The abnormal accumulation, structural change, and spread of tau protein in the brain are now considered important factors in the progression of Alzheimer’s disease (AD) and many other tau-related neurodegenerative diseases. Clinical and pathological studies have shown that the amount and distribution of abnormal tau protein are closely related to synaptic damage, neuronal loss, and cognitive decline. Therefore, tau protein has become an important target for disease-modifying therapy. However, tau is difficult to target because it has no fixed structure, lacks a clear active site, undergoes many post-translational modifications, and forms different abnormal structures in different diseases and disease stages. Therefore, the effective and selective removal of harmful tau species is both a major opportunity and a major challenge in drug discovery for neurodegenerative diseases. Proteolysis-targeting chimeras (PROTACs) offer a new strategy to deal with this problem. Unlike traditional inhibitors, PROTACs do not simply block protein function. Instead, they bring the target protein close to an E3 ubiquitin ligase, which leads to ubiquitination and degradation of the target protein by the proteasome. This event-driven mechanism may be especially useful for disease-related proteins such as tau protein, which are hard to inhibit with traditional small molecules. In recent years, tau protein-targeting PROTACs and related degradation strategies have shown promising effects in cell and animal models. These effects include reducing abnormal tau protein levels, lowering synaptic toxicity, regulating disease-related signaling pathways, and improving behavioral or cognitive outcomes. These studies support targeted tau protein degradation as a promising therapeutic approach, although many problems still need to be solved before clinical use. In this review, we summarize recent progress in the development of tau protein-targeting PROTACs and discuss the main factors that affect their design and activity. We focus on the choice of tau protein-binding ligands, their binding sites, and their ability to recognize abnormal tau protein rather than normal tau protein. We also discuss the selection of E3 ligase recruiters, linker length and structure, ternary complex formation, and structure-activity relationships that influence degradation potency and selectivity. In addition, we introduce new strategies beyond traditional proteasomal degradation, including the regulation of tau protein phosphorylation and autophagy-based clearance. These approaches may be more suitable for different tau species or different stages of disease. A major challenge for tau protein-targeting PROTACs is delivery to the central nervous system. Many PROTACs have high molecular mass, large polar surface area, flexible structures, and may be removed by efflux transporters. As a result, they often have poor ability to cross the blood-brain barrier and may not reach enough free drug levels in the brain. Therefore, the therapeutic potential of tau protein-targeting PROTACs depends not only on their ability to degrade tau protein in vitro, but also on whether they can achieve long-lasting, selective, and safe target engagement in important brain regions after practical administration. Future studies should focus on improving selectivity for abnormal tau protein, understanding E3 ligase function in neural cells, designing brain-penetrant molecules, developing better delivery methods, and testing these drugs in models that better reflect human disease. Overall, tau protein-targeting PROTACs are a promising and fast-developing strategy for treating tau-related diseases. However, their successful clinical translation will require progress in chemical biology, medicinal chemistry, neuroscience, drug delivery, and translational medicine.

Objective:To determine the epidemic characteristics of polymyxin resistance ( mcr) genes of Enterobacteriales colonized in patients admitted to hospitals in Zhejiang, Henan, Gansu and Shandong provinces in China in 2023. Methods:A comprehensive collection of 667 fecal specimens from patients admitted to five medical facilities across the provinces of Zhejiang, Henan, Gansu, and Shandong in 2023 was collected. Epidemiological characteristics of Enterobacteriales bacteria positive for the mcr gene were examined, employing techniques such as microbial culturing, using agarose gel electrophoresis, PCR, whole-genome sequencing, bioinformatics analysis, and the induction of antimicrobial resistance. Statistical analysis was subsequently applied to the gathered data. Results:Among 667 fecal samples from admitted patients, five samples were positive for mcr gene, with a carrier rate of 0.75%(5/667), and from two of the samples, two different strains carrying the mcr gene were isolated, respectively. A total of seven strains of Enterobacteriales carrying the mcr gene were detected, of which four strains carried mcr-1 gene and three strains carried mcr-9 gene. The positive isolates included three strains of Escherichia coli, one strain of Citrobacter braakii, Citrobacter freundii, one strain of Klebsiella pneumoniae, and one strain of Enterobacter hormaechei. The seven mcr positive strains were isolated from two distinct geographical locations within China, with four from Zhejiang Province and three from Henan Province. After whole-genome sequencing, it was found that the 16S rRNA sequences of the three strains of mcr-1 positive Escherichia coli had high homology. The three isolates of mcr-9 positive strains preserved a significant degree of homology within the mcr-9 and wbuC regions. Following polymyxin exposure, there was a marked difference in the growth kinetics of the ZJ-307, HN-11-1, and HN-135 strains post-induction compared to their pre-induction growth rates, and their motility capacity was reduced. Conclusions:The prevalence of Enterobacteriales harboring the mcr gene is minimal among hospitalized patients. However, it is noteworthy that these genes are prone to horizontal transfer. They can move into drug-resistant strains, which may have elevate minimum inhibitory concentration(MIC). Resistance to polymyxin can alter the bacterial growth rate and motility, potentially impacting the MIC of other antibiotics, thereby complicating clinical management. Consequently, it is imperative to focus on the proactive screening of susceptible populations to prevent the further dissemination of plasmid-mediated polymyxin resistance among clinically significant gram-negative bacterial pathogens.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in right-hand ultrasound physicians and identify contributing factors for carpal tunnel syndrome (CTS) .Methods:From May 2023 to February 2025, 188 ultrasound physicians from 15 hospitals in Heilongjiang Province were surveyed using questionnaires to assess their prevalence of wrist-specific mechanical strain disorders (WMSDs) over the past year. Neurophysiological tests were conducted, and logistic regression analysis was performed to identify factors affecting the right carpal tunnel syndrome (CTS) .Results:The prevalence of wrist WMSDs among ultrasound physicians was 48.4% (91/188) . Multivariate logistic regression analysis revealed that age and frequent probe pressure application were associated with 2.14-fold and 4.04-fold increased CTS risk, respectively.Conclusion:Enhance society's attention to the health of noise-exposed physiciansand providing a foundation for implementing targeted interventions.

Objective:To explore the predictive value of positive lymph node ratio (LNR) for tumor specific mortality in cervical cancer patients after surgery for 5 years.Methods:A total of 120 patients with cervical cancer with lymph node metastasis admitted to the Affiliated Hospital of Jining Medical University from January 2017 to December 2018 were retrospectively selected. The patients were followed up for 5 years and divided into a death group (48 cases) and a control group (72 cases) according to whether tumor-specific death occurred after surgery. The main clinical features and LNR differences between the two groups were compared. The predictive value of LNR for tumor-specific death was analyzed by receiver operating characteristic(ROC) curve, and the risk factors for tumor-specific death in patients with cervical cancer at 5 years after surgery were analyzed by multivariate Logistic retrospective analysis.Results:The low differentiation rate and the rate of periuterine invasion, the rate of pelvic invasion, the number of lymph node metastasis and LNR in the death group were higher than those in the control group: 47.92%(23/48) vs.16.67%(12/72), 58.33%(28/48) vs. 27.78%(20/72), 29.17%(14/48) vs. 9.72%(7/72), (9.35 ± 4.04) nodes vs. (5.07 ± 2.74) nodes, (46.01 ± 19.66)% vs.(23.04 ± 13.76)%, there were statistical differences ( P<0.05). The results of ROC curve analysis showed that LNR was valuable in predicting the tumor specific mortality in cervical cancer patients after surgery within 5 years, with areas under the curve of 0.832 (95% CI 0.760 - 0.905). The results of multivariate Logistic retrospective analysis showed that LNR>30.43%, poorly differentiated cancer, parametrial infiltration and pelvic infiltration were independent risk factors for tumor specific death in cervical cancer patients at 5 years after surgery ( P<0.05). Conclusions:The LNR has a high predictive value for tumor specific mortality in cervical cancer patients after 5 years of surgery, and can be used as a predictive indicator for patient's prognosis.

Objective:To investigate the trends in detection, treatment, and outcomes of rifampicin-resistant tuberculosis (TB) in Jiangsu Province from 2013 to 2023, assess the effectiveness of control policies and measures for drug-resistant TB, and provide evidence for better control of drug-resistant TB.Methods:Data and indicators related to the screening, diagnosis, treatment, and outcomes of rifampicin-resistant TB in Jiangsu Province from 2013 to 2023 were obtained from the Tuberculosis Management Information System. The Joinpoint regression method was employed to analyze the trends over this period, and annual percent change (APC) and average annual percent change (AAPC) were calculated. A comparative analysis was also conducted to evaluate the changes before and after implementing relevant policies and measures.Results:From 2013 to 2023, the number of registered rifampicin-resistant TB patients in Jiangsu Province showed a consistent upward trend (APC=AAPC=1.45%, P=0.035). The screening rates for drug resistance among new TB patients in high-risk groups and the proportion of molecular biological testing for drug resistance all exhibited increasing trends, with a notable turning point occurring in 2018. The trend of the treatment enrollment rate for rifampicin-resistant TB patients experienced a significant shift in 2020, showing a marked increase from 2013 to 2020 (APC=12.91%, P=0.008). The treatment success rate of rifampicin-resistant TB patients also showed a significant upward trend after a turning point in 2020 (APC=9.94%, P=0.004). Conclusion:From 2013 to 2023, significant progress was seen in preventing and treating rifampicin-resistant TB in Jiangsu Province, with relevant policies and measures proving to be highly effective.

Objective:To investigate the correlation between leucine-rich α2 glycoprotein (LRG) and endoscopic activity in patients with Crohn′s disease (CD), based on the assessment of inflammation in small intestinal lesion by double-balloon enteroscope (DBE).Methods:From 15 August 2022 to 22 August 2023, the clinical data of 139 patients with small bowel CD diagnosed by DBE at the First Affiliated Hospital of Anhui Medical University were prospectively collected, which included fecal calprotectin (FC), C-reactive protein (CRP), white blood cell count, hemoglobin, albumin, Crohn′s disease activity index (CDAI), and simple endoscopic score for Crohn′s disease (SES-CD). According to the SES-CD, endoscopic activity was classified as mucosal healing (0), endoscopic remission (0 to 2), mild activity (3 to 6), moderate activity (7 to 15), and severe activity (≥16). LRG levels were detected in all patients. Spearman rank correlation was used to analyze the correlation between LRG, clinical biochemical parameters and endoscopic scores. Receiver operating characteristic curve (ROC) was performed to determine the optimal cut-off value of LRG for evaluating endoscopic mucosal healing. Mann-Whitney U test, Kruskal-Wallis H test, and Bonferroni corrected test were used for statistical analysis. Results:Among 139 patients with small bowel CD, the LRG level was 17.3 (13.0, 25.2) mg/L, and SES-CD was 5 (1, 9); 32 patients achieved mucosal healing, 50 patients achieved endoscopic remission; 39 patients had mild activity, 40 patients had moderate activity, and 10 patients had severe activity. The SES-CD was negatively correlated with both hemoglobin and albumin ( r=-0.177 (95% confidence interval, 95% CI: -0.334 to -0.011), -0.293 (95% CI: -0.438 to -0.133)), with statistical significance ( P=0.037, <0.001). The SES-CD was positively correlated with CRP, CDAI, LRG and FC ( r=0.344 (95% CI: 0.188 to 0.482), 0.429 (95% CI: 0.282 to 0.556), 0.525 (95% CI: 0.393 to 0.636), 0.661 (95% CI: 0.556 to 0.745)), with statistical significant (all P<0.001). For the 64 small bowel CD patients with CRP in the normal reference value, SES-CD was positively correlated with CDAI, LRG and FC ( r=0.296 (95% CI: 0.054 to 0.505), 0.364 (95% CI: 0.129 to 0.559), 0.547 (95% CI: 0.348 to 0.699)), with statistical significance ( P=0.017, =0.003, <0.001). The LRG level of patients with endoscopic mucosal healing was significantly lower than that of patients with endoscopic remission (11.5 (10.1, 17.2) mg/L vs. 17.3 (13.4, 23.5) mg/L), with statistical significance ( Z=-3.25, P<0.001). ROC analysis showed that the area under the curve (AUC) of LRG in predicting endoscopic mucosal healing was 0.81 (95% CI: 0.73 to 0.89), with an optimal cut-off value of 15.27 mg/L. The sensitivity, specificity, positive predictive value and negative predictive value were 0.757, 0.718, 0.900 and 0.469, respectively. The accuracy of the combination of LRG and FC (AUC was 0.88, 95% CI: 0.82 to 0.94) in predicting endoscopic mucosal healing was higher than that of LRG alone (AUC was 0.81, 95% CI: 0.73 to 0.89), and the difference was statistically significant ( P=0.011). Conclusion:Based on the results of DBE, LRG may be a reliable biomarker for predicting endoscopic remission and mucosal healing in patients with small bowel CD.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Aim To investigate the role of miR-130b-3p in regulating the USP47/NLRP3 inflammasome in airway remodeling associated with asthma and to explore its potential therapeutic value in asthma treat-ment.Methods An OVA-induced asthma mouse mod-el was established,and intervention with miR-130b-3p agomir was performed.Histological staining,quantita-tive real-time PCR,Western blot,immunofluorescence and flow cytometry were used to analyze the effects of miR-130b-3p on the expression of USP47,NLRP3,and related inflammatory factors,as well as the inflamma-some activity.Results miR-130b-3p was significantly downregulated in asthmatic mice,and its intervention significantly inhibited airway epithelial damage,inflam-matory cell infiltration,and collagen deposition.Addi-tionally,miR-130b-3p targeted USP47 and indirectly suppressed NLRP3 expression,leading to reduced in-flammasome activity and alleviated asthma-related in-flammatory responses.Conclusion miR-130b-3p re-duces asthma-related inflammatory responses by down-regulating USP47 expression and indirectly inhibiting NLRP3 inflammasome activity.

Objective:To investigate the prevalence of work-related musculoskeletal disorders (WMSDs) in right-hand ultrasound physicians and identify contributing factors for carpal tunnel syndrome (CTS) .Methods:From May 2023 to February 2025, 188 ultrasound physicians from 15 hospitals in Heilongjiang Province were surveyed using questionnaires to assess their prevalence of wrist-specific mechanical strain disorders (WMSDs) over the past year. Neurophysiological tests were conducted, and logistic regression analysis was performed to identify factors affecting the right carpal tunnel syndrome (CTS) .Results:The prevalence of wrist WMSDs among ultrasound physicians was 48.4% (91/188) . Multivariate logistic regression analysis revealed that age and frequent probe pressure application were associated with 2.14-fold and 4.04-fold increased CTS risk, respectively.Conclusion:Enhance society's attention to the health of noise-exposed physiciansand providing a foundation for implementing targeted interventions.