Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

Atherosclerosis (AS) remains the core pathological basis underlying the high incidence and high rates of mortality and disability associated with cardiovascular disease (CVD) worldwide. Its essence is not merely lipid deposition, but rather an immune-mediated disease of the vascular wall characterized by an interplay of lipid metabolism disorders and chronic inflammation, with damage to vascular endothelial cells serving as the initiating event. As the disease progresses, it involves complex synergistic interactions among various cellular components, including endothelial cells, macrophages, and inflammatory cells, ultimately leading to plaque formation, instability, and even fatal thrombotic events. In recent years, the central driving role of lipid metabolic reprogramming in the progression of AS has garnered increasing attention from the scientific community. Among the vast array of lipid molecules, long-chain fatty acids (LCFAs) have become a primary focus of research due to their exceptional physiological functions. Traditional views have primarily emphasized the basic physiological functions of LCFAs: serving as highly efficient energy substrates through mitochondrial β-oxidation and acting as key structural components of cellular phospholipid membranes. However, emerging evidence clearly indicates that the functions of LCFAs extend far beyond those of mere metabolic fuel. They also act as potent bioactive signaling molecules, playing an indispensable multidimensional role in the pathogenesis of AS. Equally noteworthy and representing a paradigm shift in cardiovascular research is the emerging theory of the “gut-heart axis”. This theoretical framework views the human gut microbiota—comprising trillions of microorganisms—as a critical and metabolically active “bioreactor”. A wealth of clinical and multi-cohort epidemiological studies have conclusively demonstrated that imbalances in the composition and function of the gut microbiota are highly correlated with the clinical risk and severity of AS. Within this axis, the gut microbiota serves as the primary processing hub for dietary lipids. It actively participates in the digestion and biochemical remodeling of LCFAs, thereby altering their saturation and chemical structure and generating a wide variety of gut microbial metabolites. The effects of these gut-derived lipid metabolites extend far beyond the local intestinal microenvironment. Upon entering the bloodstream, these circulating microbiota metabolites act as endocrine signals. Given the extreme complexity of the underlying mechanisms, a comprehensive elucidation of the synergistic and bidirectional interactions between LCFAs and the gut microbiota in vascular pathology is particularly urgent. Therefore, this article aims to provide a systematic review of the multidimensional regulatory mechanisms of LCFAs and their associated gut microbiota metabolites in the onset, progression, and clinical manifestations of AS. By thoroughly exploring the interaction patterns within the “LCFAs-gut microbiota-AS” triad, this review seeks to fundamentally expand our understanding of the pathogenesis of CVDs. More importantly, translating these mechanistic insights into clinical practice holds tremendous promise. We hope to provide a solid theoretical foundation for the future development of novel AS prevention and treatment strategies based on non-traditional approaches. These include precision nutritional interventions (i.e., dietary lipid intake plans tailored to an individual’s unique microbiome profile) and targeted microbiome modulation therapies (such as next-generation probiotics, prebiotics, or specific metabolite supplements). Targeting the gut as a “reactor” to treat vascular wall lesions represents a promising direction for future cardiovascular medicine.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the awareness of clinical practice guidelines (referred to as "guidelines") and experts consensus (referred to as "consensus") among otorhinolaryngology head and neck surgery medical staff, and to analyze the effectiveness of the ninth guideline methodology workshop.Methods:Self-designed survey questionnaires were used to conduct two surveys among otorhinolaryngology head and neck surgery medical staff who participated in the ninth guideline methodology workshop held in Chengdu from Jannuary 10 to 11, 2025, both before and after the training, to assess their awareness and knowledge of guideline and consensus development methodology. The effectiveness of the training was evaluated using the paired chi-square test.Results:A total of 77 peoples (95.06%), who participated in the ninth guideline methodology workshop, completed the survey questionnaires both before and after the training. One-third of the respondents reported a relatively good to very good understanding of guideline and consensus development. The overall methodology of the guidelines and consensus they had participated in developing still showed room for improvement. After the methodology training, the score rate for each test question significantly increased compared to before the training ( P<0.05), and the distribution trend of the total scores changed markedly (Before the training, 71 people scored less than 60 points, 4 people scored 60 points, and 2 people scored 70 points. After the training, only 1 person scored less than 60 points, 1 person scored 60 points, and 75 people scored between 70 and 100 points, of which 21 people scored 100 points). Conclusion:The awareness of guideline and consensus development methodology among otorhinolaryngology head and neck surgery medical staff still has room for improvement. The guideline methodology workshop can enhance participants′ mastery of guideline and consensus development methodology.

Objective To assess the clinical efficacy of intravitreal anti-vascular endothelial growth factor(VEGF)agents plus panretinal photocoagulation(PRP)for treating young and middle-aged patients with proliferative diabetic reti-nopathy(PDR).Methods A retrospective case study was conducted on young and middle-aged PDR patients presenting to the Ophthalmology Department of Shaanxi Provincial People's Hospital between January 1,2021 and October 1,2024.The patients were divided into three groups according to Chinese Clinical Guidelines for Diabetic Retinopathy(2022):se-vere non-proliferative diabetic retinopathy(NPDR),early proliferative diabetic retinopathy(E-PDR)and fibrous prolifera-tive diabetic retinopathy(F-PDR).A total of 53 patients(94 eyes)were included in this study,and the mean age was(41.66±10.24)year old.There were 17 cases(31 eyes)in the NPDR group,18 cases(33 eyes)in the E-PDR group,and 18 cases(30 eyes)in the F-PDR group.All the patients were treated with the intravitreal injection of anti-VEGF agents(0.5 mg ranibizumab)about 3.5 mm from the sclerocorneal limbus at the inferior temporal sector,once a month,for three consecutive months.Routine PRP treatment was given 1 week after the first injection.Best-corrected visual acuity[BCVA(logMAR)],intraocular pressure,slit-lamp,slit-lamp fundus,optos fundus photography and OCT examinations were per-formed.The central macular thickness(CMT),average macular thickness(AMT),and the incidence of diabetic vitreous hemorrhage and emerging epiretinal membrane were recorded 1 month and 3 months after the first injection.Results Pa-tients in the F-PDR group were younger than those in NPDR and E-PDR groups(all P＜0.05).The BCVA values of eyes in all the three groups increased to varying degrees after 3 months of treatment,compared with those before treatment(all P＜0.05).The eyes in the F-PDR group had poorer vision than those in NPDR and E-PDR groups after 3 months of treat-ment(all P＜0.05).CMT and AMT decreased in all groups after 3 months of treatment,compared with those before treat-ment(all P＜0.05).No significant difference was found in CMT and AMT among the three groups at the same period(all P＞0.05).Eyes in the F-PDR group had higher risk of diabetic vitreous hemorrhage and emerging epiretinal membrane than those in NPDR and E-PDR groups 3 months after treatment(all P＜0.05).Conclusion Intravitreal anti-VEGF therapy combined with PRP can effectively slow the progression of PDR and improve vision acuity in young and middle-aged pa-tients.PDR patients with fibrovascular proliferation are at higher risk of diabetic vitreous hemorrhage and emerging epireti-nal membrane during the treatment with intravitreal anti-VEGF therapy plus PRP.These patients need a close follow-up,and vitrectomy should be performed in a timely manner to relieve vitreous traction when necessary.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Objective To sort,summarize,and introduce key terms related to guideline reporting,evaluation,dissemination,implementation,and updating.Methods We systematically searched guideline de-velopment manuals and methodological literature from database inception to October 25,2024.Terms related to guideline reporting,updating,evaluation,and implementation were extracted,standardized,and finalized through a structured consensus process.Results A total of 13 guideline manuals and 32 methodological articles were included,yielding 14 core terms with standardized definitions.Conclusions This article introduces key terms such as reporting standards,external review,and research gaps across guideline development phases to promote concept application and deepen readers'understanding of guideline development.

Objective:To explore the clinical effect of endoscopic radical thyroidectomy via three-port gasless intermuscular approach.Methods:This is a retrospective cohort study. The data of 148 patients who underwent radical thyroidectomy at the Fourth General Surgery Department of the Second Affiliated Hospital of Harbin Medical University from January to June 2024 were retrospectively analyzed. There were 31 males and 117 females,aging (43.5±9.6) years (range: 21 to 64 years). The surgical method was selected according to the needs and wishes of patients. Among them, 77 cases underwent endoscopic radical thyroidectomy via unilateral three-port gasless intermuscular approach (three-port gasless group),and 71 cases underwent unilateral conventional open radical thyroidectomy(open group). The surgical technique exploration curve of the three-port gasless group was drawn based on the operation time and the number of lymph node dissections,and the technical exploration period and the technical maturity period were divided. The clinical data of the cases in the three-port gasless group and the open group were compared during the technical maturity period. The independent sample t test was used to compare the quantitative data between the two groups, and the χ2 test or Fisher exact probability method was used to compare the categorical data, respectively. Results:According to the technical exploration curve,there were 11 cases in the technical exploration period of the three-port gasless group,and 66 cases in the technical maturity period. In the technical mature period,the injury rate of temporary recurrent laryngeal nerve in the three-port gasless group was 1.5% (1/65),and the number of lymph node dissections was 5.9±3.5(range:0 to 14),which was not statistically significant compared with 4.4% (3/68) and 5.8±3.7(range:0 to 16) in the open group (all P>0.05). In the technical mature period,the operation time of the three-port gasless group was (39.2±6.2)minutes(range:30 to 55 minutes) and the postoperative drainage volume was (57.6±11.8) ml(range:30 to 90 ml),which were lower than those of the open group((67.8±13.9) minutes (range: 30 to 105 minutes) and (82.9±22.4)ml(range:50 to 175 ml)),and the differences were statistically significant ( t=15.303, 8.177, both P>0.05). During the technical maturity period,the postoperative hospital stay in the three-port gasless group was (3.2±0.4)days(range:3 to 4 days), which was not statistically different from that of the open group((3.2±0.4)days(range:3 to 5 days))( P>0.05). The incision satisfaction of patients in the three-port gasless group one month after the operation was higher than that of the control group (100% vs. 62.0%) ( P<0.01). Conclusion:Compared with open surgery,endoscopic radical thyroidectomy via three-port gasless intermuscular approach has certain advantages in terms of operation time, postoperative drainage volume and patient cosmetic satisfaction.

To introduce and analyze guideline terminology related to clinical question formulation, evidence retrieval and appraisal, and recommendation development.