OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To compare the efficacy and safety of video-assisted thoracoscopic surgery (VATS) thymectomy for the treatment of thymoma through subxiphoid uniportal approach using double sternum retractors, and subxiphoid and subcostal arch approach. Methods We retrospectively analyzed the clinical data of the patients diagnosed with thymoma who underwent VATS thymectomy from June 2023 to June 2024 in West China Hospital. Patients were categorized based on the surgical approach into two groups: a subxiphoid uniportal VATS thymectomy (SUVT) group and a subxiphoid and subcostal arch VATS thymectomy (SASAT) group. Comparisons were made between the two groups regarding surgical duration, intraoperative blood loss, postoperative drainage, thymoma size and location, and postoperative pain assessed using the visual analogue scale (VAS). Results The SUVT group consisted of 20 patients, including 11 males and 9 females, with an average age of (51.5±14.3) years. The SASAT group comprised 40 patients, including 26 males and 14 females, with an average age of (50.0±13.0) years. Compared to the SASAT group, the SUVT group had significantly larger thymomas [ (5.9±2.7) cm vs. (4.2±2.1) cm, P=0.010] and a higher proportion of neoplasms located in the superior mediastinum (30.0% vs. 2.5%, P=0.007). Additionally, the VAS pain scores on postoperative days 3, 7, and 30 were significantly lower in the SUVT group compared to the SASAT group (P<0.05). There were no statistical differences between the two groups in demographic characteristics, operative time, intraoperative blood loss, duration and volume of postoperative drainage, length of postoperative hospital stay, or the VAS pain score on the first postoperative day. Conclusion SUVT using double sternum retractors significantly reduces postoperative pain and provides superior efficacy in the resection of larger thymomas or those situated in the superior mediastinum.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

This study aims to establish a method for counting the viral particles in adenovirus vector-based vaccines. Nano-flow cytometry was employed to analyze the viral particles in adenovirus-based vector vaccines at the single-particle level. Monodisperse silica nanoparticles with a refractive index close to that of the virus were selected as the particle size standard to calculate the viral particle size, which was then compared with the results obtained from transmission electron microscopy (TEM) to determine the gating strategy. Subsequently, a particle count standard was employed to calculate the viral particle concentration. The established method demonstrated good linearity, accuracy, precision, and specificity. The results of determined viral particle concentration showed a good correlation with the infectious titer. Compared with the conventional OD₂₆₀ method, nano-flow cytometry can directly measure the viral particle concentration and indicate whether the sample has been disassembled according to changes in viral particle concentration and size, thus more accurately reflecting the actual infectious potency of the sample. The novel quantification method established in this study is capable of indicating the efficacy of adenovirus vector-based vaccines and provides effective technical support for the quality control of such products.
Adenoviridae/genetics* ; Genetic Vectors ; Flow Cytometry/methods* ; Virion/isolation & purification* ; Particle Size ; Nanoparticles ; Viral Vaccines

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Objective:To investigate the prognostic value of serum chloride ion concentration in critically ill or clinically stable pa-tients with decompensated cirrhosis.Methods:A retrospective study was conducted among the patients with decompensated cirrhosis who attended the intensive care unit(ICU)and Department of Gastroenterology,The First Hospital of Lanzhou University,from Janu-ary 2017 to January 2022,and the patients were divided into ICU cohort and Gastroenterology cohort.The outcome event for the ICU cohort was in-hospital death.A logistic regression analysis was used to investigate the association between serum chloride levels and ICU mortality rate;the receiver operating characteristic(ROC)curve was plotted and the area under the ROC curve(AUC)was calcu-lated to assess the value of blood chloride level in predicting ICU mortality rate.The patients in the Gastroenterology cohort were fol-lowed up with the outcome event of all-cause mortality rate,and the Cox regression analysis and the Kaplan-Meier analysis were used to investigate the value of blood chloride level in predicting mortality rate.Results:In the ICU cohort,serum chloride ion was signifi-cantly associated with in-hospital mortality in the ICU(odds ratio=0.934,95%CI=0.871-0.993,P=0.035),and blood chlorine had an AUC of 0.687 in predicting in-hospital mortality in the ICU.In the Gastroenterology cohort,serum chloride ion concentration was sig-nificantly associated with mortality rate in the subgroup with a Child-Pugh score of<10(hazard ratio=0.906,95%CI=0.822-0.997,P=0.043),and hypochloremia was associated with a lower survival rate.Conclusion:Hypochloremia is associated with the increase in mortality rate in patients with decompensated cirrhosis.

Background:Postoperative nutritional status and nutritional support therapy are important driving factor for clinical outcomes in patients after lung transplantation.This study aims to evaluate the relationship between mNUTRIC scores and prognosis in patients after lung transplantation.Methods:A retrospective inclusion of 253 patients who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2020 to December 2022.The nutritional risk in patients after lung transplantation is much higher than in other critically ill patients.To explore the optimal threshold,patients were divided into three groups based on the tertiles of mNUTRIC scores,and clinical outcomes were compared.The predictive ability of the mNUTRIC score was analyzed using receiver operating characteristic(ROC)curve.The appropriate threshold was determined using the Youden index based on the highest combined sensitivity and specificity.Results:Among 253 patients,the 30-day mortality rate was 14.2%.The death group had higher age and BMI,with APACHE II,SOFA,and mNUTRIC scores all higher than those in the survival group.The median mNUTRIC score in the death group was 5.00(3.00～6.00).The higher the mNUTRIC score,the greater the gradual increase in 30-day mortality rate.When the mNUTRIC score was 4～6,the patient mortality rate was 21.21%,and when 7～9,it was 42.31%.The Q3 group had significantly prolonged mechanical ventilation time,was more prone to delayed weaning,had longer ICU length of stay,and higher tracheotomy rate.Multivariate Cox regression analysis and Kaplan-Meier survival curve showed that mNUTRIC score is an independent risk factor for 30-day mortality,with mortality rate increasing as the score increased(P<0.001).The area under the ROC curve(AUC)for mNUTRIC score was 0.765(95%CI:0.686,0.644).According to the Youden index,the optimal cutoff value is when mNUTRIC score equals 3.5,used to predict high nutritional risk and 30-day mortality in lung transplant patients.Conclusion:The mNUTRIC score has a good predictive effect on the prognosis of patients after lung transplantation and is expected to be applied in clinical practice as a routine assessment tool to help clinicians perform postoperative nutritional risk stratification.