Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To analyze the application of antitoxin therapy in severe infant botulism.Methods:A retrospective analysis was conducted on 14 cases of severe infant botulism treated at 3 pediatric medical centers from July 2020 to August 2024. This study investigated antitoxin dosage, treatment duration, discontinuation criteria and adverse reactions.Results:A total of 14 cases (12 males and 2 females) were included, with an age of 5.0 (3.8, 7.0) months. Botulinum toxin typing revealed 10 cases of Type B, 2 cases of Type A and 2 untyped cases. The interval from symptom onset to antitoxin administration was 9.0 (6.0, 11.5) d. The initial dosage of type A antitoxin was 12 500 (10 000, 22 500) U, while type B was 5 000 (5 000, 5 000) U. The dosage was tapered in some cases after symptom improvement, the duration of treatment was 16.5 (9.8, 25.3) d. In total, 11 infants discontinued medications after improvement in muscle strength, while 3 infants discontinued treatment after obtaining negative results from fecal mouse bioassays. Adverse events were reported in 2 cases, both of which resulted in rash, and 1 case was complicated with anaphylactic shock. All the patients survived upon discharge with a follow-up period of 11 d to 3 years and 8 months. Totally 12 infants had fully recovered, while 2 infants were still recovering after discharge.Conclusion:Antitoxin therapy is a feasible and safe approach which showed favorable prognosis in severe infant botulism.

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

Objective:To explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin (LMWH) therapy for intensive care unit (ICU) patients.Methods:A retrospective case-control study was conducted. A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital, Sichuan University between January 31st, 2022, and November 30th, 2023, were enrolled in this study. The cohort comprised 264 males and 117 females, with the age of 58 (48, 71) years old. Clinical data and relevant laboratory parameters were collected, including anti-Ⅹa activity, antithrombin activity (AT), thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), conventional coagulation parameters such as activated partial thromboplastin time (APTT), and indicators of hepatic/renal impairment such as alanine aminotransferase (ALT) and creatinine( CREA). Patients were stratified into three groups based on thrombotic event: thrombosis-controlled, progressive thrombosis, and bleeding group. Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.Results:Among 381 patients, thrombosis was controlled in 213 (55.9%) patients, progressed in 81 (21.3%) patients , and bleeding events occurred in 87 (22.8%) patients. The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml): Only 35 (16.4%) cases in the thrombosis-controlled group, 16 (19.7%) cases in the progressive thrombosis group, and 16 (18.4%) in the bleeding group. No significant differences in anti-Ⅹ a levels activity among the three groups ( H=1.678, P=0.432). Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹ a activity levels (AT nadir, OR=1.031,95% CI 1.016-1.046, P<0.05). Compared with the progressive thrombosis and bleedinggroup, the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value ( H=8.519, P=0.014), and a higher proportion of TAT/PIC ratios below the cut-off ( H=15.56, P<0.001). Patients with bleeding demonstrated significantly lower AT activity ( H=14.968, P=0.001), prolonged APTT ( H=6.815, P=0.033), higher ALT ( H=13.774, P=0.001), and higher CREA ( H=14.068, P=0.001) compared with the thrombosis-controlled or progressive thrombosis group. Conclusion:Laboratory monitoring is required for low-molecular-weight heparin (LMWH) therapy in ICU patients. While anti-Ⅹa activity reflects the anticoagulant effect of LMWH, the utility of anti-Ⅹ a activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited. Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression. Furthermore, abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.

Objective:To explore the clinical efficacy of the first dorsal metatarsal artery pedicled lateral toe bilobed flap in repairing the finger pulp defects of two adjacent fingers.Methods:This study was a retrospective observational study. From January 2018 to December 2022, 9 patients with finger pulp defects in two adjacent fingers who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 6 males and 3 females, aged 26 to 48 years. The injured fingers were the index finger and middle finger (5 cases) or the middle finger and ring finger (4 cases). After debridement, the wound area of a single finger ranged from 1.2 cm×0.8 cm to 3.2 cm×2.8 cm. The finger pulp defects of two adjacent fingers were repaired with the first dorsal metatarsal artery pedicled lateral toe bilobed flap, and the two adjacent fingers were sutured together. The area of single flap ranged from 1.5 cm×1.0 cm to 3.5 cm×3.0 cm. The wound in the flap donor site was sutured directly or repaired with full-thickness skin graft from the groin region. The finger separation surgery was performed 3 weeks after surgery. The survival and blood supply of flaps, and survival of skin grafts and wound healing of the donor sites were observed after surgery. During follow-up, the texture, sliding, and shape of the flap, movement function of the finger, and the shape and function of the foot donor site were observed. At the last follow-up, the sensory of the flap was evaluated according to the sensory evaluation standard of the British Medical Research Council, and the hand function was evaluated according to the functional evaluation trial standard for severed finger replantation of the Hand Surgery Society of the Chinese Medical Association. Results:After surgery, all the flaps of 9 patients survived without vascular crisis. The flaps were soft in texture and good in shape. One patient had partial necrosis at the edge of the skin graft in the toe, and the wound healed after dressing change; the skin grafts in the toe in the other 8 patients survived, and the wounds healed well. During follow-up of 12 to 18 months after surgery, the flaps had soft texture, good elasticity, low sliding, and good shape. The finger movement function was normal. The wound in foot donor site recovered well without ulceration and deformity, and walking was not affected. At the last follow-up, the sensation of the flaps was sensitive, of which 8 flaps reached S3 and 10 flaps reached S3 + in sensation, and the two-point discrimination distance of the flaps was 9-13 mm. The functional scores of the affected fingers were 85 to 95, all of which were excellent. Conclusions:The first dorsal metatarsal artery pedicled lateral toe bilobed flap can repair finger pulp defects of two adjacent fingers at the same time, and the appearance, sensation, and function of the affected fingers recovered well after surgery, with less damage to the foot donor site. It is one of good methods to repair finger pulp defects of two adjacent fingers in clinic.

Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

Objective:To explore the medication law for threatened irritability in ancient gynecological monographs based on data mining.Methods:Based on Zhong Hua Yi Dian (5th edition), Chinese Medicine Resource Network and the paper version of ancient books, the representative gynecological monographs from the pre-Qin to the Qing Dynasty were selected to retrieve the prescriptions for the treatment of fetal irritability and establish a database. Excel 2019, IBM SPSS Modeler 18.0 and IBM SPSS Statistics 26.0 software were used to perform frequency statistics, association rule analysis and clustering analysis on the data of Chinese materia medica, analyze the core drug groups, and explore the medication laws. Results:A total of 151 prescriptions were included, including 7 kinds of TCM syndrome types, involving 111 kinds of Chinese materia medica. The most commonly used Chinese materia medica were Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Chuanxiong Rhizoma, and Paeoniae Radix Alba, etc. The efficacy categories were mainly tonic, heat-clearing, blood-activating and stasis-resolving; the medicinal properties were mainly warm and neutral; the tastes were mainly sweet and pungent; the main meridians were spleen, lung, liver and kidney meridians. 17 commonly used TCM combinations were obtained by association rule analysis, and five core TCM combinations were obtained by clustering analysis.Conclusions:In the treatment of threatened irritability, ancient doctors used the method of tonifying kidney and invigorating spleen, tonifying qi and nourishing blood, clearing heat and preventing miscarriage flexibly. The core drugs were mainly Angelicae Sinensis Radix, which was mostly modified on the basic prescriptions such as Siwu Decoction and Jiaoai Decoction.

ObjectiveTo investigate the characteristics of injury deaths and its disease burden in Taizhou City from 2009 to 2022, and to provide a basis for the prevention and control of injury. MethodsBased on the injury death surveillance data of Taizhou City from 2009 to 2022, the age-specific and sex-specific mortality rates, as well as the standardized mortality rates after adjusting China’s standardized population age of residents in Taizhou City were calculated. The crude mortality rate, standardized mortality rate, average years of life lost(AYLL), potential years of life lost (PYLL) and potential years of life lost rate (PYLLR) were calculated using Excel 2013 software. Joinpoint 4.2 software was used to estimate the annual percentage change (APC) and analyze the trends of injury mortality and PYLLR from 2009 to 2022. ResultsFrom 2009 to 2022, the standardized mortality rate of injuries in Taizhou City showed a decreasing trend (APC=-4.876%, P<0.001), with a mortality rate of 64.38/100 000 and a standardized mortality rate of 66.68/100 000. There was a statistically significant difference in injury deaths by genders (χ²=7 520.153, P<0.001). From 2009 to 2022, the PYLL and AYLL caused by injuries in Taizhou City were 587 518 person years and 21.91 years, respectively, with a PYLLR of 7.72%. The PYLLR of injuries showed a decreasing trend (APC=-7.454%, P<0.001), in addition, the PYLLR in urban(APC=-7.123%), rural areas (APC=-10.193%), males (APC=-7.595%) and females (APC=-7.046%) all showed a decreasing trend, all differences were statistically significant(all P<0.001). The top five causes of injury deaths leading to PYLL were traffic accident, drowning, accidental fall, suicide and accidental poisoning. ConclusionIn the last decade, injury has been a major cause leading to premature death among residents in Taizhou, with a higher mortality rate in males than that in females, and different injury characteristics caused by different types of injuries. It is necessary to take targeted injury prevention and intervention measures for different key population groups to effectively reduce the disease burden caused by injury deaths.

Objective:To explore the efficacy and adverse reactions of sacituzumab govitecan (SG) in the posterior-line therapy for advanced malignant tumors.Methods:A retrospective case series study was conducted. The clinicopathological data of 20 patients with advanced malignant tumors who were treated with SG after multiple lines of treatment in Nanjing BenQ Hospital From July to December 2023 were retrospectively analyzed. The short-term efficacy and treatment-related adverse events (TRAE) were evaluated.Results:Among the 20 patients, there were 7 males and 13 females, the median age [ M ( Q1, Q3)] was 60.0 (53.8, 72.5) years old, the median line of previous anti-tumor regimens was 4.5 (3.3, 6.0) lines, and the median duration time of SG treatment was 52.5 (35.8, 72.5) days. After SG treatment, there were 3 cases (15.0%) with partial response, including breast cancer, vaginal squamous cell carcinoma and endometrial carcinoma, 10 cases (50.0%) with stable disease and 7 cases (35.0%) with progressive disease. The objective response rate was 15.0% (3/20), and the disease control rate was 65.0% (13/20). Two cases (10.0%) were discontinued due to intolerable adverse reactions. The incidence of TRAE was 75.0% (15/20), of which the incidence of ≥grade 3 TRAE was 10.0% (2/20), including neutropenic fever and ventricular arrhythmia. Conclusions:SG has a certain therapeutic effect and controllable safety in the posterior-line therapy for advanced malignant tumors.