Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

OBJECTIVE: A new three-dimensional(3D) classification of posterior cruciate ligament (PCL) tibial avulsion fracture based on computed tomography(CT) features was established and the significance in clinical treatment was explored in this study. METHODS: From May 2013 to November 2023, 43 cases of PCL tibial avulsion fracture in the Second Hospital of Jilin University were analyzed retrospectively, including 29 males and 14 females, aged (34.3±8.5) years. According to traditional Meyers and McKeever classification, 3 cases were typeⅠ;2 cases of typeⅡ;38 cases were type Ⅲ. Based on the characteristics of CT images, 43 patients were given specific treatment strategies and followed up to evaluate the curative effect. According to the degree of fracture displacement, involved range and the integrity of fracture block demonstrated by CT images, the new three-dimensional classification of PCL avulsion fracture was established. Kappa coefficient was used for consistency test. RESULTS: A new 3D classification of PCL tibial avulsion fracture was established. TypeⅠwas the non-displaced fracture (displacement degree ≤3 mm), in which typeⅠa was the avulsion range limited in the posterior intercondylar fossa, and Ib was the avulsion range beyond the posterior intercondylar fossa. TypeⅡrepresented the displaced fracture in the posterior intercondylar fossa (avulsion limited to the posterior intercondylar fossa and fracture displacement>3 mm), in which typeⅡa represented a slight displacement with a intact broken block and the posterior elevation of the avulsion (hinge mechanism), typeⅡb represented the complete separation of fracture ends with a intact fracture block, and typeⅡc was the comminuted fracture. Type Ⅲ was the displaced fracture beyond the posterior intercondylar fossa (avulsion involving the articular surface of the tibial plateau or the intercondylar ridge and the degree of displacement > 3 mm), among which type Ⅲa was the simple fracture with intact broken block, type Ⅲb represented the comminuted fracture, and type Ⅲc was the complex fracture with tibial plateau fracture. According to this new 3D classification, 43 patients were classified as type Ia in 2 cases and typeⅠb in 1 case;typeⅡa in 2 cases, typeⅡb in 15 cases and typeⅡc in 7 cases;type Ⅲa in 2 cases, type Ⅲb in 5 cases and type Ⅲc in 9 cases. All the 43 cases in this study achieved bone union. At the last follow-up, according to the hospital for special surgery knee score(HSS)evaluation system for the knee joint function, 27 cases were excellent, 11 cases were good, 5 cases were fair. The average Kappa value of inter-observer reliability in the first stage was 0.793, and the second stage was 0.855. The average Kappa value of the whole stage was 0.839, indicating high level of consistency. The average Kappa value of intra-observer reliability was 0.893, indicating high level of consistency. CONCLUSION The 3D classification of PCL tibial avulsion fracture is intuitive, demonstrating a high level of reliability. It has a certain guiding significance for the selection of clinical treatment methods, and it is suggested to be promoted and applied as a new classification system in clinical practice.
Humans ; Male ; Female ; Posterior Cruciate Ligament/surgery* ; Adult ; Tibial Fractures/classification* ; Tomography, X-Ray Computed ; Middle Aged ; Retrospective Studies ; Fractures, Avulsion/classification* ; Imaging, Three-Dimensional ; Young Adult

Objective:To compare clinical efficacy and safety of peripheral to central pruning of apocrine sweat glands versus along small incision of apocrine sweat glands in the treatment of axillary bromhidrosis.Methods:A prospective randomized controlled study method was used to recruit patients with armpit odor admitted to the Department of Aesthetic and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from June to October 2022. The patients were divided into the experimental group (underwent peripheral to central pruning of apocrine sweat glands with small incision of axillary fold under direct view) and the control group (apocrine sweat glands were cut off along the direction of small incisions) by randomization. The occurrence of postoperative complications such as hematoma, infection, skin necrosis, delayed incision healing, scar and skin contracture were observed in both groups, and the incidence rate was calculated. The surgical effect was evaluated 6 months after the operation, and the number of cured, markedly effective, and ineffective sides was counted, and the cure rate and effective rate were calculated; the satisfaction was investigated and divided into two options: satisfactory and dissatisfied, and the satisfaction rate was calculated. Count data were analyzed using the chi-square test. P<0.05 indicated that the difference was statistically significant. Results:A total of 52 patients were recruited. Experimental group, 26 patients (52 side), 6 male, 20 women, aged 18-31 years, mean of 22 years; control group, 26 patients (52 side), 6 male, 20 women, aged 18-47 years, mean of 21 years. The incidence of postoperative complications in the experimental group was 3.85% (2 / 52), which was lower than 19.23% (10/52) of the control group, with statistically significant difference ( χ2=3.98, P=0.046), in which the flap necrosis, local contracture, scarring and delayed incision healing were better than the control group. The postoperative response rate in both groups was 100%(52/52), but the cure rate in the experimental group was higher than the control group [96.15% (50/52) vs. 80.77% (42/52)], with a significant difference ( χ2=6.03, P=0.014). The satisfaction rate of the experimental group was 96.15% (50/52), higher than the 82.69% (43/52) of the control group, and the difference was statistically significant ( χ2=4.92, P=0.026). Conclusion:Compared with the traditional small incision of peripheral to central pruning method and the traditional small incision of apocrine sweat glands method, the cure rate of the former is higher, which can effectively protect the skin flap dermis and subdermal vascular network around the incision, reduce postoperative skin necrosis and scar, and improve patient satisfaction.

Objective:To compare clinical efficacy and safety of peripheral to central pruning of apocrine sweat glands versus along small incision of apocrine sweat glands in the treatment of axillary bromhidrosis.Methods:A prospective randomized controlled study method was used to recruit patients with armpit odor admitted to the Department of Aesthetic and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from June to October 2022. The patients were divided into the experimental group (underwent peripheral to central pruning of apocrine sweat glands with small incision of axillary fold under direct view) and the control group (apocrine sweat glands were cut off along the direction of small incisions) by randomization. The occurrence of postoperative complications such as hematoma, infection, skin necrosis, delayed incision healing, scar and skin contracture were observed in both groups, and the incidence rate was calculated. The surgical effect was evaluated 6 months after the operation, and the number of cured, markedly effective, and ineffective sides was counted, and the cure rate and effective rate were calculated; the satisfaction was investigated and divided into two options: satisfactory and dissatisfied, and the satisfaction rate was calculated. Count data were analyzed using the chi-square test. P<0.05 indicated that the difference was statistically significant. Results:A total of 52 patients were recruited. Experimental group, 26 patients (52 side), 6 male, 20 women, aged 18-31 years, mean of 22 years; control group, 26 patients (52 side), 6 male, 20 women, aged 18-47 years, mean of 21 years. The incidence of postoperative complications in the experimental group was 3.85% (2 / 52), which was lower than 19.23% (10/52) of the control group, with statistically significant difference ( χ2=3.98, P=0.046), in which the flap necrosis, local contracture, scarring and delayed incision healing were better than the control group. The postoperative response rate in both groups was 100%(52/52), but the cure rate in the experimental group was higher than the control group [96.15% (50/52) vs. 80.77% (42/52)], with a significant difference ( χ2=6.03, P=0.014). The satisfaction rate of the experimental group was 96.15% (50/52), higher than the 82.69% (43/52) of the control group, and the difference was statistically significant ( χ2=4.92, P=0.026). Conclusion:Compared with the traditional small incision of peripheral to central pruning method and the traditional small incision of apocrine sweat glands method, the cure rate of the former is higher, which can effectively protect the skin flap dermis and subdermal vascular network around the incision, reduce postoperative skin necrosis and scar, and improve patient satisfaction.

Objective:To investigate the effects of oral probiotics on intestinal microbiota and cognitive dysfunction in breast cancer chemotherapy patients. Methods:Thirty breast cancer patients who received anthracycline chemotherapy between December 2021 and June 2022 in the Department of Oncology, the First Affiliated Hospital of Bengbu Medical University were included in this study. The patients were randomly divided into the observation and control groups (15 cases per group). During chemotherapy, the observation group was additionally given oral probiotics. The fecal microbiota compositions before and after chemotherapy were detected using 16S rDNA sequencing. The changes in patients' subjective and objective cognitive function levels were evaluated by Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog), respectively. Results:The microbiota diversity, as indicated by the Chao, Ace, Shannon and Simpson indices, showed no significant difference between two groups (P>0.05). As compared with the control group, the relative abundance of the genus Actinomyces in the feces was significantly higher than in the observation group (P<0.05). By contrast, the relative abundance of the genera Acetoanaerobium, Lachnospiracea_incertae_sedis, and unclassified_Frankineae bacteria was significantly lower in the observation group (P<0.05). The total scores of the objective and subjective cognitive function as well as the scores of each dimension in both groups were markedly decreased after chemotherapy (P<0.05). The scores in the observation group were higher than those in the control group after chemotherapy (P<0.05). During chemotherapy, the presence of the gastrointestinal adverse reactions (constipation, nausea and vomiting, diarrhea and abdominal distension) in the observation group were significantly lower than in control group (P<0.05). Conclusion:Oral probiotics could improve the cognitive impairment and reduce the presence of the gastrointestinal side effects in the breast cancer patients receiving chemotherapy, which may be caused by modulating the intestinal microbiota.

Fluorescent carbon dots(CDs)were synthesized via a solvothermal method with citric acid and urea as raw materials,and ethylene glycol as reaction solvent.The micromorphology,crystal structure,elemental composition,surface functional group,and optical property of as-synthesized CDs were characterized.The excitation-dependent fluorescence property of CDs was investigated,and the effects of synthesis conditions including reaction temperature,reaction time and raw materials on excitation and emission wavelengths of the CDs were also discussed.Then,a series of CDs-based fluorescent composites were prepared by combining CDs with starch,nano-silica,montmorillonite,kaoline,kieselguhr and magnesium oxide,respectively.Finally,the CDs-starch composites were used for latent fingerprint development on smooth substrates,and the qualitative as well as quantitative evaluation of the contrast,sensitivity and selectivity in fingerprint development were also made.Enhanced development of latent fingerprints was thus achieved by the aid of the excitation-dependent fluorescence property of CDs-starch composite combined with the optical filtering technique,which could decrease the background noise interference to a great extent.Experimental results showed that,the contrast between fingerprint(developing signal)and substrate(background noise)was obvious,exhibiting a strong contrast;the minutiae of papillary ridges were clear,indicating a high sensitivity;the adsorption between CDs-starch composites and fingerprint residues was specific,showing a good selectivity.

A serious of rare earth luminescent micro/nano-materials with various properties were synthesized via chemical method for fluorescent development of latent fingerprints(LFPs).Three evaluation indexes namely contrast,sensitivity and selectivity were introduced to evaluate the effects of LFP development.Quantitative formulas for calculating the contrast,sensitivity and selectivity were further put forward,and a quality evaluation system based on Python was thus established.In addition,the objective evaluation value was finally confirmed to be consistent with the subjective visual judgment.The reproducibility of this evaluation method was finally confirmed.The effects of luminescence intensity and color of developing materials on the contrast,particle size of developing materials on the sensitivity,and micromorphology and surface property of developing materials on the selectivity were discussed in detail.Five effective ways were also proposed to promote the quality of LFP development,such as increasing the luminescence intensity,tuning the luminescence color,decreasing the particle size,adjusting the micromorphology,and modifying the surface property.This quality evaluation system based on Python could evaluate the effects of LFP development objectively,accurately and comprehensively,exhibiting easy operability,high efficiency,sensitive response,accurate and reliable results,and wide applicability,which would provide beneficial references for the reasonable selection of LFP development methods as well as objective evaluation of evidence value.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes and related risk factors in children with mycoplasma pneumoniae pneumonia(MPP).Methods The clinical data of 420 children with MPP admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected.The clinical data included gender,age,history of respiratory tract diseases,TCM syndromes,MPP classification,cough duration,fever duration,fever peak value,laboratory indicators of C-reactive protein(CRP),procalcitonin(PCT)and lactate dehydrogenase(LDH),and the complication of infection.SPSS 26.0 software was used for data statistics,and then the distribution of TCM syndromes in children with MPP and its correlation with various clinical data,as well as the related risk factors of MPP with different classification and various TCM syndromes were explored.Results(1)Among the 420 children with MPP,there were 283 cases(67.4％)of mild MPP,76 cases(18.1％)of refractory MPP,and 61 cases(14.5％)of severe MPP.For the distribution of TCM syndromes,there were 152 cases(36.2％)of wind-heat obstructing the lung syndrome,141 cases(33.6％)of phlegm-heat obstructing the lung syndrome,77 cases(18.3％)of damp-heat obstructing the lung syndrome,25 cases(6.0％)of toxin-heat obstructing the lung syndrome,16 cases(3.8％)of lung-spleen qi deficiency syndrome,and 9 cases(2.1％)of yin deficiency and lung heat syndrome.For the classification of infection,there were 295 cases(70.2％)of simple mycoplasma pneumoniae(MP)infection and 125 cases(29.8％)of mixed infection.(2)There were statistically significant differences in age stratification and visit season among MPP children with different TCM syndromes(P＜0.01),while no significant differences were shown in the gender,history of respiratory tract diseases,and the complication of infection(P＞0.05).(3)There were statistically significant differences in the visit season,history of respiratory tract diseases,and the complication of infection among the children with various MPP types(P＜0.05),while no significant differences were shown in the gender and age stratification(P＞0.05).(4)There were statistically significant differences in laboratory indicators of CRP and PCT and in the symptoms of cough duration,fever duration and fever peak among MPP children with different TCM syndromes(P＜0.05 or P＜0.01).(5)Significant differences were presented in laboratory indicators of PCT and LDH and in the symptoms of cough duration,fever duration and fever peak value among the children with different MPP types(P＜0.05 or P＜0.01).(6)Multivariate logistic regression analysis showed that CRP level ≥10.5 mg/L and wind-heat obstructing the lung syndrome were the independent risk factors for mild MPP(P＜0.05 or P＜0.01);fever duration≥7 days,cough duration ≥ 12 days and phlegm-heat obstructing the lung syndrome were the independent risk factors for refractory MPP(P＜0.05 or P＜0.01);cough duration ≥ 12 days,mixed infection and toxin-heat obstructing the lung syndrome were the independent risk factors for severe MPP(P＜0.01).Conclusion The results indicated that the classification MPP in children is predominated by mild MPP,and their TCM syndrome types is predominated by wind-heat obstructing the lung syndrome.The proportions of refractory MPP and damp-heat obstructing the lung syndrome increase significantly in autumn,which may be related to the characteristics of regional environment and circuit qi.The increase of CRP level and fever peak may be related to phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome.In clinic,attention should be paid to the early use of heat-clearing and phlegm-resolving drugs or heat-clearing and toxin-removing drugs;children with the history of respiratory tract diseases and mixed infections are more likely to develop into severe MPP,and the physicians should be alert clinically.Wind-heat obstructing the lung syndrome,phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome are the independent risk factor separately for mild MPP,refractory MPP and severe MPP,which requires timely intervention to prevent mild MPP from developing into refractory MPP or severe MPP in clinic.

BACKGROUND:At present,wrist protection products designed in and outside China have not solved the contradiction between protecting the wrist joint from injury and maintaining the flexible movement of the wrist joint. OBJECTIVE:To investigate the biomechanical mechanism of dorsiflexion injury of the wrist joint in elderly people after falls,and to provide a biomechanical basis for the prevention and treatment of wrist injury in elderly people after falls. METHODS:A 65-year-old man was selected to obtain the original data by uninterrupted CT scan of the middle and lower 2/3 of his left forearm up to the end of the finger.A finite element model of wrist dorsiflexion was established using ANSYS 12.0 finite element software.The palm surface of the model was constrained,and the model at a velocity load of 2 m/s in the direction of vertical downward was given to simulate the injury state of the palm when the elderly fall.The stress distribution of the soft tissues and bones of the wrist joint and the change of the stress with time were observed after the load was applied. RESULTS AND CONCLUSION:(1)A realistic and effective finite element model of the dorsal extension position of the wrist joint of the elderly was established.The soft tissue stresses were mainly concentrated in the small fissure of the palm and the dorsal side of the wrist after loading.The skeletal stresses were mainly concentrated in the lower end of the ulnar radius dorsally.The stresses in the lower end of the radius were the greatest.The palmar stresses were mainly concentrated in the middle and lower 1/3 of the radius and the hook bone.The stress distribution of the ulnar radius was asymmetric,and the stresses in the radius were more concentrated.(2)The results of the study are consistent with the clinical situation of a fallen wrist injury in elderly people,and can be used to explain the mechanism of wrist dorsiflexion injury,which can provide the biomechanical basis for the design of wrist protection devices that can be used to prevent wrist injury induced by falling and the treatment of wrist injury in elderly people.

OBJECTIVES: Existing evidence suggests that miscarriage and stillbirth are associated with an increased risk of stroke in women. However, the impact of these events on stroke mortality remains unclear. This study aimed to elucidate the potential association between miscarriage and stillbirth and stroke mortality in women. METHODS: We employed a competing risk model using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between miscarriage/stillbirth and stroke death. Death from other causes was considered as a competing risk, and we conducted a subgroup analysis to explore the potential impact. RESULTS: Our study included 68,629 women for miscarriage and 65,343 women for stillbirth. No significant association was observed between miscarriage and stroke mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.84 to 1.10; p=0.58). While a single stillbirth did not show a significant association (HR, 0.81; 95% CI, 0.57 to 1.15; p=0.23), recurrent stillbirth (≥2) was associated with a significantly increased risk of stroke mortality compared to women with no stillbirths (HR, 2.24; 95% CI, 1.45 to 3.46; p<0.001). CONCLUSIONS Our findings suggest that recurrent stillbirth, but not single events, is associated with an elevated risk of stroke mortality in women. Further research is warranted to clarify the underlying mechanisms and potential long-term health implications of recurrent pregnancy loss.