ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective:To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia(ChP)2025 Edition,and explore its novel requirements in risk-based pharmaceutical product lifecycle management.Methods:A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview,international harmonization of microbiological standards,risk-based quality man-agement system,and novel tools and methods with Chinese characteristics.Results:The ChP 2025 edition demon-strates three prominent features in microbiological-related standards:enhanced international harmonization,intro-duced emerging molecular biological technologies,and established a risk-based microbiological quality control sys-tem.Conclusion:The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system,which significantly improves the scientificity,standardization and applicability of the standards,providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective:To investigate the impact of coronary angiography-derived index of microcirculatory resistance (caIMR) on the long-term prognosis of patients with coronary heart disease (CHD) undergoing elective percutaneous coronary intervention (PCI).Methods:The study was a retrospective cohort study conducted at a single centre. Patients who successfully underwent elective PCI with pre-and post-PCI caIMR measurements in Peking University First Hospital between August 2013 and December 2020 were included. Then patients were categorised into three groups based on pre-and post-PCI caIMR: post-PCI caIMR<25 U group, pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group, and both pre-and post-PCI caIMR≥25 U group. Collected clinical data of patients, including comorbid diabetes mellitus.The primary endpoint was a composite endpoint, defined as a composite of all-cause death, non-fatal myocardial infarction, and any revascularisation. The association between caIMR-based groupings and clinical outcomes was analysed using Cox proportional hazards regression models.Results:A total of 625 patients who underwent successful elective PCI were included in the study, among whom 294 (47.0%) had stable angina. The age was (64.5±10.1) years, and 440 (70.4%) patients were male. Over a median follow-up of 3.69 (1.80, 5.80) years, 122 patients (19.5%) experienced composite endpoint events. Post-PCI caIMR≥25 U in combination with diabetes mellitus was associated with an increased risk of the composite endpoint compared to those with post-PCI caIMR<25 U and without diabetes mellitus (adjusted HR=2.13, 95% CI 1.17-3.88, P=0.014). In the combined analysis, compared with post-PCI caIMR<25 U group, those with both pre-and post-PCI caIMR≥25 U had higher risks of composite endpoint (adjusted HR=2.01, 95% CI 1.18-3.43, P=0.010) and any revascularisation (adjusted HR=2.12, 95% CI 1.17-3.84, P=0.013). The pre-PCI caIMR<25 U and post-PCI caIMR≥25 U group showed no statistically significant differences in any of the endpoints compared to post-PCI caIMR<25 U group. Conclusions:Integrated pre-and post-procedural assessment of caIMR may enhance risk stratification in patients with coronary heart disease. Persistent coronary microvascular dysfunction present both before and after PCI, as measured by caIMR, serves as an independent risk factor for adverse events in patients with coronary heart disease undergoing elective PCI.

This article reports the diagnosis and treatment of two cases of complex ureteral obstruction (UO) in transplanted kidneys managed at Tangdu Hospital of Air Force Medical University of PLA in 2023. UO is a challenging complication following kidney transplantation, with surgical repair being the primary treatment approach. Both patients underwent robot-assisted laparoscopic (RAL) anastomosis of the transplanted kidney collecting system with the autologous ureter. The procedures were successfully performed, and both recipients were discharged without complications. During a six-month postoperative follow-up, the morphology and function of the transplanted kidneys remained stable, with no recurrence of hydronephrosis, fever, pain, urinary frequency, or urgency. This case report provides new insights into the diagnosis and surgical management of complex UO in kidney transplant recipients.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

Objective:To investigate the effect of GBP3 on replication of adult T-lymphocytic leukemia virus type 1(HTLV-1).Methods:Expression of GBP3 in HTLV-1-infected HeLa cell and THP1 cell was detected by Western blot.The knock-down efficiency of siRNAs targeting GBP3 in HeLa and THP1 cells was evaluated by Western blot.Effects of GBP3 overexpression or knockdown on expression of HTLV-1 proviral transcripts Tax,px,HBZ,Gag,ENV,5'UTR,and viral proteins Tax,p19 were investigated by RT-qPCR and Western blot.GTPase-defective mutant of GBP3,GBP3K51A was constructed to explore whether the effects of GBP3 on HTLV-1 infection were dependent on its GTPase activity.Results:GBP3 expression was upregulated in HTLV-1 infected HeLa and THP1 cells.GBP3 overexpression decreased expression of HTLV-1 proviral transcripts and viral proteins,whereas the knockdown of GBP3 has the opposite effects.Overexpression of GBP3K51A increased expression of HTLV-1 proviral transcripts and viral proteins.Conclusion:HTLV-1 virus infection can induce expression of GBP3;overexpression of GBP3 inhibits virus replication and may depend on GTPase.

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.