OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

OBJECTIVE To establish a interview outline design process and quality control evaluation method based on grounded theory， providing ideas for qualitative research interview outline design in medical fields. METHODS A literature review was conducted to understand the current research status； a preliminary interview outline was developed around the research content. The triangulation method， group evaluation， expert review and pre-interview were adopted to execute the interview outline and conduct quality control. The evaluation indicators and target values were formulated （an average score for the overall quality evaluation of all indicators ≥4.5， and an average score for individual indicators ≥4.00） to evaluate the effect of the interview outline. Taking the research on the mechanism of physicians’ prescribing behavior under the background of Diagnosis Related Groups （DRGs） payment as an example， the methodological contents of above interview outline were applied in practical research. RESULTS The interview outline included basic information and interview questions. The interview questions were divided into three parts：influencing factors survey， promoting and hindering factors of standardizing physician prescription behavior， and communication， with a total of 12 questions. After being reviewed by members of the research group， experts review and pre- interview， a total of 9 people participated in the quality control evaluation of the interview outline. The overall evaluation score was 4.94 （＞4.50）， and the average score of each indicator was greater than 4.00， indicating that the quality of the outline met the requirements for the interview and could be used for the formal interview. CONCLUSIONS The established interview outline design and quality control method based on grounded theory provides ideas for the qualitative research interview outline design in the medical field， and lays the foundation for further using grounded theory to study the influencing factors and mechanisms of physician prescription behavior under the DRG background.

Objective: To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis. Methods: Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting. Results: There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05). Conclusion The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.

This paper summarizes Professor ZHAI Shuangqing's clinical experience in using metal and mineral medicines to treat mental disorders. Based on xiang thinking， the symptoms of mental disorders are classified into five categories， depression-xiang， wind-xiang， fire-xiang， phlegm-xiang， and deficiency-xiang， and the mechanisms of disease development are discussed accordingly. Metal and mineral medicines are key treatments for mental disorders， not only having the function of calming the mind but also promoting qi， stabilizing wind， expelling evil， and tonifying. In clinical practice， the emphasis is placed on harmonizing the disease and its symptoms. Based on self-developed prescription formulas， the appropriate metal and mineral medicines are selected according to the properties， flavors， meridian tropism， and actions of the medicines， as well as the xiang patterns of the mental disorder. For example， Attention Deficit Hyperactivity Disorder （ADHD） is treated by Modified Xiehuang Powder （泻黄散） with Sijunzi Decoction （四君子汤） and adding Fulonggan （Testudinis Carapax） and Longgu （Os Draconis）. Persistent insomnia is treated by combining a self-developed insomnia formula with Longgu （Os Draconis）， Hupo （Succinum）， and Cishi （Magnetitum）. Obsessive-compulsive disorder （OCD） is treated by combining a self-developed OCD formula with Longchi （Dens Draconis）， Qingmengshi （Fluoritum）， and Zheshi （Haematitum）. Epilepsy is treated by combining an anti-epilepsy decoction with Qingmengshi （Fluoritum）， Longchi （Dens Draconis）， and Shengtieluo （Ferrum Rudis）.

A wealth of prior studies has confirmed that intratumoral microbiota can survive within tumor tissue, thereby promoting or inhibiting tumor growth. With the development of high-throughput sequencing and metabolomics, increasing attention has been paid to the correlation between intratumoral microbiota and host metabolism, and their effect on tumorigenesis and progression. This review focuses on the interaction between intratumoral microbiota and tumor metabolism. It emphasizes the effects of intratumoral microbiota on tumor sugar, lipid, and amino acid metabolism and explores emerging therapeutic strategies for guiding tumor prevention and treatment by modulating tumor metabolism. Although the specific role of intratumoral microbiota in tumor metabolism remains to be further studied, a deepened understanding of the interaction between tumor-specific microbiota and tumor metabolism may provide new directions and application prospects for tumor prevention and treatment.

Objective To explore the potential causality between visceral adipose tissue (VAT) and inflammatory bowel disease, peptic ulcer disease, irritable bowel syndrome and gastroesophageal reflux disease. Methods Two-sample Mendelian randomization (MR) investigations were carried out, employing genetic variants closely linked with VAT as instrumental variables. The summary data for aforementioned gastrointestinal disorders were obtained from the genome-wide association study (GWAS) in UK biobank and Finn Gen databases, respectively. The inverse variance-weighted method (IVW) was employed as the primary analytical method, bolstered by a sequence of sensitivity analyses to verify the robustness of MR. Subsequently, a meta-analysis was conducted to amalgamate the findings derived from both databases. Results This study included a total of 42 single nucleotide polymorphisms that were strongly associated with visceral adipose tissue as instrumental variables. Statistically significant correlations were found between VAT and peptic ulcer (OR=1.17, 95% CI: 1.08-1.27, P < 0.01), gastroesophageal reflux disease (OR=1.10, 95% CI: 1.03-1.18, P = 0.02), and irritable bowel syndrome (OR=1.12, 95% CI: 1.04-1.12, P = 0.03). There was no statistical significance between VAT and inflammatory bowel disease (OR=0.94, 95% CI: 0.79-1.12, P = 0.65). Conclusion VAT exhibits a causal linkage with peptic ulcer, gastroesophageal reflux disease, and irritable bowel syndrome. Accurately assessing VAT levels via imaging methods, screening individuals at high-risk, and actively controlling abdominal obesity bear important clinical significance.

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Objective:To analyze and compare the pathological data characteristics of patients with simple papillary thyroid carcinoma (PTC) and PTC combined with Hashimoto’s thyroiditis (HT), so as to provide clinical treatment ideas.Methods:A retrospective analysis was performed on the medical records of 326 PTC patients who met the requirements and underwent surgical treatment in the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine from Jan. 2020 to May. 2022. There were 81 males and 245 females. They were divided into PTC group and HT-PTC group, according to whether they were combined with HT. Clinical data were collected and organized. The collection indicators included patient gender, age, body mass index (BMI), five preoperative thyroid function items including free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), BRAF gene mutation, single or bilateral lesions, single or multiple lesions, largest postoperative pathological tumor lesions diameter, cervical lymph node metastasis (LNM) status, etc. At the same time, all patients were divided into CLNM group and no CLNM group according to CLNM status. The two groups were compared in terms of gender, age ≥55 years old, whether combined with HT, number of lesions, unilateral and bilateral, extraglandular invasion, microcarcinoma, and BRAF gene. Statistical software was used to analyze the results. t test, χ2 test, and logistic regression analysis were adopted. P<0.05 indicates that the difference is statistically significant. Results:The proportion of female patients in both groups was higher, and the proportion of female patients in the HT-PTC group (90/100, 90%) was higher than that in the PTC group (155/226, 69.59%). HT-PTC patients were younger than patients in the PTC group (43.03±12.72 vs. 43.70±12.63) years old, and their TSH (2.71±1.69 vs. 2.02±1.46) uIU/mL was higher. The differences were statistically significant (all P<0.05). There were no statistically significant differences in BMI, FT3, FT4, T3, or T4 (all P>0.05). The HT-PTC group had a lower proportion of BRAF gene mutations [87/100 (87%) vs. 212/226 (93.8%) ], a smaller maximum tumor diameter (1.06±0.73 vs. 1.32±0.97 cm), and a lower proportion of CLNM [37 /100 (37%) vs. 118/226 (52.2%) ]. The number of LNMs with metastasis is less (3.33±2.21 vs. 4.76±4.00), and it was more likely to be multifocal [44/100 (44%) vs. 73/226 (32.74%) ]. All differences were statistically significant (all P<0.05), and the differences in bilateral gland lobes involvement and extra-glandular invasion were not statistically significant. When accompanied by CLNM, gender (male vs. female) [55/100 (35.45%/64.52%) vs. 26/145 (15.2%/84.85%) ], age ≥ 55 years (yes vs. no) [21/134 (13.55) %/86.45%) vs. 50/121 (29.24%/70.76%) ], HT (yes vs. no) [37/118 (23.87%/76.13%) vs. 63/108 (36.84%/63.16%), number of lesions (single focus vs. multiple focus) [90/65 (41.94%/50.06%) vs. 119/52 (69.59%/30.41%) ], microcarcinoma (yes vs. no) [83/72 (53.55%/45.45%) vs. 139/32 (81.29%/18.71%) ] and extraglandular invasion (with vs. without) [38/117 (24.52%/75.48%) vs. 27/144 (17.42%/84.21%) ] had statistics significance (both P<0.05). There was no statistical significance in bilateral lesion involvement or BRAF gene mutation (all P>0.05). Multivariate logistic regression analysis showed that age, microcarcinoma, HT, gender, and number of lesions were independent risk factors for CLNM, and male gender and multifocal cancer were risk factors for CLNM. Age ≥55 years, microcarcinoma, and combined HT were negatively associated with CLNM. Conclusions:HT may promote the occurrence of PTC, but can inhibit its development. In the short term, patients with HT can have a better prognosis than those with simple PTC.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques