With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

This study systematically analyzed the global research landscape, technological composition, and core patents in the field of networks target and network pharmacology, and proposes further suggestions based on the IncoPat patent citation database and VOSviewer bibliometric network visualization tool. Using patent literature metrics and scientific knowledge mapping method, technological innovation pathways, research hotspots, and future directions in this field were further revealed. In particular, this field is moving towards data-driven, intelligent, and systematic approaches. Patent analysis indicated that most patent applications in this domain focused on traditional Chinese medicine(TCM), which have provided key engineering technical approaches to explore and solve complex problems of TCM. By integrating big data and artificial intelligence technologies, network targets and network pharmacology have conferred high-precision screening and quality control of key components and targets in herbal formulations and prescriptions, accelerating the clinical translation and industrialization of TCM-based new drugs and health products with medicine-food homology. Therefore, it is essential to optimize the patent protection system and establish integrated technology platforms in this field for ensuring the competitiveness of technological achievements in research and clinical application. These efforts will advance the widespread application and high-quality development of TCM modernization, precision medicine, and innovative drug discovery.
Bibliometrics ; Patents as Topic ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology/trends* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To explore early curative effect of upper joint capsule reconstruction combined with biceps tendon transposition in treating irreparable rotator cuff tears. METHODS: From October 2019 to March 2021, 16 patients with irreparable rotator cuff tear were underwent arthroscopic autogenous semitendinosus tendon transplantation for upper articular capsule reconstruction combined with biceps tendon transposition, included 12 males and 4 females, aged from 53 to 72 years old with an average of (62.13±5.35) years old; 3 patients on the left side and 13 patients on the right side. All patients had preoperatively limited joint mobility, resting pain, and mobility pain, and had a history of failure to respond to conservative treatment for more than 8 months. The duration of preoperative symptoms ranged from 45 to 144 months with an average of (85.25±32.08) months. Visual analogue scale (VAS) of shoulder pain, University of California Los Angeles (UCLA) score, Constant-Murley score, active and passive motion of shoulder joint were compared before operation and 2 years after operation, complications were recorded. RESULTS: All 16 patients were followed up for 21 to 32 months with an average of (24.25±3.57) months. There were no complications such as incision infection, vascular and nerve injury, retear occurred. VAS, UCLA and Constant-Murley scores were improved from (5.75±1.18), (11.88±3.38) and (33.38±9.34) before operation to (1.13±0.89), (32.56±2.71), (89.06±6.25) at 2 years after operation (P<0.05). Anterior flexion, abduction, lateral external rotation and lateral internal rotation of shoulder joint were improved from (79.75±21.36) °, (62.06±10.49) °, (19.19±5.41) °, (3.04±0.21) °, respectively to (156.94±13.18) °, (116.19±12.59) °, (42.63±6.07) °, (8.16±0.64) ° at 2 years after operation. Anterior flexion, abduction, lateral lateral rotation and lateral internal rotation of shoulder joint were improved from (116.28±21.47) °, (107.12±9.67) °, (27.62±4.70) °, (4.21±0.41) °, respectively to (165.28±7.15) °, (153.34±4.69) °, (52.46±4.46) °, (9.68±0.68) ° at 2 years after operation, and the difference was statistically significant (P<0.05). CONCLUSION Arthroscopic autograft of semitendinosus tendon combined with transposition of biceps tendon could achieve satisfactory early clinical results in treating patients with irreparable rotator cuff tear, which is a reliable and effective surgical method.
Humans ; Male ; Female ; Middle Aged ; Aged ; Arthroscopy/methods* ; Rotator Cuff Injuries/physiopathology* ; Plastic Surgery Procedures/methods* ; Range of Motion, Articular ; Shoulder Joint/surgery* ; Tendon Transfer

OBJECTIVE: To explore clinical effect of autologous osteochondral transplantation (AOT) in the treatment of recurrent anterior dislocation of the shoulder joint with glenoid cartilage defect in rabbits by establishing a model of recurrent anterior dislocation of the shoulder joint with < 20% glenoid cartilage defect in rabbits. METHODS: Twenty-four male New Zealand white rabbits, aged 6-month-old, weighed (2.69±0.17) kg were selected. The labrum of shoulder joint of rabbits was artificially destroyed to establish a model of recurrent anterior dislocation of shoulder joint with cartilage defect. They were divided into AOT surgery group and simple suture group, with 12 rabbits in each group. AOT group were underwent AOT surgery, while simple suture group was treated with simple Bankart suture for recurrent shoulder joint dislocation. At 6 and 12 weeks after operation, 6 rabbits between two groups were sacrificed for sampling. The dietary conditions, activity conditions, mental states of rabbits and healing conditions of grafts in the specimens were observed and compared between two groups. HE staining was used to observe cell creep, cell morphology, inflammatory cell infiltration, fibrochondrocytes and their arrangement. Masson staining was used to observe the formation and arrangement of collagen fibers; Safrane-green staining was used to observe the regeneration of articular cartilage, subchondral bone and bone tissue. Bone mineral density (BMD), bone volume (BV) and trabecular thickness (Tb.Th) between two groups were measured by Micro-CT to evaluate the remodeling of shoulder glenoid bone defects by autologous osteochondral cartilage. RESULTS: After different surgical interventions were carried out in both groups of rabbits, at 6 weeks after the operation, the abduction, extension, internal rotation and external rotation of the shoulder joint on the operated side showed limited range of motion compared with the contralateral side, while adduction and forward flexion showed no obvious abnormalities compared with the contralateral side. At 12 weeks after operation, the range motion of tshoulder joints in both groups of rabbits had returned to the state before modeling. The effects of HE staining, Masson staining and safrane-green staining at 12 weeks after operation in both groups were stronger than the staining results at 6 weeks after operation. Moreover, the results of HE staining, Masson staining and safranin fixation green staining in AOT group at 6 and 12 weeks after operation were all higher than those in simple suture group. Micro-CT scan results at 6 and 12 weeks after operation showed that BMD (0.427±0.014), (0.466±0.032) g·cm-3, BV(116.171±3.527), (159.327±3.500) mm3, and Tb.Th (0.230±0.006), (0.285±0.009) mm in AOT group, which were higher than those of simple suture group in BMD(0.358±0.011), (0.384±0.096) g·cm-3, BV(72.657±3.903), (118.713±3.860) mm3, and Tb.Th(0.204±0.009), (0.243±0.007) mm;and the differences were statistically significant (P<0.05). CONCLUSION AOT procedure could effectively promote osteogenesis and fibrocartilage regeneration in the cartilage defect area of the shoulder glenoid <20%, which is conducive to reshaping the structure of the shoulder glenoid.
Animals ; Rabbits ; Male ; Transplantation, Autologous ; Cartilage, Articular/injuries* ; Shoulder Dislocation/physiopathology* ; Bone Transplantation ; Shoulder Joint/surgery*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore the clinical effect of composite skin transplantation combined with systemic rehabilitation in the treatment of extensive scar contracture deformity around the popliteal fossa in children after burns.Methods:A retrospective observational research method was adopted. Seventeen children with extensive scar contracture deformities around the popliteal fossa after burns who met the inclusion criteria and were admitted to the First Affiliated Hospital of Air Force Military Medical University from March 2018 to April 2022 were selected. Among them, there were 10 males and 7 females, aged 2-11 years, with scar contracture deformities lasting from 10 months to 9 years, all located around the popliteal fossa, 10 cases of right popliteal fossa, 5 cases of left popliteal fossa, 2 cases of bilateral popliteal fossa, scars around the popliteal fossa result in a knee joint extension angle of only 95° to 115°. The scar contracture during surgery was thoroughly released, joint mobility was restored, so as to form a secondary wound range of 10 cm×8 cm-20 cm×13 cm. In stage Ⅰ, after completely releasing the scar contracture, the wound was covered with negative pressure closure drainage (VSD) for 2-3 days. In stage Ⅱ, a large autologous blade thick scalp and allogeneic decellularized dermal matrix composite graft was performed to repair the wound around the popliteal fossa. After 8-10 days of surgery, the dressing was changed to check the survival of the skin graft. One week after the skin graft survived, a 12 month orderly knee joint function training was conducted under the guidance of a rehabilitation therapist. Postoperative sequential treatment with a combination of strong pulsed light and ultra pulsed carbon dioxide lattice laser for 5-7 courses of significant scar hyperplasia in the skin graft area and edges.Results:15 cases of pediatric patients had good skin graft survival; One patient developed a wound due to partial displacement of the transplanted autologous scalp, and one patient developed a plasma swelling under the limb graft, which was drained through an opening. Two patients underwent dressing changes for 3 weeks before the wound healed. After follow-up for 6 to 36 months, the elasticity and appearance of the skin graft were similar to those of a medium thickness skin graft. Children with knee joint contracture were able to fully extend to 180°, and knee joint function was significantly improved. There was no scar formation or hair loss in the donor skin area.Conclusions:The combination of composite skin transplantation and systematic rehabilitation has a good effect on the treatment of extensive scar contracture around the popliteal fossa in children after burns, avoiding the problem of scars left in the donor area due to autologous skin grafting.

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Objective To summarize the clinical experience of pulmonary lobectomy by uniportal video-assisted thoracoscope in parallel position.Methods The clinical data of 90 patients who underwent uniportal video-assisted thoracoscopic lobectomy in Zhongshan Hospital(Xiamen Branch),Fudan University were retrospectively analyzed.Among them,41 patients underwent lobectomy by uniportal thoracoscope in parallel position,and 49 patients underwent lobectomy by uniportal thoracoscope in non-parallel position.The perioperative related indicators of the two groups were compared.Results There was no significant statistical difference between the parallel uniportal thoracoscopic group and the non-parallel uniportal thoracoscopic group in terms of operation time[(135.2±18.1)min vs.(132.7±25.6)min],intraoperative blood loss[(100.1±27.2)mL vs.(117.3±33.5)mL],postperative extubation time[(3.0±0.7)d vs.(3.1±0.9)d],hospitalization time after operation[(4.3±1.3)d vs.(4.8±1.5)d]and relapse rate after surgery in 3 year(7.32%vs.10.20%).Conclusion Lobectomy by uniportal thoracoscope in parallel position was safe and feasible in technique.