Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A （H1N1） virus infection based on the gut-lung axis. MethodsBALB/c mice were randomly assigned into a blank control group， a model control group， a positive control （oseltamivir phosphate capsules， 19.5 mg·kg^-1） group， and a Huashi Baidu granules （17.81 g·kg^-1） group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated， and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific proteinase -1 （Caspase-1）， apoptosis-associated Speck-like protein containing a CARD （ASC）， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β， and colonic tight junction protein 1 （CLDN1）， and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the 5-hydroxytryptamine （5-HT） levels in the serum， lung tissue， and colon tissue. ResultsCompared with the blank control group， the model control group showed elevated lung index， marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue， obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue， upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in the lung and colon tissue （P<0.05， P<0.01）， downregulated protein levels of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Compared with the model control group， Huashi Baidu Granules reduced the lung index （P<0.01）， alleviated pathological damage in the lungs and colon， inhibited the expression of NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in lung and colon tissue （P<0.05， P<0.01）， and upregulated the expression of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue， while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group， the model control group exhibited elevated levels of 5-HT in the serum， lung tissue， and colon tissue （P<0.01）. The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum （P<0.05） and the lung and colon tissue （P<0.01）. Huashi Baidu Granules increased the diversity of gut microbiota， enriched beneficial bacteria such as Blautia， and inhibited pathogenic bacteria such as Desulfovibrio. ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A （H1N1） virus， reshape the intestinal microecology， and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.

Objective:To retrieve and integrate the best evidence on foot offloading management for diabetic high-risk foot patients, and to provide evidence-based basis for effectively preventing the occurrence and development of diabetic foot ulcers.Methods:Clinical practice guidelines, evidence summaries, systematic reviews and expert consensus on the management of foot offloading at high risk of diabetes were searched in Chinese and English databases, domestic and foreign diabetes association websites, clinical decision websites and guideline websites, retrieval time for libraries to March 31, 2024, respectively, by the 2 researchers quality evaluation, evidence extraction, the final summary.Results:A total of 16 articles were included, including 6 guidesline, 5 expert consensuses, 1 evidence summary and 4 systematic reviews. According to the existing evidence, the best evidence of foot offloading management in patients with diabetic high-risk foot was summarized from 6 aspects: evaluation, monitoring, referral, offloading brace, exercise advice and risk factor intervention, 14 subcategories, 32 best evidences for foot offloading management in patients with high-risk diabetic foot.Conclusions:This study summarized the best evidence for foot offloading management in patients with high-risk of diabetic foot, which is convenient for the further development of clinical practice of foot offloading management in patients with high-risk of diabetes, and provides evidence-based basis for clinical medical staff to expand related research.

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 investigate the effect of long non-coding RNA non-coding RNA-activated by DNA damage(LncRNA NORAD)on macrophage apoptosis induced by Mycobacterium tuberculosis infection via sponging microRNA-20a-5p(miR-20a-5p).Methods Healthy subjects(n=50)who came for health checkup,patients with active tuberculosis(n=50)and individuals with asymptomatic M.tuberculosis infection(n=50)were enrolled from Hebei Chest Hospital from March 2022 to April 2023.Venous blood samples were collected to prepare serum samples.The expression levels of LncRNA NORAD,miR-20a-5p,and inflammatory factors in the serum were measured.Human monocyte line THP-1 was induced to differentiate into macrophages and assigned into Control group,Model group,transfection of NORAD empty vector group(sh-NC group),transfection of sh-NORAD vector group(sh-NORAD group),co-transfection of sh-NORAD and miR-20a-5p inhibitor empty vector group(sh-NORAD+miR-20a-5p inhibitor NC group),co-transfection of sh-NORAD and miR-20a-5p inhibitor vector group(sh-NORAD+miR-20a-5p inhibitor group),transfection of miR-20a-5p empty vector group(miR-NC group),and transfection of miR-20a-5p vector group(miR-20a-5p mimics group).The expression levels of LncRNA NORAD and miR-20a-5p(qRT PCR method),cell proliferation ability(CCK-8 kit method),cell apoptosis(flow cytometry method),inflammatory factor levels(ELISA method),and protein expression levels of BCL2-Associated X(Bax),B-cell lymphoma-2(Bcl-2),and cleaved caspase 3 in cells were detected.The targeted relationship between LncRNA NORAD and miR-20a-5p was validated.Results Compared with healthy subjects,the patients with active tuberculosis and asymptomatic M.tuberculosis infection had significantly higher serum levels of inflammatory factors and expression of LncRNA NORAD,and significantly lower miR-20a-5p.Compared with Control group,Model group had significantly higher LncRNA NORAD level,cell proliferation ability,Bcl-2 protein expression,and inflammatory factor levels,but significantly lower miR-20a-5p level,apoptosis rate,and Bax and cleaved caspase 3 protein expression(P＜0.05).Compared with the sh-NC group,the sh-NORAD group had significantly lower LncRNA NORAD level,Bcl-2 protein expression,inflammatory factor levels,and cell proliferation ability,but significantly higher miR-20a-5p level,apoptosis rate,and Bax and cleaved caspase 3 protein expression(P＜0.05).Compared with the sh-NORAD+miR-20a-5p inhibitor NC group,the sh-NORAD+miR-20a-5p inhibitor group had significantly higher inflammatory factor levels,Bcl-2 protein expression,and cell proliferation ability,but significantly lower miR-20a-5p level,apoptosis rate,and Bax and cleaved caspase 3 protein expression(P＜0.05).Compared with the miR-NC group,the miR-20a-5p mimics group had significantly increased inflammatory cytokines and proliferation ability,and significantly reduced apoptosis rate(P＜0.05).The targeted relationship between LncRNA NORAD and miR-20a-5p was further confirmed through experiments.Conclusions LncRNA NORAD is overexpressed in macrophages induced by M.tuberculosis.Silencing the expression of LncRNA NORAD can target the downregulation of miR-20a-5p expression,thereby inhibiting the inflammatory response of macrophages induced by M.tuberculosis and promoting cell apoptosis.

Objective:To compare the efficacy and safety of irradiation-incorporated and chemotherapy only-based myeloablative conditioning regimens in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for patients with high-risk myeloid malignancies.Methods:This study retrospectively collected clinical data from 63 high-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients who underwent haplo-HSCT at the Fifth Medical Center of the Chinese PLA General Hospital from January 2015 to December 2019. These patients were classified into the irradiation ( n = 17) and chemotherapy ( n = 46) groups based on different conditioning regimens. The differences between the two groups were compared in terms of hematopoietic reconstitution, cumulative incidence of acute/chronic graft-versus-host diseases (aGVHD and cGVHD), non-relapse mortality (NRM), relapse rate (RR), overall survival (OS), and disease-free survival (DFS), followed by the analysis of prognostic factors. Results:The median follow-up time for the irradiation and chemotherapy groups was 78.5 and 72.3 months, respectively. The median time for neutrophil engraftment was 14.0 days in the irradiation group and 14.5 d in the chemotherapy group, and for platelet engraftment was 15.0 and 13.0 d, respectively. As a result, the two groups showed no statistically significant differences in hematopoietic reconstitution ( P > 0.05). The cumulative incidence of aGVHD and cGVHD was higher in the irradiation group compared to the chemotherapy group, yet showing no statistically significant differences ( P > 0.05). Specifically, the cumulative incidence of grade Ⅱ-Ⅳ aGVHD within 100 d was 29.4% and 21.7% for the irradiation and chemotherapy groups, respectively. The cumulative incidence of grade Ⅲ-Ⅳ aGVHD was 23.5% and 13.0%, respectively. The cumulative incidence of severe cGVHD within five years was 11.8% in the irradiation group and 8.7% in the chemotherapy group. In terms of long-term survival, the cumulative 5\|year RR and NRM were 20.2% and 28.4% in the irradiation group, 5.9% and 23.9% in the chemotherapy group, respectively, showing no statistically significant differences ( P > 0.05). The 5-year DFS and OS rates were 73.9% and 47.7% in the irradiation group, and 81.1% and 54.4% in the chemotherapy group, respectively, without statistically significant differences ( P > 0.05). Notably, the irradiation group manifested more favorable DFS and OS survival curves compared to the chemotherapy group. The survival curves indicate that the irradiation-incorporated regimen exhibited better trends in OS, DFS, and cGVHD-free relapse-free survival (GRFS). However, multivariate analysis did not reveal that irradiation conditioning is an independent prognostic factor affecting survival [ HR = 0.532 (0.163-1.735), 0.370 (0.091-1.516), 0.683 (0.248-1.882), P > 0.05]. Conclusions:In haplo-HSCT for high-risk myeloid malignancies, the irradiation-incorporated conditioning regimen demonstrates lower RR and NRM, higher DFS and OS, and potentially superior survival outcomes compared to the chemotherapy only-based regimen. Therefore, the irradiation-incorporated conditioning regimen may be preferentially considered in haplo-HSCT.

Objective To analyze the current situation of quality control and regulation of centralized decoction of Chinese materia medica in Hangzhou through a mixed study combining quantitative research and qualitative research;To provide references for its standardization.Methods A self-designed questionnaire was distributed from July 20,2023 to August 10,2023 in institutions providing centralized decoction services of Chinese materia medica in different regions of Hangzhou.Using the stratified sampling method,the institutional personnel who completed the questionnaire survey were selected as the interviewees,and the semi-structured interview was used to refine the theme according to the Colaizzi seven step method.Results Totally 98 questionnaires were distributed and 96 valid questionnaires were recovered,with a valid recovery rate of 97.96%.There were significant differences in soaking time,concentration degree,and special decoction method such as decocted earlier or later of decoction pieces of Chinese materia medica among different types of institutions(P<0.05).The centralized decoction of Chinese materia medica in Hangzhou mainly involves two themes and seven sub themes:the supervision and management of the whole process of centralized decoction of Chinese materia medica(optimizing distribution of medical resources,strengthening of supervision,demanding guidance of standards),the operation of centralized decoction of Chinese materia medica(soaking time of decoction pieces of Chinese materia medica,the pretreatment operation of"decocted earlier and decocted later",the concentration treatment of Chinese materia medica decoction,and the quality control of Chinese materia medica decoction).Conclusion At present,centralized decoction of Chinese materia medica in Hangzhou still needs to be further standardized.It is recommended to strengthen the construction of shared Chinese materia medica pharmacy in the region,establish and improve the standard system of centralized decoction of Chinese materia medica decoction,and strengthen the construction of digital full chain traceability to improve the service quality and management level of centralized decoction of Chinese materia medica in Hangzhou.

OBJECTIVE To investigate the use of drugs and the development of pharmaceutical care in the tight medical alliance (shorted for "medical alliance") of Wanzhou District of Chongqing,and provide reference for the further construction of the medical alliance.METHODS A survey form was designed and distributed to 21 constituent units (5 leading units and 16 member units) of 5 medical alliances in Wanzhou District of Chongqing.The statistical analysis was conducted in aspects of basic drug allocation and use,pharmaceutical personnel team construction,the development of pharmaceutical care,and rational use of antibiotics.RESULTS Among the 21 constituent units,4 leading units and 14 member units achieved the target for the proportion of essential drug procurement varieties,with a total compliance rate of 85.71％;4 leading units and 13 member units achieved the target for the proportion of national essential drug allocation and usage amount,with a total compliance rate of 80.95％.The proportions of personnel with doctoral degrees in the 5 leading units and 16 member units were 1.71％ and 0 respectively,and the proportions of personnel with senior professional titles were 8.56％ and 1.63％,respectively.A total of 5 pharmacy or pharmaceutical combined outpatient clinics were set up in the 21 medical alliance units,and 5 clinical pharmacy information service platforms were established;all 5 leading units were able to regularly carry out clinical pharmacy projects,while only 4 out of 16 member units had conducted medical order review and evaluation.The proportions of irrational use of antibiotics in outpatient prescriptions and inpatient medical records of the 16 member units (4.81％,5.21％) were significantly higher than those of the 5 leading units (2.80％,4.00％).CONCLUSIONS The allocation and usage of national essential drugs in 21 constituent units from Wanzhou District of Chongqing are both in good standing.However,the data on the allocation of pharmaceutical professionals and the number,qualifications,and job titles of clinical pharmacists in member units are generally low.Moreover,the pharmaceutical service projects and service quality in member units need to be further improved.

Objective:To evaluate the efficacy and safety of the CLAE (cladribine + cytarabine + etoposide) regimen in refractory/relapsed T cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) .Methods:Patients with R/R T-ALL/LBL received the CLAE regimen in a prospective, multicenter, single-arm clinical study or compassionate use. From March 2019 to August 2024, data from 25 patients (18 in the study across five centers and 7 receiving compassionate treatment in Peking University Third Hospital) were collected. Outcomes included objective response rate, complete response (CR) rate, partial response (PR) rate after 1–2 cycles, bridging to allo-HSCT, progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects.Results:Median age was 29 years (range, 13–63) ; 17 were male. Among the 24 evaluable patients, CR rate was 33.3% overall and 41.2% among enrolled patients. Median OS and PFS time were 199 (46–1 310) and 49 (28–1 310) days, respectively. Cumulative OS rate at 6 months, 1 year, and 2 years was (52.1±10.2) %, (29.7±9.3) %, and (27.1±9.1) %, respectively; cumulative PFS rate was (32.6±9.6) %, (24.9±8.9) %, and (23.8±8.7) %, respectively. Among patients achieving CR or PR (8 cases), median OS and PFS were not reached. Cumulative OS rate at 6 months, 1 year, and 2 years was (86.8±12.0) %, (78.3±14.6) %, and (72.9±15.7) %, respectively, and the cumulative PFS rate was (86.4±12.1) %, (74.8±15.3) %, and (72.9±15.7) %, respectively. Adverse events were mainly hematologic; no treatment-related mortality occurred. Seven patients achieving CR were bridged to allo-HSCT, with 5 remaining in continuous remission.Conclusion:The CLAE regimen is safe and effective for R/R T-ALL/LBL, facilitating CR as a bridge to allo-HSCT and potentially improving patient prognosis.

Objective:To summarize the evidence for the application and management of continuous glucose monitoring, providing evidence-based support for the clinical application and management.Methods:BMJ Best Clinical Practice, UpToDate, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang and other databases, Yimaitong and and other guide networks, and diabetes related association websites were searched for the application and management of continuous glucose monitoring, the search time limit was from the establishment of the database to July 7, 2024. Researchers evaluated the quality of the included literature, extracted and summarized the evidence based on the topic.Results:A total of 13 articles were included, including 5 guidelines, 5 expert consensuses, 1 systematic review and 2 randomized controlled trials. The best evidences for the application and management of continuous glucose monitoring were summarized, including 3 themes and 13 aspects, practice norms (before, during, and after wearing), application norms, management norms (personnel, systems, information, materials, methods), with 31 pieces of evidence.Conclusions:This study summarized the evidences for the application management of continuous glucose monitoring, which could standardize the operation process of continuous glucose monitoring, provide response strategies for related nursing issues, and ensure that there were unified and clear management standards to follow.