and nanomedicines that were initially heralded as magic bullets have yet to reach their realistic potential. The major obstacles of fabrication technologies may be overlooked in the nanoparticles' journey. Suboptimal manufacturing strategies partly hampered the inefficient transformation. In this review, we discuss the nanoparticle manufacturing strategies of "Top-Down" and "Bottom-Up" on precise nanoscale fabrication, including artificial intelligence introduced to guided nanomedicine fabrication for accelerating the transformation. Re-engineering existing nanomedicine fabrication, individual manufacturing, and modular technology might highlight the dilemmas of nanomedicines to meet their initial expectations.

OBJECTIVES: To investigate the synergistic mechanism of the traditional Chinese medicine Rosa laevigata Michx. (RLM) for treatment of pulmonary arterial hypertension (PAH). METHODS: Network pharmacological analysis was carried out to screen the active ingredients of RLM and PAH disease targets and construct the "component-target-disease" interaction network, followed by gene enrichment analysis and molecular docking studies. In the cell experiments, primary cultures of rat pulmonary arterial smooth muscle cells were exposed to hypoxia for 24 h and treated with solvent or 100, 200 and 300 mg/mL RLM, and the changes in cell proliferation were detected using Western blotting for PCNA and immunofluorescence staining. In the animal experiment, male SD rats were randomized into 5 control group, monocrotaline (MCT) solvent group, and MCT with RLM (100, 200 and 300 mg/mL) treatment groups. HE staining and immunofluorescence staining were used to observe histopathological changes in the pulmonary blood vessels of the rats. RESULTS: Seven core active ingredients (including β-sitosterol and kaempferol) in RLM and 39 key disease targets were identified, and molecular docking showed that SRC was a high-affinity target. KEGG enrichment analysis showed that the differential genes were significantly enriched in calcium signaling and PI3K-AKT pathways. In rat pulmonary arterial smooth muscle cells, hypoxic exposure significantly up-regulated cellular expression of PCNA and phosphorylation levels of Src and AKT1, which were obviously lowered by RLM treatment. In RLM-treated rat models, the mean pulmonary artery pressure and right ventricular hypertrophy index (Fulton index) were significantly reduced, the tricuspid annular plane systolic excursion (TAPSE) was improved, and pulmonary vascular wall thickening and fibrosis were obviously ameliorated. CONCLUSIONS RLM inhibits pulmonary arterial smooth muscle cell proliferation in rat models of hypertension possibly by regulating the Src-AKT1 axis, suggesting the potential of RLM as a new natural drug for treatment of pulmonary hypertension.
Animals ; Cell Proliferation/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Pulmonary Artery/cytology* ; Male ; Rats ; Myocytes, Smooth Muscle/cytology* ; Hypertension, Pulmonary/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Muscle, Smooth, Vascular/cytology* ; src-Family Kinases/metabolism* ; Cells, Cultured

OBJECTIVE: To investigate the impact of autophagy on cardiac tissue injury following common bile duct ligation (CBDL) in rats. METHODS: Twenty-four SPF grade healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, with 6 rats in each group. The sham-operated (Sham) group underwent only dissection of the common bile duct without ligation. The CBDL group underwent CBDL to simulate jaundice-induced myocardial injury. The autophagy inhibitor 3-methyladenine (3-MA)+CBDL group was intraperitoneally injected with 15 mg/kg 3-MA 2 hours before modeling, and then injected once every other day. The CBDL+autophagy enhancer rapamycin (Rapa) group was intraperitoneally injected with Rapa 1 mg/kg 0.5 hour after modeling, and then injected once every other day. The rats in each group were sacrificed 2 weeks after surgery, and blood was taken from the inferior vena cava. Serum total bilirubin (TBil), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) were detected by using a fully automated animal biochemical analyzer. Serum oxidative stress marker superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric assay. The heart tissues of rats were taken and pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining. Transmission electron microscope was used to observe autophagosomes after double staining with uranyl acetate and lead citrate. The expressions of autophagy-related proteins were detected using Western blotting. RESULTS: Compared with the Sham group, the serum SOD activity of rats in the CBDL group was significantly decreased, while the serum MDA, TBil, ALT, AST, LDH, and CK-MB were significantly increased; the expressions of autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) were significantly increased, and p62 protein expression was significantly decreased. Autophagosomes were seen under electron microscopy in the CBDL group, and cardiac histopathological morphology showed focal necrosis in the myocardium as well as infiltration of inflammatory cells, dilatation of small interstitial blood vessels, and myocardial fiber degeneration. Compared with the CBDL group, cardiac tissue injury in rats was attenuated by pretreatment with the autophagy inhibitor 3-MA, with a decrease in inflammatory cell infiltration in myocardial tissue, a reduction in interstitial vasodilatation, and a decrease in the area of myocardial fibrosis; a decrease in the number of autophagosomes by electron microscopy; and a further rise in the viability of serum TBil, ALT, and AST [TBil (μmol/L): 184.40±6.74 vs. 120.70±16.93, ALT (U/L): 501.10±62.18 vs. 178.80±22.30, AST (U/L): 806.50±76.92 vs. 275.50±55.81, all P < 0.01], as well as a decrease in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 85.00±5.29 vs. 107.50±7.86, MDA (μmol/L): 10.72±0.93 vs. 15.06±1.88, LDH (U/L): 387.40±119.50 vs. 831.30±84.35, CK-MB (U/L): 320.10±14.04 vs. 814.70±75.66, all P < 0.05]. The expressions of the autophagy-related proteins Beclin-1 and LC3-II/I in cardiac tissues were significantly decreased [Beclin-1 protein (Beclin-1/GAPDH): 0.67±0.04 vs. 0.89±0.01, LC3-II/I ratio: 0.93±0.03 vs. 1.09±0.01, both P < 0.01], and p62 protein expression was significantly increased (p62/GAPDH: 0.99±0.01 vs. 0.60±0.01, P < 0.01). In contrast, compared with the CBDL group, after administration of the autophagy enhancer Rapa, the rats showed increased cardiac tissue injury, increased inflammatory cell infiltration in myocardial tissues, increased interstitial vasodilatation, and increased area of myocardial fibrosis; an increase in autophagosomes was seen by electron microscopy; the change tendency of serum biochemical indicators and proteins in myocardial tissues were opposite with autophagy inhibition group with a decrease in serum TBil, ALT, and AST [TBil (μmol/L): 22.00±3.21 vs. 120.70±16.93, ALT (U/L): 72.13±5.97 vs. 178.80±22.30, AST (U/L): 135.20±12.95 vs. 275.50±55.81, all P < 0.05], as well as a increase in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 208.00±2.65 vs. 107.50±7.86, MDA (μmol/L): 20.38±0.40 vs. 15.06±1.88, LDH (U/L): 1 268.00±210.90 vs. 831.30±84.35, CK-MB (U/L): 1 150.00±158.70 vs. 814.70±75.66, all P < 0.05]. The protein expressions of Beclin-1 and LC3-II/I in cardiac tissues were significantly increased [Beclin-1 protein (Beclin-1/GAPDH): 0.96±0.01 vs. 0.89±0.01, LC3-II/I ratio: 1.19±0.01 vs. 1.09±0.01, both P < 0.05], and p62 protein expression was significantly decreased (p62/GAPDH: 0.19±0.02 vs. 0.60±0.01, P < 0.01). CONCLUSIONS Activation of autophagy in CBDL rats led to myocardial tissue injury and reduced cardiac function. Inhibition of autophagy improved cardiac tissue injury in CBDL rats, while increasing autophagy exacerbated myocardial tissue injury.
Animals ; Autophagy ; Rats, Sprague-Dawley ; Male ; Ligation ; Rats ; Common Bile Duct/surgery* ; Myocardium/pathology* ; Adenine/pharmacology*

Objective:To investigate the clinical effect of autologous fat transplantation combined with hair transplantation in the treatment of hard and/or thin scalp flat scar after burn.Methods:The clinical data of patients with hard and thin scalp scar after burn admitted to the Department of Plastic Surgery of Peking University Third Hospital from January 2017 to December 2022 were retrospectively analyzed. Fat was extracted from the lower abdomen or outer thigh during the operation, and then injected into the scalp scar after standing for 15 minutes, about 0.8 ml/cm 2 under the hard and/or thin scar area, and 0.2-0.4 ml/cm 2 under the thick and soft scar area. Three months after fat transplantation, hair transplantation was performed in the scar bald area, and the transplant density was 25-35 follicular units (FUs)/cm 2 in the hard and thin scar area, and 30-40 FUs /cm 2 in the thick and soft scar area. The Vancouver scar scale (VSS) was used by two third party plastic surgeons to score the hard and/or thin scar areas of the scalp before and 3 months after scalp fat transplantation. The VSS score was expressed as M ( Q1, Q3), and the preoperative and postoperative data were compared by paired sample Wilcoxon signed rank test. During hair transplantation, the density of implanted hair in the hard and/or thin scar area were recorded. The density of living hair at these sites was measured at the last follow-up, and then the survival rate of hair (living hair density/implant hair density ×100%) was calculated. A third party plastic surgeon evaluated the extent to which scalp scars in the hair transplant area were covered, including completely covered, basically covered, partially covered. Patients’ evaluation with the surgical result was divided into very satisfied, satisfied and dissatisfied. Results:A total of 57 patients with scalp scar after burn were included in this group, including 31 males and 26 females, aged 13-47 years old. The time from scalp scarring to treatment was 8-41 years. The area of scalp scar was 17-120 cm 2, with an average of 63.3 cm 2. The fat injection volume of 57 patients was 13-75 ml. The hair transplantation was performed 3-8 months after a single fat filling procedure. The total amount of hair transplantation was 510-3 120 FUs. The total score of postoperative scar VSS was 4(3, 4), significantly lower than the preoperative score of 7(6, 7) ( W=6.70, P < 0.001). The color, thickness, blood vessel distribution and softness were significantly reduced compared with those before surgery ( P< 0.01). All patients were followed up for 12-18 months (mean, 14 months) after hair transplantation. The survival rate of hair in hard and thin scar area was 68.2% (22.7 FUs/cm 2/33.3 FUs/cm 2) to 89.7% (26.1 FUs/cm 2/29.1 FUs/cm 2), with an average of 81.3%. In 32 patients, scalp scars were completely covered. The scalp scar of 25 patients was basically covered. Twenty-nine patients were very satisfied with the result of the operation, and 28 patients were satisfied. Conclusion:The high survival rate of hair transplantation can be obtained by injecting fat under the hard and/or thin scalp scars before hair transplantation, which is an effective method to repair scalp scars.

Objective:To investigate the clinical effect of autologous fat transplantation combined with hair transplantation in the treatment of hard and/or thin scalp flat scar after burn.Methods:The clinical data of patients with hard and thin scalp scar after burn admitted to the Department of Plastic Surgery of Peking University Third Hospital from January 2017 to December 2022 were retrospectively analyzed. Fat was extracted from the lower abdomen or outer thigh during the operation, and then injected into the scalp scar after standing for 15 minutes, about 0.8 ml/cm 2 under the hard and/or thin scar area, and 0.2-0.4 ml/cm 2 under the thick and soft scar area. Three months after fat transplantation, hair transplantation was performed in the scar bald area, and the transplant density was 25-35 follicular units (FUs)/cm 2 in the hard and thin scar area, and 30-40 FUs /cm 2 in the thick and soft scar area. The Vancouver scar scale (VSS) was used by two third party plastic surgeons to score the hard and/or thin scar areas of the scalp before and 3 months after scalp fat transplantation. The VSS score was expressed as M ( Q1, Q3), and the preoperative and postoperative data were compared by paired sample Wilcoxon signed rank test. During hair transplantation, the density of implanted hair in the hard and/or thin scar area were recorded. The density of living hair at these sites was measured at the last follow-up, and then the survival rate of hair (living hair density/implant hair density ×100%) was calculated. A third party plastic surgeon evaluated the extent to which scalp scars in the hair transplant area were covered, including completely covered, basically covered, partially covered. Patients’ evaluation with the surgical result was divided into very satisfied, satisfied and dissatisfied. Results:A total of 57 patients with scalp scar after burn were included in this group, including 31 males and 26 females, aged 13-47 years old. The time from scalp scarring to treatment was 8-41 years. The area of scalp scar was 17-120 cm 2, with an average of 63.3 cm 2. The fat injection volume of 57 patients was 13-75 ml. The hair transplantation was performed 3-8 months after a single fat filling procedure. The total amount of hair transplantation was 510-3 120 FUs. The total score of postoperative scar VSS was 4(3, 4), significantly lower than the preoperative score of 7(6, 7) ( W=6.70, P < 0.001). The color, thickness, blood vessel distribution and softness were significantly reduced compared with those before surgery ( P< 0.01). All patients were followed up for 12-18 months (mean, 14 months) after hair transplantation. The survival rate of hair in hard and thin scar area was 68.2% (22.7 FUs/cm 2/33.3 FUs/cm 2) to 89.7% (26.1 FUs/cm 2/29.1 FUs/cm 2), with an average of 81.3%. In 32 patients, scalp scars were completely covered. The scalp scar of 25 patients was basically covered. Twenty-nine patients were very satisfied with the result of the operation, and 28 patients were satisfied. Conclusion:The high survival rate of hair transplantation can be obtained by injecting fat under the hard and/or thin scalp scars before hair transplantation, which is an effective method to repair scalp scars.