ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

OBJECTIVES: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.
Endoplasmic Reticulum Chaperone BiP ; Lupus Nephritis/blood* ; Transcription Factor CHOP/blood* ; Heat-Shock Proteins/blood* ; Animals ; Apoptosis ; Humans ; Mice ; Mice, Inbred MRL lpr ; Female ; Adult ; Endoribonucleases/metabolism* ; Male ; eIF-2 Kinase/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Young Adult ; Endoplasmic Reticulum Stress ; Kidney/metabolism* ; Middle Aged ; Signal Transduction

Objective:To prepare the nanodrug paclitaxel dimer(PTX2)-loaded nanoparticles(NPs)using the block copolymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000,(DSPE-PEG2000),and to explore the killing effect of PTX2 NPs on the human lung cancer A549 cells and its influence on apop to tis.Methods:The PTX2 NPs were prepared using nanoprecipitation method.Dynamic light scattering(DLS)was employed to determine the particle size distribution,and transmission electron microscope(TEM)was used to observe the ultrastructure of the nanoparticles.After treatment of 0 and 10 mmol·L-1 dithiothreitol(DTT),dialysis method was used to evaluate the in vitro drug release profile of PTX2 NPs.The cell counting kit-8(CCK-8)method was used to assess the survival rates of the A549 cells after treated with PTX2 and PTX2 NPs with different concentrations(0.000 1,0.001 0,0.010 0,0.100 0,and 1.000 0 μmol·L-1).The A549 cells were divided into control group,PTX2 group,and PTX2 NPs group.Live/dead staining method was used to detect the survival of the A549 cells in various groups,and flow cytometry was used to detect the apoptotic rates of the A549 cells in various groups.Results:The mean hydrodynamic diameter of PTX2 NPs was determined to be 144.7nmbyDLS.TheTEM imaging confirmed uniform spherical morphology of PTX2 NPs.In a reductive environment,the PTX2 NPs exhibited continuous drug release with total paclitaxel(PTX)release of 84％within 72 h.The results of CCK-8 method showed that both PTX2 and PTX2 NPs inhibited the proliferation of A549 cells in a dose-dependent manner.When the concentrations of PTX＜0.01 μmol·L-1,compared with PTX2 group,the survival rates of A549 cells in PTX2 NPs group were significantly decreased(P＜0.01 or P＜0.001).The live/dead staining results showed that compared with PTX2 group,the number of red fluorescence-labeled dead cells in PTX2 NPs group was increased.The flow cytometry results demonstrated that compared with control group and PTX2 group,the apoptotic rates of the A549 cells in PTX2 NPs group were significantly increased(P＜0.05 orP＜0.01).Conclusion:The PTX2-loaded nanoparticles PTX2 NPs are successfully prepared which exhibits responsive drug release and demonstrates a more significant killing effect on the human lung cancer A549 cells compared to PTX2.

Objective To investigate the value of nutritional status control(CONUT)score,platelet to albumin ratio(PAR)and mean platelet volume to lymphocyte ratio(MPVLR)before treatment on immunotherapy efficacy and immune-related adverse reactions(irAEs)in advanced gastric cancer patients.Methods A total of 113 patients with advanced gastric cancer admitted to the hospital from January 2020 to June 2023 were selected as the gas-tric cancer group,and 113 healthy volunteers were selected as the control group.According to the efficacy of immunotherapy,the patients with advanced gastric cancer were divided into effective group(70 cases)and in-effective group(43 cases),and divided into irAEs group(51 cases)and non-irAEs group(62 cases)according to whether irAEs occurred.The factors influencing the occurrence of irAEs in advanced gastric cancer were analyzed,and the value of CONUT score,PAR and MPVLR before treatment in predicting the efficacy of im-munotherapy and irAEs in advanced gastric cancer was analyzed.Results The CONUT score,PAR and MPV-LR in gastric cancer group before treatment were higher than those in control group(P＜0.05).The CONUT score,PAR and MPVLR before treatment in the ineffective group were higher than those in the effective group(P＜0.05).The area under the curve(AUC)of CONUT score,PAR and MPVLR alone in predicting the ineffective immunotherapy in advanced gastric cancer patients before treatment were 0.779,0.739 and 0.766,respectively,the AUC predicted by combined detection was 0.889,which was higher than that predic-ted by alone(P＜0.05).The CONUT score,PAR and MPVLR before treatment in irAEs group were higher than those in non-irAEs group(P＜0.05).The age of irAEs group was lower than that of non-irAEs group(P＜0.05),and the proportion of Ki-67 index,CD4+T lymphocytes and Treg cells was lower than that of non-irAEs group(P＜0.05).The increase of CONUT score,PAR and MPVLR before treatment were risk factors for irAEs in advanced gastric cancer patients(P＜0.05),and the increase of Treg cell proportion was a protective factor(P＜0.05).The AUC of CONUT score,PAR and MPVLR alone in predicting the occurrence of irAEs in advanced gastric cancer patients before treatment was 0.816,0.798 and 0.783,respectively,the AUC predic-ted by combined detection was 0.887,which was higher than that predicted alone(P＜0.05).Conclusion The CO-NUT score,PAR and MPVLR before treatment are significantly increased in advanced gastric cancer patients,and are associated with ineffective immunotherapy and the occurrence of irAEs.The combined detection of the three indicators can effectively predict the immunotherapy efficacy and irAEs in advanced gastric cancer pa-tients.

Objective To evaluate the results of anorectal dynamics in patients with severe rec-tocele.Methods A retrospective analysis was conducted on the clinical data of 38 patients defini-tively diagnosed with severe rectocele at the pelvic floor center of the anorectal department of Nanjing Hospital of Traditional Chinese Medicine from January 2020 to January 2023.All patients underwent anorectal manometry,and the results of anorectal dynamics were analyzed.Results A total of 15 pa-tients(39.47％)had elevated anal resting pressure(ARP),20(52.63％)had normal ARP,and 3(7.89％)had decreased ARP.Five patients(13.16％)had elevated maximum anal sphincter pressure(MASP),9(23.68％)had normal MASP,and 24(63.16％)had decreased MASP.Nor-mal defecation relaxation reflex was observed in 15 patients(39.47％),and abnormal defecation re-laxation reflex was observed in 23 patients(60.53％).Ten patients(26.32％)had normal rectal defecation pressure,and 28(73.68％)had decreased rectal defecation pressure.Eleven patients(28.95％)had elevated rectal initial sensory threshold(RIST),27(71.05％)had normal RIST.Fifteen patients(39.47％)had elevated rectal defecation sensory threshold,21(55.26％)had normal rectal defecation sensory threshold,and 2(5.26％)had decreased rectal defecation sensory threshold.Three patients(7.89％)had elevated rectal maximum tolerable volume,26(68.42％)had normal rectal maximum tolerable volume,and 9(23.68％)had decreased rectal maximum tolerable vol-ume.ARP was moderately positively correlated with the chronic constipation severity(CSS)score(P=0.007,r=0.429),and abnormal defecation relaxation reflex was moderately negatively correla-ted with the CSS score(P=0.019,r=-0.329).In 3 patients(7.89％),both ARP and MASP were decreased,and both ARP and MASP were elevated in 5 patients(13.16％).Conclusion Pre-operative anorectal dynamics analysis is necessary for patients with severe rectocele to formulate a reasonable individualized surgical plan and postoperative rehabilitation program.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective:To analyze the current preparation and usage situation of first-aid drugs in the rescue vehicles in children's medical institutions, and provide references for optimizing the list of emergency drugs.Methods:First-aid drug lists in the rescue vehicles of 12 children's medical institutions from 11 provinces and municipalities in China were collected through questionnaire surveys, and the drugs as well as their quantities were compared. The existing problems in the use of first-aid drugs in the 12 medical institutions were investigated by on-site interviews. The usage information of first-aid drugs in the rescue vehicles of the General Surgery and Cardiology Department of Shanxi Children's Hospital from May 2022 to April 2023 was collected through the hospital information center, and usage frequency and dosage per patient of the drugs were calculated. Descriptive statistical analysis was conducted on the collected data.Results:The first-aid drug lists in 12 hospitals were various, including 7 to 22 kinds of drugs and involving a total of 23 drugs. These mainly included vasoactive drugs, cardiotonic drugs, antiarrhythmic drugs, antiangina and anti-ischemic drugs for the heart, antispasmodic drugs, diuretics, dehydrating drugs, sedative-hypnotic drugs, and glucocorticoids, all of which were injections. The drugs that were included in all the lists of 12 hospitals were epinephrine, dopamine, dexamethasone, furosemide, and atropine. The drug lists of different rescue vehicles throughout the hospital were the same in 4 hospitals, while the lists varied among departments based on their specific clinical needs in the other 8 hospitals. None of the 12 hospitals had a first-aid drug usage manual. The on-site interview results showed that, the existing problems about drug preparation and use in rescue vehicles mainly involved the following 6 aspects: drug types, quantities, labels, storage, procurement, and usage. In Shanxi Children's Hospital, the types and quantities of first-aid drugs in rescue vehicles of General Surgery Department and Cardiology Department were the same. There were 6 and 9 kinds of drugs were used in the 2 departments during rescue operations, respectively. The drugs that were never used in either department included promethazine, lidocaine, diazepam, phenobarbital, raceanisodamine, sodium bicarbonate, atropine, glucose, and calcium gluconate.Conclusions:The phenomenon of unreasonable kinds and quantities of first-aid drugs in the rescue vehicles existed in the children's medical institutions, and the drugs provided did not fully match the actual clinical needs. There was an urgent need for preparation guidelines and usage manuals of first-aid drugs that were suitable for children's medical institutions to enhance the scientificity of drug supply and the correctness of usage.