BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， processing and other aspects of Euphorbiae Pekinensis Radix（EPR） by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， so as to provide a basis for the development and utilization of famous classical formulas containing this herbal medicine. According to research， EPR was first recorded in the Shennong Bencaojing in the name of Daji， and it is the correct name of the herbal medicine in all dynasties， there are also other aliases such as Qiongju， Hongya Daji， and Xiamaxian. The dried roots of Euphorbia pekinensis from Euphorbiaceae was the mainstream of the past dynasties. Before the Ming dynasty， the above ground parts of E. pekinensis were used as Zeqi in herbal works. However， since LI Shizhen in the Ming dynasty proposed that the origin of Zeqi should be E. helioscopia， the aerial part of EPR is no longer used as medicine. Since modern times， the roots of Knoxia valerianoides has been used as EPR， and has become the mainstream of commodities， which should be corrected. Throughout history， it has been recorded that the main producing areas were Jiangsu， Anhui， Zhejiang， Shanxi and other regions， while modern botanical survey have shown that EPR is a widespread species distributed throughout the country. In ancient times， the harvesting time of EPR was mostly the twelfth lunar month， while in modern time， it is more common to harvest in autumn and winter. The main processing methods of EPR in ancient times were vinegar processing， wine processing， and stir frying， while in modern times， it is uniformly vinegar processing. In the medicinal properties and clinical aspects， the records are basically consistent throughout history， mainly characterized by bitter taste， cold and toxic nature. Its main efficacy is expelling water retention and reducing swelling. Based on the textual research， it is suggested to choose the dried roots of E. pekinensis when famous classical formulas containing EPR， processing method can be based on the original specified prescription requirements， if the processing method is not clear， it is recommended to use vinegar-processed products as medicine.

Periodontitis and rheumatoid arthritis (RA) are chronic inflammatory diseases that share similar inflammatory mechanisms and characteristics. Programmed cell death (PCD) has recently garnered attention for its crucial role in regulating inflammation and maintaining tissue homeostasis, as well as for its potential to link these two diseases. The various forms of PCD--including apoptosis, pyroptosis, and necroptosis--are closely controlled by signaling pathways such as Toll-like receptor 4 (TLR4) /NF-κB and MAPK. These pathways determine cell fate and influence inflammatory responses, tissue destruction, and repair, and they both play important roles in the pathogenesis of RA and periodontitis. In periodontitis, periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis) and its virulence factors, including lipopolysaccharide (LPS), induce pyroptosis and necroptosis in immune cells such as macrophages via the TLR4/NF-κB pathway, which leads to an excessive release of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Concurrently, these pathogens inhibit the normal apoptotic process of immune cells, such as neutrophils, prolonging their survival, exacerbating immune imbalance, and aggravating periodontal tissue destruction. Similarly, in RA synovial tissue, fibroblast-like synoviocytes (FLS) acquire apoptosis resistance through signaling pathways such as the Bcl-2 family, JAK/STAT, and NF-κB, allowing for the consistent proliferation and secretion of matrix metalloproteinases and pro-inflammatory cytokines. Meanwhile, the continuous activation of pyroptotic pathways in neutrophils and macrophages results in the sustained release of IL-1β, further exacerbating synovial inflammation and bone destruction. Notably, dysregulated PCD fosters inter-organ crosstalk through shared inflammatory mediators and metabolic networks. Damage-associated molecular patterns (DAMPs) and cytokines that originate from periodontal lesions can spread systemically, influencing cell death processes in synovial and immune cells, thereby aggravating joint inflammation and bone erosion. By contrast, systemic inflammation in RA can upregulate osteoclastic activity or interfere with the normal apoptosis of periodontal cells via TNF-α and IL-6, ultimately intensifying periodontal immune imbalance. This review highlights the pivotal bridging role of PCD in the pathogenesis of both periodontitis and RA, providing a reference for therapeutic strategies that target cell death pathways to manage and potentially mitigate these diseases.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

ObjectiveTo investigate the current status of first aid knowledge among middle-aged and elderly residents aged 50 and above in a community in Shanghai， in order to provide reference for improving the self-rescue and mutual aid capabilities of middle-aged and elderly residents. MethodsA multi-stage stratified random sampling method was used to conduct a survey on 335 residents aged 50 and above in a community in Shanghai using a self-made survey questionnaire. The current situation and related factors of emergency knowledge level of residents aged 50 and above in the community were comprehensively analyzed. ResultsFirst aid knowledge level of 335 residents aged 50 and above was low， and the rate of high cognitive level was only 24.18%. Univariate analysis showed that male residents had a higher awareness rate than female residents （P=0.044）， while residents aged 70 and above and 60‒ had lower awareness rates than residents aged 50‒ （P<0.05）. Residents with chronic diseases had a higher awareness rate than those who did not （P=0.031）. Residents with family members suffering from chronic diseases had a higher awareness rate than those without （P<0.001）. Experience of first aid training affected residents’ awareness of first aid （P=0.003）. ConclusionThe level of first aid knowledge among middle-aged and elderly residents aged 50 and above in the community is low. Age， the presence of chronic diseases in family members， and emergency training are independent and relevant factors that affect the awareness of first aid knowledge among middle-aged and elderly residents. The government and relevant institutions should explore the establishment of a standardized emergency response training system， implement classification and grading for middle-aged and elderly groups with different characteristics， and provide targeted emergency training to strengthen their self-rescue and mutual aid capabilities and improve the success rate of pre-hospital emergency care.

ObjectiveTo analyze the suicidal behavior in hospitalized patients with major depression and its influencing factors. MethodsA total of 1 000 patients with major depression admitted to our hospital from January 2017 to July 2021 were selected as the research subjects to investigate the status quo of suicidal behavior of the enrolled patients. According to the survey results， the patients were divided into suicidal behavior group and non-suicidal behavior group， and the related factors affecting their suicidal behavior. ResultsA total of 511 cases （51.10%） of the patients with major depression committed suicide in hospital， including 271 cases （27.10%） of suicidal ideation， 186 cases （18.60%） of attempted suicide， and 54 cases （5.40%） of suicide death. 489 patients （48.90%） did not commit suicide. Univariate analysis showed that there were significant differences in age， gender， marital status， loss of interest or pleasure， anxiety， sense of worthlessness or self-guilt， sleep status， personality， depressive episodes and paranoia between the suicidal behavior group and the non-suicidal behavior group （all P<0.05）. Logistic multifactorial regression analysis showed that age ≤28 years （OR=1.54）， female （OR=1.93）， anxiety （OR=1.61）， sense of worthlessness or self-guilt （OR=1.85） and paranoia （OR=2.15） were all independent predictors of suicidal behavior in the patients with major depression. ConclusionThe incidence of nosocomial suicide in patients with major depression is high. Early onset age， female， anxiety， sense of worthlessness or self-guilt， more depressive episodes and paranoia are independent risk predictors of suicide in patients with major depression. This finding can be used for clinical intervention to reduce the occurrence of suicide in patients.

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

OBJECTIVE To investigate whether the microRNA-222(miRNA-222) carried by plasma exosomes can serve as an early warning marker for cognitive impairment induced by shRNA-PCSK9. METHODS The high-fat diet(HFD) was used to prepare a hypercholesterolemic mouse model group. The model group mice were divided into HFD-shRNA control group and HFD-shRNA-PCSK9 group. The shRNA-PCSK9 was constructed, injected intravenously into the body, and the expression of PCSK9 mRNA was detected by real-time PCR(RT-PCR). Tau protein and phosphorylation in brain tissue were observed by immunohistochemistry (IHC). Western blotting was used to detect Tau protein and P-Tau protein. Serum amyloid Aβ1-42Ab levels were determined by ELISA. The kits extracted plasma exosomes step by step, identify the exosome morphology by negative staining electron microscopy, and determined the size of exosomes by NTA technology. RT-PCR technique was used to detect the expression level of miRNA-222 carried in plasma exosomes. RESULTS The model mouse were prepared by feeding HFD for 13 weeks, whose total cholesterol(TC) and low-density lipoprotein(LDL-C) contents in serum were significantly increased. At the same time, the expression of PCSK9 mRNA in the brain tissue of model group was significantly increased. After shRNA-PCSK9 lentivirus interference, PCSK9 mRNA expression was inhibited, and IHC observed that shRNA-PCSK9 induced abnormal expression and hyperphosphorylation of Tau protein in brain tissue, indicating that the pathological changes of neurofibrillary tangles had occurred. However, at this time, serum Aβ1-42Ab had not been significantly increased, and it had not yet been of significance for the diagnosis of cognitive impairment. The miRNA in plasma exosomes was extracted, and RT-PCR results showed that the expression of miRNA-222 carried in the exosomes of the HFD-shRNA-PCSK9 group was significantly lower than that of the HFD-shRNA control group. CONCLUSION Plasma exosomes carried miRNA-222 provides an early warning marker for shRNA-PCSK9- induced cognitive impairment.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

AIM: To investigate the clinical efficacy and safety of XEN drainage tube implantation combined with mitomycin C(MMC)for open angle glaucoma(OAG).METHODS:A total of 37 OAG patients(37 eyes)were retrospectively included, grouped by anti-glaucoma surgical treatment as the first choice or not, with 17 patients(17 eyes)in the group with primary surgical treatment, and 20 patients(20 eyes)in the group with the numerous surgeries. The intraocular pressure(IOP), kinds of IOP-lowering drugs, and complications were collected and analyzed in 1 a follow-up postoperatively.RESULTS:Upon the one-year follow-up, IOP had decreased from 27.56±9.94, 28.43±14.18 mmHg to 15.16±3.65, 17.18±5.83 mmHg in both groups, respectively, representing a reduction of 55.01% and 60.43%, respectively(t=4.863, P<0.001; t=3.255, P=0.004). The IOP at various follow up points were lower than preoperative points in both groups(Ftime=6.876, Ptime<0.001; Fintergroup=0.242, Pintergroup=0.626; Ftime×intergroup=0.959, Ptime×intergroup=0.458). The complete success rate was 47% and 45%, the qualified success rate was 76% and 75%(Z=-0.115, P=0.909), respectively, and there was no significant difference in the cumulative survival rate between two groups(χ2=0.042, P=0.838; χ2=0.004, P=0.949). At the last follow up, IOP-lowering drugs were reduced from 3(2, 3)to 1(0, 2)in both groups(Z=-3.289, -3.796, all P<0.001), and no significant difference between groups(Z=-0.581, P=0.561). Hypotony is the most common short-term complications, anterior chamber haemorrhage followed, while, filtering bleb encapsulation is the most frequent long-term complication, no serious complications occurred, but with XEN drainage tube exposure in 1 eye and drop in 1 eye.CONCLUSION:Initial XEN drainage tube implantation combined with MMC and numerous glaucoma surgeries are both safe and effective treatment for OAG patients, while the incidence of filtering bleb encapsulation is high in those with numerous glaucoma surgeries.