The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

ObjectiveTo explore the possible mechanism of Yigan Fupi Prescription （抑肝扶脾方， YFP） in treating diarrhea-type irritable bowel syndrome （IBS-D） by investigating the AKT/mTOR signaling pathway. MethodsSixty SD rats were randomly divided into control group， model group， YFP low-， medium-， and high-dose group， and pinaverium bromide group， with 10 rats in each group. All groups but the control group， were subjected to 21 days of tail-clamping stimulation and 14 days of senna leaf gavage to establish a liver stagnation and spleen deficiency-type IBS-D rat model. After successful modeling， the YFP low-， medium-， and high-dose group were administered 0.96， 1.93， and 3.87 g/（kg·d） of the prescription， respectively. The pinaverium bromide group was given 13.5 mg/（kg·d）， while the control and model groups were given 10 ml/（kg·d） distilled water. All groups were administered once daily for 14 consecutive days. General conditions of the rats were recorded during the experiment， and after modeling and drug administration， body weight， Bristol stool score， abdominal withdrawal reflex （AWR） score， and histo pathology of colon tissue were observed under HE staining. ELISA was used to detect serum levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Immunofluorescence was employed to detect the levels of AKT/mTOR pathway-related proteins including phosphorylated AKT （p-AKT）/AKT and phosphorylated mTOR （p-mTOR）/mTOR in the colon tissue. Western Blotting was used to detect the levels of autophagy-related proteins， including UNC-51-like kinase 1 （ULK1）， Beclin1 and LC3， and tight junction proteins including Occludin and ZO-1 in the colon tissue. ResultsAfter modeling， compared to the control group， the body weight of rats in the other groups decreased， and Bristol stool scores， as well as AWR scores under 20， 40， 60， and 80 mmHg increased （P＜0.05 or P＜0.01）. After drug administration， compared to the control group， the model group showed reduced body weight， decreased ULK1， Beclin1， LC3Ⅱ/LC3Ⅰ， Occludin， and ZO-1 protein levels in the colon tissue （P＜0.05 or P＜0.01）， and increased Bristol stool scores， AWR scores， serum TNF-α， IL-1β， and IL-6 levels， as well as p-AKT/AKT and p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. Pathological results showed a significant reduction in goblet cells in the upper part of the glandular layer of the colon， with mild inflammatory cell infiltration. The submucosal collagen fibers were dissolved， with unclear boundaries， pale staining， and microvascular congestion and dilation. Compared with the model group， the YFP low-， medium-， and high-dose group and the pinaverium bromide group showed increased body weight， Beclin1， Occludin， and LC3Ⅱ/LC3Ⅰ protein levels （P＜0.05 or P＜0.01）， and decreased Bristol stool scores， AWR scores under 40， 60， and 80 mmHg， serum IL-1β， IL-6， TNF-α levels， and p-AKT/AKT， p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. The pathological morphology of the rats in the YFP groups and pinaverium bromide group showed varying degrees of improvement. Compared with the pinaverium bromide group， the YFP low- and medium-dose group showed increased AWR scores under 20， 40， and 60 mmHg （P＜0.05）. The YFP low-dose group had reduced TNF-α， IL-1β， and IL-6 levels， and increased p-mTOR/mTOR protein relative expression levels occured in all YFP groups （P＜0.05）. Compared with the YFP low-dose group， the YFP high-dose group and pinaverium bromide group showed decreased AWR scores under different pressure levels and reduced p-AKT/AKT protein relative expression levels， while the YFP medium- and high-dose group had elevated serum TNF-α， IL-1β levels and reduced p-mTOR/mTOR protein relative expression levels （P＜0.05）. ConclusionYFP can effectively improve the pathological injury of colon tissue in IBS-D model rats with liver stagnation and spleen deficiency， reduce Bristol stool and AWR scores， and its mechanism may be related to reducing level of inflammatory factors and inhibiting AKT/mTOR pathway-related proteins in colon tissue， thereby enhancing the expression of autophagy-related proteins in the colon tissue.

Objective To analyze the correlation between serum cystatin C (Cys-C) and bone turnover markers in elderly patients with type 2 diabetes mellitus (T2DM) and osteoporosis. Methods A retrospective analysis was conducted on the data of 320 elderly patients with T2DM admitted to Huai'an First People's Hospital from August 2021 to June 2024. Patients were divided into the osteoporosis group and the non-osteoporosis group according to whether they had osteoporosis. General information, bone turnover markers, and serum Cys-C levels were collected from all patients. The data were compared between the two groups to analyze the influencing factors of osteoporosis in elderly patients with T2DM and the correlation between serum Cys-C and bone turnover markers. Results The levels of total cholesterol and LDL-C in the osteoporosis group were higher than those in the non-osteoporosis group, and the bone mineral density was lower than that in the non-osteoporosis group (P<0.05). The levels of TPINP, β-CTX, and Cys-C in the osteoporosis group were higher than those in the non-osteoporosis group, and 25-OH-D3 level was lower than that in the non-osteoporosis group (P<0.05). Serum Cys-C was positively correlated with TPINP and β-CTX, and negatively correlated with 25-OH-D₃ (P<0.05). Multivariate logistic regression analysis found that total cholesterol, LDL-C, TPINP, β-CTX, 25-OH-D₃, and Cys-C were factors influencing osteoporosis in elderly patients with T2DM (P<0.05). Conclusion Serum Cys-C levels in elderly patients with T2DM and osteoporosis are elevated. There is a significant correlation between Cys-C level and bone turnover markers.

BACKGROUND:Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke,and its mechanism of action is still unclear. OBJECTIVE:To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats. METHODS:Fifty Sprague-Dawley rats were divided into sham-operated group,model group,positive control group,high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method,with 10 rats in each group.Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group.Administration in each group started on the 3rd day after surgery,and the rats in the positive control group were intraperitoneally injected with edaravone injection(6 mg/kg),the rats in the high-and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively,and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline.After 14 days of continuous treatment in each group,the pathological changes in rat brain tissue were observed,and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected. RESULTS AND CONCLUSION:Compared with the sham-operated group,the volume of cerebral infarction became larger in the model group;the structure of brain tissue was loose,irregular cavities could be observed,and the number of neurons was reduced and irregularly arranged;the positive expression of NLRP3 inflammasome increased(P<0.01);and the protein and mRNA expression levels of Toll-like receptor 4,myeloid differentiation factor 88,apoptosis-associated speck-like protein containing a caspase-recruitment domain,Caspase-1,and interleukin-1β increased(P<0.01).Compared with the model group,the volume of cerebral infarction became smaller in the high-and low-dose gastrodin groups;the neurons were regularly arranged,increased in number,and uniformly distributed;the positive expression of NLRP3 inflammasome was decreased(P<0.05);the protein and mRNA expression levels of Toll-like receptor 4,myeloid differentiation factor 88,apoptosis-associated speck-like protein containing a caspase-recruitment domain,Caspase-1,and interleukin-1β were decreased in the high-dose gastrodin group(P<0.01);Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group,and the protein and mRNA expression of the other inflammatory response-associated factors decreased(P<0.05,P<0.01).To conclude,gastrodin attenuates inflammatory injury in ischemic stroke rats,and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression.

The climate on the plateau is characterized by hypobaria and hypoxia,where the natural environment is harsh,which poses a serious threat to the health and combativeness of troops.As a vital organ of the human body,the kidney has a complex vascular structure,large oxygen consumption,and is vulnerable to damage from hypoxia and other factors.This paper outlines the special changes of renal function and current diagnosis and treatment of kidney injury by taking into consideration the actual conditions on the plateau and renal blood and oxygen supply.Meanwhile,related countermeasures are recommended to facilitate the prevention and treatment of kidney injury in warfare on the plateau.

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

Large cell neuroendocrine carcinoma(LCNEC)of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer.In recent years,the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing.Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens.However,there is no consensual agreement of its therapy.Recently,immune checkpoint inhibitors(ICIs)has provided a new option for LCNEC patients based on some retrospective research data and case reports.In this review,we aimed to summarize the epidemiological characteristics,standard therapy,the advances of molecular subtypes and clinical applications of ICIs of LCNEC,so as to provide optimal systemic clinical decision-making for LCNEC patients.

Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Objective:To analyze the changing trends of the epidemic characteristics of human brucellosis in Hangzhou City, and to provide a basis for further formulating prevention and control measures.Methods:The epidemic data of brucellosis in Hangzhou City from 2004 to 2021 were collected from the "China Disease Control and Prevention Information System" and the annual reports, compilations and summaries of prevention and control work of brucellosis in Hangzhou City, and the epidemiological characteristics and trends of brucellosis cases in Hangzhou City from 2004 to 2009, 2010 to 2015, and 2016 to 2021 were compared and analyzed.Results:A total of 186 cases of brucellosis were diagnosed in Hangzhou City from 2004 to 2021, with an average annual incidence rate of 0.151/100 000, ranging from 0.016/100 000 to 0.286/100 000. The incidence rate showed a stage-by-stage upward trend from 2004 to 2009, 2010 to 2015, and 2016 to 2021 ( Z = 3.15, P = 0.002). The age of onset of brucellosis cases was predominantly 18 - 60 years old, accounting for 78.49% (146/186). The male-to-female ratio was 2.10∶1.00 (126∶60). The occupational and non-occupational populations accounted for 62.90% (117/186) and 37.10% (69/186), respectively, with the proportion of non-occupational cases in the three stages being 28.57%, 23.29% and 51.76%, showing an increasing trend (χ 2trend = 9.85, P = 0.002). The regional distribution was dominated by Yuhang District, accounting for 55.91% (104/186), followed by Jianggan District (9.14%, 17/186) and Fuyang District (7.53%, 14/186). The number of brucellosis epidemic counties (cities, districts) increased from 6 to 9. The seasonal analysis showed that the proportion of cases from January to June decreased from 84.93% (23/28) from 2004 to 2009 to 54.12% (46/85) from 2016 to 2021. The proportion of infection from outside the province in the three stages was 0, 10.96% and 27.38%, respectively, showing an upward trend (χ 2trend = 18.16, P < 0.001), the main infected areas were Henan Province, Heilongjiang Province, and Inner Mongolia Autonomous Region. In clinical symptoms and signs, the incidence of muscle and joint pain and low back pain increased from 60.71% (17/28) and 10.71% (3/28) from 2004 to 2009, respectively, to 83.53% (71/85) and 25.88% (22/85) from 2016 to 2021, both showing an upward trend (χ 2trend = 9.92, 4.67, P = 0.002, 0.031). Conclusions:The incidence of human brucellosis in Hangzhou City is on the rise, and the number of cases of non-occupational population has increased significantly in recent years. The sheep breeding places have gradually become the high incidence areas of brucellosis in Hangzhou City. It is recommended to strengthen the promotion and education of knowledge on brucellosis prevention among the general public, and focus on actively monitoring human brucellosis in high-risk areas.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.