Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

Objective:To examine the perioperative safety of laparoscopic cholecystectomy in human immunodeficiency virus (HIV)-positive patients undergoing antiretroviral therapy.Methods:A retrospective cohort study method was employed to collect clinical data from 388 patients with gallstones who were admitted to Department of General Surgery of the Provincial Hospital of Anhui Medical University between January 2020 and December 2023. The cohort comprised 135 males and 253 females. For the purpose of analysis, the participants were divided into HIV-positive group ( n=25) and HIV-negative group ( n=363). The distinction between the two groups was based on whether the participants were co-infected with HIV. The clinical and pathological data pertaining to the two groups of patients, along with the intraoperative and postoperative data, were collated. The propensity score matching method was employed to control for confounding bias, and the data on anaesthesia methods, intraoperative blood loss, duration of surgery, necessity for conversion to laparotomy, postoperative complications, postoperative drainage volume, postoperative hospital stay, and total treatment costs were compared between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared using the t-test. Measurement data with skewed distribution were expressed as M( Q1, Q3) and compared using the rank-sum test. The Fisher exact probability method or the chi-square test was employed for the comparison of count data. Results:The two groups of general data were found to be statistically significant in terms of gender, preoperative red blood cells, neutrophils, alanine aminotransferase, and indirect bilirubin exhibited statistically significant differences( P<0.05). Following propensity score matching, a total of 59 cases were identified. Of these, 25 cases were observed in the HIV-positive group, while 34 cases were observed in the HIV-negative group. No statistically significant differences were observed between the two groups with respect to the general data ( P>0.05). No statistically significant difference was observed between the two groups in terms of anaesthesia method, intraoperative blood loss, duration of surgery, need for conversion to laparotomy, postoperative complication rate, postoperative drainage volume and postoperative hospital stay ( P>0.05). The total length of hospital stay and total hospital expenses in the HIV-positive group were 5.0 (3.0, 7.0) days and (14 829.3±4 852.8) yuan, respectively. HIV-negative group were 3.0 (2.0, 4.8) days and (10 762.3±1 850.3) yuan, respectively. The HIV-negative group had a significantly shorter hospital stay and lower hospital expenses, these differences were statistically significant ( P<0.05). There was no occupational exposure of medical personnel in the perioperative period among those with HIV. Conclusions:Laparoscopic cholecystectomy is a safe and feasible procedure for HIV-positive patients who are receiving antiretroviral therapy. Adherence to established protocols by healthcare personnel can mitigate the risk of occupational exposure.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P＜0.05),reduced the apoptosis of retinal cells(P＜0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P＜0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P＜0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.

Apoptosis is a process of programmed cell death,which has the function of maintaining skin balance.In psoriasis,the disturbance of apoptosis is characterized by abnormal prolif-eration of keratinocytes.Traditional Chinese medicine(TCM)has a regulatory effect on keratinocyte apoptosis,which can in-hibit the excessive proliferation of psoriasis epidermis,promote normal epidermal differentiation,and maintain epidermal homeo-stasis.It has the advantages of fewer adverse reactions and multi-targets.Therefore,this article summarizes and analyzes the specific mechanism of various active ingredients of TCM to in-duce the apoptosis of psoriasis keratinocytes by interfering with related factors and signaling pathways,hoping to provide a refer-ence for the treatment of psoriasis with TCM.

Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P＜0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.

Objective:To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI).Methods:Based on the American Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ), clinical data of S-AKI patients from 2008 to 2021 were collected.Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7∶3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds.Results:Based on the survival status at 3 months after diagnosis, patients were divided into 7?768 (68.54%) survivors and 3?566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95% CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95% CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95% CI was 0.56-0.58) and SIRS score's 0.56 (95% CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. Conclusions:A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC-Ⅳ and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.

Objective:To explore the potential impact of lipid metabolism-related single nucleotide polymorphisms(SNP)on semen quality in men.Methods:We selected 284 semen samples from Xingtai Infertility Hospital and Hebei Human Sperm Bank collected between February and October 2023,33 from oligozoospermia(OS),97 from asthenozoospermia(AS)and 54 from oligoas-thenozoospermia(OAS)patients and the other 100 from normal men.We performed computer-assisted semen analysis(CASA)of the samples,extracted blood DNA and,using the Mass ARRAY? System,genotyped the target genes,determined the genotypes of 13 SNPs and compared their distribution,their correlation with BMI and semen quality in different groups.Results:The mutant homozygous(TT)genotype of the FADS2 rs2727270 gene seemed to be a risk factor for AS(OR=4.420,P=0.047),while the APOA2 rs5082-A allele and MC4R rs17782313 heterozygous(TC)genotype important protective factors for OS(OR=0.422 and 0.389;P=0.045 and 0.043,respectively).A significantly higher sperm concentration was found associated with the MC4R rs17782313 heter-ozygous(TC)genotype than with the homozygous(CC)genotype.Stratification analysis showed that the protective effect of the TC genotype was decreased with increased BMI and remained with the interaction of the rs5082 and rs17782313 genotypes.Conclusion:FADS2 rs2727270,APOA2 rs5082 and MC4R rs17782313 were significantly correlated with the risk of abnormal semen parameters.