This paper systematically reviews the current status of integrated traditional Chinese and western medicine in the treatment of Helicobacter pylori （Hp） infection， as well as recent progress in clinical and basic research both in China and internationally. It summarizes the advantages of traditional Chinese medicine （TCM） in Hp infection management， including improving Hp eradication rates， enhancing antibiotic sensitivity， reducing antimicrobial resistance， decreasing drug-related adverse effects， and ameliorating gastric mucosal lesions. These advantages are particularly evident in patients who are intolerant to bismuth-containing regimens， those with refractory Hp infection， and individuals with precancerous gastric lesions. An integrated， whole-process management approach and individualized， staged comprehensive treatment strategies combining TCM and western medicine are proposed for Hp infection. Future prevention and control of Hp infection should adopt an integrative Chinese-western medical strategy， emphasizing prevention， strengthening primary care， implementing proactive long-term monitoring， optimizing screening strategies， and advancing the development of novel technologies and mechanistic studies of Chinese herbal interventions. These efforts aim to provide a theoretical basis and practical pathways for the establishment and improvement of Hp infection prevention and control systems.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective To systematically evaluate the safety and efficacy of Kangfuxin liquid combined with adenosine monophosphate in the treatment of paediatric herpetic stomatitis.Methods Randomised controlled trials(RCTs)of Kangfuxin liquid combined with adenosine monophosphate for the treatment of paediatric herpetic stomatitis were searched in various databases,and Meta-analysis was performed using RevMan 5.4 software.Results A total of 12 RCTs with a sample size of 1,094 cases were included.Meta-analysis showed that the combination of Kangfuxin liquid with adenosine monophosphate significantly increased[RR=1.21,95%CI(1.16,1.28),P<0.000 01]the overall clinical efficacy rate of paediatric herpetic stomatitis.Compared with the conventional antiviral treatment group with adenosine monophosphate,the incidence of adverse events was lower in the Kangfuxin liquid group[RR=0.26,95%CI(0.14,0.51),P<0.000 01].In addition,the Kangfuxin liquid group could effectively shorten the time for herpes disappearance(skin lesion healing),pain disappearance,fever reduction,salivation disappearance and recovery of diet(P<0.05),and had advantages in promoting the recovery of lymphocytes(CD3+,CD4+,CD8+,and CD4+/CD8+),serological levels(CRP,TNF-α,WBC,IL-10,VEGF,EGF,and IL-6)(P<0.05).Conclusion Kangfuxin liquid combined with adenosine monophosphate has the better efficacy and safety in the treatment of paediatric herpetic stomatitis,and has advantages in shortening the symptomatic recovery time and improving the indicators of lymphocyte and serological levels in paediatric herpetic stomatitis.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective:To investigate the risk factors of hypoparathyroidism (HPT) and hypocalcemia in patients undergoing total thyroidectomy (TT), and to explore the changes of parathyroid hormone and blood calcium after TT.Methods:The clinical data of 101 patients undergoing TT from November 2018 to September 2022 in the First Hospital of Hebei Medical University were retrospectively analyzed. The basic clinical data were recorded. The blood calcium and parathyroid hormone levels were measured before surgery and 1 d, 1 week after surgery. The occurrence of postoperative hypocalcemia was recorded. According to postoperative parathyroid hormone level, the patients were divided into control group (normal parathyroid function) and HPT group (reduced parathyroid hormone level). The patients with postoperative hypocalcemia symptoms were classified as the hypocalcemia symptoms group, and the patients without postoperative hypocalcemia symptoms were classified as the non-hypocalcemia symptoms group. Multivariate Logistic regression was used to analyze the independent risk factors of HPT and hypocalcemia in TT patients.Results:The postoperative parathyroid hormone level decreased in 41 cases (HPT group) and normal in 60 cases (control group). There were 24 patients with postoperative hypocalcemia symptoms (hypocalcemia symptoms group) and 77 patients without postoperative hypocalcemia symptoms (non-hypocalcemia symptoms group). The rate of using bipolar electric coagulation forceps in HPT group was significantly lower than that in control group: 31.71% (13/41) vs. 76.67% (46/60), while the rate of central lymph node dissection was significantly higher than that in control group: 82.93% (34/41) vs. 60.00% (36/60), and there were statistical differences ( P<0.01 and <0.05). Multivariate Logistic regression analysis result showed that TT combined with unilateral or bilateral central lymph node dissection was an independent risk factor for HPT in TT patients ( OR = 1.706 and 1.501, 95% CI 1.019 to 2.856 and 1.052 to 2.140, P<0.05). The preoperative serum calcium, postoperative serum calcium and postoperative parathyroid hormone in hypocalcemia symptoms group were significantly lower than those in hypocalcemia symptoms group: (2.32 ± 0.11) mmol/L vs. (2.37 ± 0.11) mmol/L, (2.16 ± 0.21) mmol/L vs. (2.25 ± 0.18) mmol/L and 3.00 (1.00, 5.45) ng/L vs. 19.90 (8.50, 33.80) ng/L, and there were statistical differences ( P<0.05 or <0.01). Multivariate Logistic regression analysis result showed that postoperative parathyroid hormone was an independent risk factor of hypocalcemia symptoms in TT patients ( OR = 0.927, 95% CI 0.883 to 0.974, P<0.01). In patients with HPT, the blood calcium at 1 week after surgery was significantly lower than that at 1 d after surgery: (2.07 ± 0.19) mmol/L vs. (2.17 ± 0.25) mmol/L, and there was statistical difference ( t = 2.05, P<0.05); the parathyroid hormone at 1 week after surgery was significantly higher than that at 1 d after surgery: 8.30 (3.55, 19.55) ng/L vs. 3.60 (1.00, 6.85) ng/L, and there was statistical difference ( Z = - 3.78, P<0.01). Conclusions:When performing TT, standardizing the surgical techniques, reducing unnecessary central lymph node dissection, and using bipolar electric coagulation forceps as much as possible can help to reduce the occurrence of postoperative HPT. The levels of postoperative parathyroid hormone and blood calcium should be promptly detected, the change of both should be given attention, and do a good job in preventing and treating hypocalcemia.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.