Diabetes mellitus, characterized by glucose metabolism disorders and marked by insulin deficiency or insulin resistance, has seen a continuous rise in prevalence. In recent years, islet transplantation has matured as a therapeutic approach for diabetes, becoming an important method for glycemic control and the reduction of diabetes-related complications. Donor selection directly influences transplant outcomes, and various research institutions worldwide have proposed multiple scoring systems to optimize donor assessment, such as the University of Alberta scoring system and the North American Islet Donor Score. This article explores the impact of key factors such as donor age, body mass index and ischemia time on islet transplantation. Combining practical experience in pancreatic donor selection from Shanghai Changzheng Hospital, it proposes screening criteria for pancreatic donors suitable for China, aiming to provide new evidence for improving the success rate of islet transplantation.

OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China， and based on the theory of industry-university-research collaborative innovation， the organizational structure， collaborative processes， and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development （R&D） capacity， uneven quality standards， and blocked transformation pathways. This study established a full-chain， whole- industry collaborative innovation network covering the government， medical institutions， universities/research institutes， pharmaceutical enterprises， and the market， forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation， full- chain intellectual property management， contribution-based benefit distribution， staged risk-sharing， and third-party evaluation， the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions， enabling precise alignment between clinical needs and technological R&D， as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction， it effectively achieves optimal resource allocation and complementary advantages， addresses problems emerging in the development of medical institution preparations， and provides reference value for the formulation of relevant systems.

ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective To assess the risk of hearing loss caused by occupational noise exposure in workers in an automobile manufacturing plant in Tianjin, China, and to perform risk management. Methods Occupational health field investigation and noise exposure measurements were conducted from July to December 2023, and physical examination data were collected. ISO 1999:2013(E) Acoustics-Estimation of Noise-Induced Hearing Loss and WS/T 754-2016 ^“Guidelines for Risk Management of Occupational Disease Hazards Caused by Noise^” were used to predict the risk of high-frequency hearing loss and occupational noise induced deafness for operational workers and make a risk classification. Results The noise intensity of each workshop was 79.4 to 95.5 dB(A), and the maximum noise intensity of welding and stamping exceeded the standard. The results of the assessment showed that the noise level remained unchanged, and the risk of HFHL and ONID in workers increased as the predicted age and length of service increased. It was predicted that after the age of 40, the maximum risk of hearing loss in welding workers would be high risk, and the risk of stamping workers would be at higher risk, suggesting that welding and stamping were the key control posts of noise hazards in the enterprise. The N50 prediction values of permanent hearing threshold displacement caused by potential noise at all frequencies for final assembly and painting workers were lower than the measured values. Conclusion The consequences of hearing loss for workers in the welding and stamping shop noise operations at this automobile manufacturing plant are relatively serious and require risk management.

Objective: To explore the therapeutic effects of different surgical methods for temporomandibular joint disc reduction and anchoring surgery, providing reference for optimizing this surgical procedure. Method: The study was approved by the hospital ethics committee. 173 patients (195 joints) who underwent temporomandibular joint disc repositioning and anchoring surgery were selected for retrospective analysis. Patients were categorized into groups A (traditional preauricular incision-scalpel/tissue scissors anterior attachment release), 35 patients (40 joints), B (traditional preauricular incision-plasma bipolar radiofrequency electrode anterior attachment release), 42 patients (46 joints), C (revised tragus incision - scalpel/tissue scissors anterior attachment release), 50 patients (58 joints), and D (revised tragus incision-plasma bipolar radiofrequency electrode anterior attachment release), 46 patients (51 joints). After a 6-month postoperative follow-up, the differences in maximum mouth opening (MMO), visual analogue scale (VAS), effective rate of joint disc reduction, incidence of preauricular numbness, obvious scars among patients in each group at 1, 3, and 6 months were compared postoperatively. Results: After surgery, the MMO of all four groups of patients initially shrunk and then gradually increased compared to before surgery. At the 1-month follow-up after surgery, the plasma bipolar radiofrequency release (B+D) group had a smaller impact on the patient’s MMO compared to the surgical knife/tissue scissors release (A+C) group (P < 0.05). Postoperative VAS scores for all four groups showed a gradual decrease from pre-operative levels, with the (B+D) group scoring significantly lower in the first month post-surgery compared to the (A+C) group (P < 0.05). Six months post-surgery, the rate of joint disc reduction of the four groups were higher than 95%, with no significant differences observed between the groups (P > 0.05). Patients in the revised tragus incision (C+D) group experienced a lower rate of preauricular numbness compared to those in the traditional preauricular incision (A+B) group (4.59% vs. 12.79%, P < 0.05), The incidence of obvious scars in the (C+D) group was significantly lower than that in the (A+B) group (3.67% vs. 23.26%, P < 0.05). Conclusion The revised tragus incision is superior to traditional preauricular incision in terms of protecting the auriculotemporal nerve and the scars were more inconspicuous. Further, the plasma bipolar radiofrequency electrode is superior to the scalpel/tissue scissors in terms of mouth opening recovery and pain control. For temporomandibular joint disc reduction and anchoring surgery, a modified tragus incision combined with plasma bipolar radiofrequency electrode to release the anterior attachment of the joint disc can be recommended as a surgical option.

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

[Objective] To investigate and summarize the clinicopathological features, diagnosis, treatment and prognosis of adrenocortical carcinoma with rhabdoid features. [Methods] The clinical diagnosis and treatment of a case of adrenocortical carcinoma with rhabdoid features admitled to Department of Urology, Weifang People's Hospital were reported.The clinical manifestations, pathological features, diagnosis and prognosis of the disease were analyzed in combination with relevant literature. [Results] A 34-year-old male patient was admitted due to scrotal distension and pain that had persisted for 6 months.Imaging examination showed a huge soft tissue tumor in the left adrenal region of the retroperitoneum with compression displacement of the left kidney, leading to obstruction of venous return in the left spermatic vein, which in turn caused varicose veins.The levels of serum renin, angiotensin, aldosterone, cortisol, and catecholamine were within normal ranges.Surgical resection of the tumor was performed, and postoperative pathological examination revealed that the tumor tissue was predominantly composed of rhabdoid cells, exhibiting positive immunohistochemical staining for INI 1, Syn, Calretinin and Vimentin.Genetic testing did not identify any deletion of SMARCB1 and SMARCA4 mutations.Therefore, the diagnosis was adrenocortical carcinoma with rhabdoid features.At the current 20-month follow-up, no recurrence or metastasis was observed.A review of the literature found that only 7 cases of this disease had been reported. [Conclusion] Adrenocortical carcinoma with rhabdoid features is a rare disease, and a definitive diagnosis is dependent upon pathological examination.Surgical resection remains the primary treatment.Long-term follow-up is essential, and further research is needed to evaluate the impact of adjuvant therapy.

ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.