There are practical and cost-effective opportunities for the prevention and early intervention of periodontal disease, a common oral condition. Depression and anxiety represent major global mental health challenges, and they are characterized by high prevalence rates and an elevated suicide risk. Their clinical management is complicated by extended treatment timelines and substantial healthcare costs. Accumulating evidence demonstrates a statistically significant bidirectional association between periodontal disease and depression/anxiety disorders. However, established clinical pathways integrating these conditions remain lacking. This review presents a comprehensive analysis of current research examining the relationship between periodontal disease and mood disorders, specifically depression and anxiety. This study explored the bidirectional mechanisms within the microbiota-oral-brain axis, which includes both periodontal disease inducing neuroinflammation through pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) activating the TLR-4/NF-κB signaling pathway, and depression and anxiety leading to “glucocorticoid resistance” through hypothalamic-pituitary-adrenal (HPA) axis dysregulation, thus causing dual immune dysfunction that exacerbates periodontal tissue destruction, as well as the mechanisms by which biological, psychological, and social factors contribute to the bidirectional association between periodontal disease and depression/anxiety. We propose implementing bidirectional referral protocols between dental and psychiatric services in clinical practice, incorporating mental health screening tools, such as Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7(GAD-7), for patients with moderate-to-severe periodontal disease, and incorporating periodontal examination into routine assessment during psychiatric services. This multidisciplinary approach aims to break the vicious circle between these conditions and provide clinicians with pragmatic intervention strategies.

ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Objective To analyze the electromyography(EMG)characteristics of high-level male speed climbers using Tomoa skip technique,and provide a theoretical basis for the determination of special strength training methods and means.Methods Ten male speed climbers at national first level or above were recruited,and their kinematics and surface EMG signal data using Tomoa skip technique during climbing the official route were collected.Results For using Tomoa skip technique,the order of the main muscle contribution rate for high-level male speed climbers was biceps brachii,triceps brachii,flexor digitorum superficialis,latissimus dorsi,anterior tibial,vastus lateralis,gluteus maximus,medial head of gastrocnemius muscle.The sum of all muscle contribution rates of the left side,the contribution rate of biceps brachii and triceps brachii were significantly lower than that of the right side(P＜0 05).The contribution rate of medial head of left gastrocnemius muscle was significantly higher than that of right side(P＜0.05).The level of activation of the left biceps brachii was significantly lower than that of the right side(P＜0.05).The co-contraction indexes of left elbow joint and ankle joint,right elbow joint and ankle joint were 0.93±0.21,1.33±0.14,0.72±0.10,2.08±0.59,respectively.The co-contraction level of the left elbow joint and ankle joint was significantly higher than that of the right side(P＜0.05).Conclusions High-level male speed climbers using Tomoa skip technique showed obvious EMG characteristics,and the contribution rate of the upper limb muscles and latissimus dorsi were higher than that of the lower limb.The activation mode of elbow joint was dominated by biceps brachii,and that of ankle joint was dominated by anterior tibial muscle.There exsited differences between the left and right limbs in coordinated movement modes.The difference of contribution rate and activation level of the upper limb between the left and right side was more than that of the lower limb.

Objective To evaluate the application efficacy of structured symptom intervention program in patients with chronic kidney disease(CKD)during the peri-dialysis period.Methods A non-simultaneous control study was conducted on 151 peri-dialysis outpatients having not yet initiated dialysis and being followed up who were subjected with convenience sampling from Department of Nephrology of Second Affiliated Hospital of Army Medical University from April to September 2024.According to the time period of their visits,the patients who visited from April to June 2024 were assigned into a control group(n=75),and those from July to September 2024 into an experimental group(n=76).The control group received conventional symptom intervention(telephone symptom reporting+health education),while the experimental group received the intervention as the control group and a structured symptom intervention program covering 4 evidence-based modules:symptom identification,assessment,intervention,and outcome.The efficacy of above treatments was evaluated before and at 3 months after intervention.Dialysis symptom index was used to assess the degree of symptom distress and the number of symptoms.MOS 36-Item Short Form Health Survey(SF-36)was employed to evaluate the quality of life.The differences in clinical indicators and endpoint events were compared between the 2 groups after intervention.Results The experimental group obtained more significant reduction in the total score of symptom distress than the control group(P=0.021).After intervention,the number of symptoms was decreased in both groups(P<0.001),but no statistical difference was observed between the groups.The score of mental health dimension in SF-36 was obviously improved in the experimental group(P=0.004),which was notably better than that in the control group(P=0.033).The experimental group exhibited significantly higher prealbumin level than the control group(P=0.019),and stable albumin level,which was significantly decreased in the control group(P=0.035).The incidence of endpoint events was remarkably lower in the experimental group than the control group(P=0.028).Conclusion The structured symptom intervention program implements intervention through a closed-loop symptom module,which can effectively alleviate the symptom distress of patients during the peri-dialysis period,improve mental health and reduce the short-term risk for endpoint events.

Hereditary liver diseases refer to liver metabolic disorders caused by gene mutations. The existing clinical treatments are mostly symptomatic therapies，delaying liver damage and improving patients' lives. With the development of gene therapy technology，it has become possible to treat genetic diseases by modifying known gene mutations. This review briefly introduces several common gene therapies（including recombinant adeno-associated virus vectors，CRISPR/Cas9，antisense oligonucleotides，lipid nano particle-mRNA），and discusses the latest research progress，ongoing challenges and potential solutions of gene therapy for hereditary liver diseases through the relevant preclinical studies and drug clinical trials of hereditary liver diseases. In order to promote the further development of gene therapy and provide reference for the treatment of other complex diseases.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Objective:To summarize the clinical and genetic features of neuroinflammation, autoinflammation, splenomegaly and anemia (NASA) syndrome and investigate the pathogenic mechanism.Methods:The clinical data of 2 patients diagnosed with NASA syndrome at Department of Pediatrics, Peking Union Medical College Hospital were retrospectively analyzed. Variants were identified by gene panel sequencing and confirmed by Sanger sequencing. The function of IRAK4 gene variants was studied in vitro.Results:Among the 2 patients, case 1 was an 8-year-old girl and case 2 was a 10-year-old boy. Both patients presented in early childhood with anemia and hepatosplenomegaly. Case 1 was also experienced recurrent seizures. Laboratory examinations showed elevated inflammatory markers and neuroimaging revealed bilateral basal ganglia calcification. In case 2, anemia and inflammation markers were well controlled after treatment with tocilizumab, while case 1 succumbed to recurrent seizures. Genetic tests verified compound heterozygous variants in IRAK4 gene: case 1 carries a nonsense variant c.592G>T (p.G198X) and a missense variant c.248A>C (p.D83A), which were respectively from the parents; case 2 carries a c.831+3A>G variant and a frameshift variant c.540delT (p.F180Lfs*26), and the former was inherited from the father and the latter from the mother. The reverse transcription and Sanger sequencing results confirmed that c.831+3A>G variant led to exon 7 skipping. In vitro studies indicated that c.592G>T, c.540delT and c.831+3A>G variants resulted in truncated interleukin-1 receptor-associated kinase-4 (IRAK4) protein while c.248A>C do not cause changes in IRAK4 protein expression level and protein length.Conclusions:NASA syndrome should be considered in children with early-onset anemia, hepatosplenomegaly, recurrent seizures, elevated inflammatory markers and intracranial calcification. IRAK4 gene variants may lead to impaired anti-inflammatory function of IRAK4 protein, contributing to the autoinflammatory phenotype.

Objective:To investigate the ability to diagnose, treat and manage kidney disease in Shanghai community health service centers.Methods:This was a cross-sectional survey. An online questionnaire survey was conducted in November 2023 among 248 Shanghai community health service centers and 2 140 general practitioners in Shanghai. The main topics of the institutional research were the kidney disease-related inspection items that medical institutions could carry out, the kidney disease diagnosis and treatment drugs, the kidney disease grass-roots management training, the opening of kidney disease clinics and the establishment of kidney disease standard diagnosis and treatment records. The main topics of the survey of general practitioners were general information, standardized diagnosis and management measures of kidney disease, knowledge based on the diagnosis and treatment guidelines of chronic kidney disease, and difficulties in standardized management of kidney disease.Results:Among the laboratory examination items in Shanghai community health service centers, the rates of routine urine (99.60%, 247 centers), renal function (95.16%, 236 centers) and urinary microalbumin (89.11%, 229 centers) were high. Among the imaging examinations, B-ultrasound of urinary system had the highest rate (92.34%, 229 centers). The preparation rate of kidney disease drugs varied widely among the centers, and the preparation rate of Chinese drugs such as Jinshuibao, nephritis Kangfu tablet and Shenshuaining was more than 90%. Sixty-six (26.61%) community health service centers had established kidney disease clinics. The overall accuracy rate of community general practitioners was 63.81% (13 656/21 400), of which the accuracy rate for diagnosis and screening method, referral indication and emergency dialysis indication was more than 85%, but the accuracy rate for drug treatment and careful medication was low at 28.93% (1 238/4 280) and 33.22% (711/2 140), respectively. There was a willingness for Community general practitioners to provide all aspects of life guidance for patients with kidney disease, but for patients with end-stage renal disease replacement therapy, there was a preference for this to be provided by the appropriate specialist.Conclusions:The community health service centers in Shanghai has already had the basic conditions for the management of kidney disease in terms of basic examination and testing equipment, drugs, etc. The community general practitioners have a certain knowledge of kidney disease, and the drug treatment needs to be strengthened.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.