ObjectiveTo investigate the mechanism by which Sini San （SNS） treats liver fibrosis through regulating the polarization of intrahepatic Kupffer cells. MethodsSixty SPF-grade male Balb/c mice were randomized into blank control， model， silymarin （0.2 g·kg^-1）， and low-， medium-， and high-dose （2.93， 5.85， 11.70 g·kg^-1， respectively） SNS groups. A mouse model of liver fibrosis was induced by intraperitoneal injection of CCl₄. After 5 weeks of administration， the body mass， liver pathological changes ［Hematoxylin and Eosin （HE）， Masson， and Sirius red staining］， serum biochemical indicators ［alkaline phosphatase （ALP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）］， liver fibrosis markers ［procollagen type Ⅲ （PCⅢ）， laminin （LN）， and hyaluronic acid （HA）］， inflammatory cytokines ［interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10）］， and fibrosis-related proteins ［α-smooth muscle actin （α-SMA）， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ）］ were assessed. A co-culture system of THP-1 cells （M1 macrophages） and human hepatic stellate cells （LX-2） was established. The cell experiment was designed with blank control （LX-2 alone）， model （LX-2 + M1 macrophages）， and low-， medium-， and high-dose SNS （co-culture with 5%， 10%， or 20% SNS-containing serum， respectively） groups. Cell viability， inflammatory cytokines， and macrophage phenotype were examined. Human primary hepatic Kupffer cells were allocated into blank control， M1 （LPS 100 μg·L^-1+IFN-γ 20 μg·L^-1）， M2 （IL-4 20 μg·L^-1+IL-13 20 μg·L^-1）， M1+M2， M1+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M1 conditions for 24 h）， M2+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M2 conditions for 24 h）， and M1+M2+SNS groups （supplemented with 10% SNS-containing serum for 2 h after culture under M1+M2 conditions for 24 h）， and the expression of nuclear factor-κB （NF-κB） p65 and signal transducer and activator of transcription 3 （STAT3） at protein and mRNA levels was determined. ResultsCompared with the blank group， the model group exhibited increased serum levels of ALT， AST， ALP， PCⅢ， LN， HA， IL-6， and TNF-α， upregulated protein and mRNA levels of α-SMA， Col Ⅰ， and Col Ⅲ in the liver tissue （P<0.05， P<0.01）， and decreased IL-10 level and STAT3 mRNA level （P<0.05， P<0.01）， accompanied by marked collagen deposition and inflammatory infiltration in the liver. Compared with the model group， all doses of Sini San reversed these alterations （P<0.05， P<0.01）， with the high-dose group showing the most pronounced effects. Cell experiments demonstrated that， compared with the blank control group， the model group had elevated levels of pro-inflammatory cytokines （IL-1β， IL-6， and TNF-α） and upregulated protein and mRNA levels of M1 markers ［cluster of differentiation 86 （CD86， inducible nitric oxide synthase （iNOS）， and monocyte chemoattractant protein-1 （MCP-1）］ （P<0.01）， along with declined level of IL-10 and downregulated expression of M2 markers ［（CD163， CD206， and arginase-1 （Arg-1）］ （P<0.05，P<0.01）. Compared with the model group， treatment with Sini San-containing serum at various concentrations lowered the levels of pro-inflammatory cytokines and expression of M1 markers （P<0.05， P<0.01）， while increasing the IL-10 level and M2 marker expression （P<0.05， P<0.01）. Additionally， Sini San downregulated the mRNA level of NF-κB and upregulated the mRNA level of STAT （P<0.05， P<0.01）. In the experiment with human primary Kupffer cells， compared with the blank group， the M1 group showed increased NF-κB p65 expression （P<0.01） and decreased STAT3 expression （P<0.05）， whereas the M2 group exhibited increased STAT3 expression （P<0.01）. Compared with the respective model groups， Sini San-containing serum reversed the M1-induced overexpression of NF-κB p65 （P<0.05， P<0.01） and further enhanced the M2-induced STAT3 expression （P<0.05， P<0.01）. ConclusionSini San can inhibit the NF-κB p65/STAT3 signaling pathway and repolarize intrahepatic Kupffer cells from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype to attenuate inflammation and suppress hepatic stellate cell activation and collagen deposition， thereby exerting anti-fibrotic effect.

The research on artificial womb technology and “fetus and newborn” by Deby et al.， as well as the Food and Drug Administration’s discussion on whether the world’s first human clinical trial of “artificial womb” technology should be approved， have sparked a new wave of research on artificial womb technology. By extending and deepening relevant foreign research， the three potential application prospects of artificial womb technology were clarified， including rescuing extremely preterm infants， reducing the burden of pregnancy， and assisting advanced maternal age. The ethical risks it faced were pointed out， encompassing the moral status of the gestational entity was questionable， and the risks of technological experimentation could not be quantified. The governance pathways were clarified， involving multi-layered ethical considerations to complete the clear identification of the gestational entity’s identity， and multi-faceted patient-doctor consultations to achieve clear risk notification. Through discussions on the application prospects， ethical risks， and governance pathways of artificial womb technology can improve human welfare and realize the technology for human use.

Objective:To compare postoperative anal function recovery between laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis for slow transit constipation.Methods:This multicenter retrospective cohort study enrolled patients meeting the following criteria: (1) severe constipation symptoms (<2 bowel movements/week), absent or insignificant defecation urge, abdominal distension, requiring laxatives to maintain bowel movements or laxatives being ineffective; (2) constipation symptoms for over 5 years, ineffective after >2 years of medical treatment, with strong desire for surgery; (3) significantly prolonged colon transit time (>72 hours) without significant gastric or small intestinal transit dysfunction; (4) no organic colonic lesions confirmed by colonoscopy and abdominal CT. Exclusion criteria: (1) patients undergoing open surgery; (2) exclusion of outlet obstruction constipation (e.g., rectocele, rectal prolapse, puborectalis spasm) by functional defecation MRI; (3) comorbid psychiatric disorders; (4) missing clinical data or loss to follow-up (postoperative follow-up <24 months). Based on these criteria, clinical and follow-up data were collected from 220 patients who underwent either laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (LSC group, n = 115) or laparoscopic total colectomy with ileorectal anastomosis (LTC group, n = 105) for slow transit constipation between January 2013 and December 2022. Subjective anal function (Constipation Severity Score and Wexner Fecal Incontinence Score) and objective anal function (positive rate of rectoanal inhibitory reflex [RAIR] and anorectal manometry) were observed preoperatively and at 6, 12, and 24 months postoperatively. Results:No significant differences were found in baseline characteristics between the two groups (all P >0.05). All surgeries were completed successfully without major significant complications. Subjective anal function assessment: At 24 months postoperatively, Constipation Severity Scores decreased significantly compared to preoperative scores in both groups [LSC group: (25.2±2.8) vs. (2.9±1.8), P <0.001; LTC group: (25.8±2.9) vs. (2.8±1.9), P<0.001]. No significant differences were found between the groups at 6, 12, and 24 months postoperatively (all P>0.05). Wexner Fecal Incontinence Scores at 24 months were significantly lower than those at 6 months in both groups [LSC group: (12.9±1.8) vs. (3.9±2.5), P<0.001; LTC group: (12.6±1.8) vs. (5.4±2.4), P<0.001]. Although no significant difference was found at 6 months ( P = 0.190), the LSC group had significantly lower Wexner scores than the LTC group at 12 and 24 months postoperatively (both P < 0.001). Objective anal function assessment: (1) Positive RAIR rate: Preoperative positive RAIR rates were 33.0% (38/115) in the LSC group and 25.7% (27/105) in the LTC group ( P > 0.05). At 24 months, positive rates increased significantly in both groups [LSC: 66.1% (76/115); LTC: 63.8% (67/105)] compared to preoperative rates (both P<0.001), but no significant differences were found between groups at 6, 12, and 24 months (all P>0.05). (2) Resting pressure (RP) and squeeze pressure (SP): No significant differences were found in preoperative RP and SP between groups (all P>0.05). The LSC group had significantly higher RP and SP than the LTC group at 6 and 12 months postoperatively (all P<0.05), but no significant differences were found at 24 months ( P>0.05). Conclusion:Both laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis and laparoscopic total colectomy with ileorectal anastomosis are safe for patients with slow transit constipation. However, laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis offers superior postoperative anal function recovery.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective To evaluate the efficacy of transcatheter arterial chemoembolization(TACE)combined with argon-helium cryoablation(AHC)in the treatment of hypervascular small hepatocellular carcinoma(sHCC).Methods The clinical data of 35 patients with hypervascular sHCC,who received TACE combined with AHC at the Affiliated Cancer Hospital of Zhengzhou University of China from March 2018 to February 2019,were retrospectively analyzed.All patients were treated with TACE treatment first,after 3-7 days the patients received AHC therapy.The postoperative 1-,3-,and 6-month curative effect were evaluated,and the postoperative 1-,3-,and 5-year survival rates were calculated.The liver function and immune function indicators,as well as the serum tumor markers were detected.The adverse reactions during treatment were recorded.Results The postoperative 1-,3-,and 6-month objective remission rate(ORR)were 100.00％,94.29％and 91.43％respectively,and the disease control rate(DCR)were 100.00％,100.00％and 97.14％ respectively.The overall survival(OS)was(46.54±2.88)months,and the postoperative 1-,3-,and 5-year survival rates were 94.29％(33/35),65.71％(23/35)and 48.57％(17/35)respectively.The postoperative 3-day serum levels of ALT,AST and TBIL were significantly elevated when compared with their preoperative baseline levels(all P＜0.05),which returned to preoperative levels in 2 weeks after treatment(P＞0.05).The postoperative 2-week CD4+％and CD4+％/CD8+％ratio were remarkably increased when compared with their preoperative values(both P＜0.05),while the postoperative 2-week AFP,AFP-L3％,DCP and GPC3 levels were strikingly decreased when compared with their preoperative values(all P＜0.001).None of the patients developed procedure-related severe complications after treatment.Conclusion For the treatment of hypervascular sHCC,TACE combined with AHC has satisfactory clinical efficacy and safety.

Objective To investigate the effect of toripalimab combined with chemoradiotherapy in patients with cervical lymph node metastasis of nasopharyngeal carcinoma on immune function.Methods A prospective study was conducted in 160 patients with nasopharyngeal carcinoma accom-panied by cervical lymph node metastasis.Patients were divided into study group and control group using block randomization,with 80 patients in each group.The control group received a standard che-moradiotherapy regimen,while the study group received toripalimab combined with chemoradiothera-py.Both groups were treated for 3 courses.The clinical efficacy,levels of immune function indica-tors,levels of tumor markers[squamous cell carcinoma antigen(SCC-Ag),high-mobility group box 1(HMGB1),pentraxin 3(PTX3),and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)],and the incidenceof adverse reactions were compared between the two groups.Results The objective re-sponse rates of the primary lesion and cervical lymph nodes in the study group were higher than those in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and natural killer cells in the study group were higher than those before treatment and in the control group,while the lev-el of CD8+was lower than that before treatment and in the control group(P＜0.05).After treatment,the levels of HMGB1,PTX3,SCC-Ag and CYFRA21-1 in the study group were lower than those before treatment and in the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Toripalimab combined with chemoradiotherapy has a sig-nificant efficacy in treatment of cervical lymph node metastasis of nasopharyngeal carcinoma.It can enhance the immune function of patients,improve the levels of tumor markers,and has good safety.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Objective To investigate the the levels of magnesium,lead,iron,zinc,copper,manganese,calci-um in whole blood in children aged 0-12 years in Henan province,understand the health status of children and provide a basis for their nutrition and health management.Methods Data were collected from totally 135 385 children aged 0-12 years who underwent trace element testing at Zhengzhou Kingmed Clinical Labo-ratory Inc.from 2019 to 2023 were selected,and agilent inductively coupled plasma mass spectrometer was used to detect seven elements(magnesium,lead,iron,zinc,copper,manganese,and calcium).The elemental detection method in the laboratory has been strictly methodologically verified,and has participated in the ex-ternal quality assessment organized by National Center for Clinical Laboratories.Grouping was conducted based on gender,age,season,region,and year to compare the deficiencies and lead exceedances of six elements(magnesium,iron,zinc,copper,manganese,calcium)under different conditions.Results In this study,the mean P-values of seven elements in different age groups,gender groups,year groups,and regional groups were all＜0.001.Except for lead with a P-value of 0.002,all other elements in different season groups were＜0.001.The P-values were all less than 0.05,indicating statistically significant differences.Among them,Mag-nesium,iron,and zinc in children's whole blood showed an increasing trend with age,while copper,manga-nese,and calcium showed a decreasing trend with age.The proportions of children aged 0-1 years with iron,zinc,and manganese deficiencies were the highest,at 24.70％,48.20％,and 0.65％,respectively.The highest proportion of copper and calcium deficiency was in the age range of 11-12 years old,accounting for 20.43％and 0.17％respectively.The highest proportion of lead exceeding the standard was 0.87％among children aged 0-1.Except for manganese and calcium levels,the levels of the other five elements were higher in boys than in girls.Magnesium and copper levels were highest in spring,iron,zinc,and calcium levels were highest in winter,and manganese and lead levels were highest in summer.Magnesium deficiency,calcium deficiency,and lead excess were showing a decreasing trend year by year.Among them,the lead levels of children in Sanme-nxia and Jiyuan were relatively high compared to other areas.Conclusion 0-2 years children are mainly char-acterized by calcium and zinc deficiency in Henan province.Attention should be paid to iron and zinc supple-mentation in infants and young children.At the same time,it should also be noted that the deficiency rate of copper increases with age,and attention should be paid to the supplementation of copper in children.

Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

Objective:To investigate the clinical outcomes of arthroscopic suture anchor fixation for acute bony Bankart lesions.Methods:Data of 49 patients with acute bone Bankart injury treated with suture anchor fixation under arthroscopy at the Affiliate Nanjing Drum Tower Hospital of Nanjing University School of Medicine from February 2019 to July 2024 were retrospectively analyzed, including 34 males and 15 females, aged 46.4±17.7 years (range, 18-81 years). Body mass index was 26.3±4.2 kg/m 2 (range, 19.8-37.9 kg/m 2). There were 17 patients with left shoulder and 32 patients with right shoulder. The time from injury to operation was 12.6±10.5 d (range, 1-50 d). CT three-dimensional reconstruction showed that the area of bone defect accounted for 20.1%±11.4% (range, 8%-49%) of the glenoid area. According to the degree of bone defect, there were 38 cases in the bone defect area ≤25% group and 11 cases in the bone defect area >25% group. All 49 patients received shoulder arthroscopic fixation with wire anchor. All 49 the patients were treated under shoulder arthroscopy using suture anchor technique. Using American Shoulder & Elbow Surgeon (ASES) score, University of California, Los Angeles (UCLA) score, Rowe score as well as shoulder range of motion to evaluate shoulder function. The position and healing of the fracture mass were evaluated with shoulder joint CT and three-dimensional reconstruction at immediate and final follow-up. Results:The incision healed in one stage and no infection occurred in all patients. All 49 patients were followed up for a period of 3 to 81 months, with an average follow-up of 23.8±20.2 months. At the final follow-up, the mean forward elevation, external rotation, and internal rotation improved from 126.1°±20.3°, 36.9°±14.0°, and 10±2 preoperatively to 167.1°±15.5°, 66.8°±8.3°, and 6±1 at the last follow-up, respectively ( P<0.05). At the final follow-up, the mean ASES score, UCLA score, and Rowe score were all significantly improved from 41.3±11.9, 14.2±6.1 and 46.9±14.7 preoperatively to 89.7±7.8, 31.5±3.6 and 92.4±7.4, respectively ( P<0.05). The differences between the final follow-up and preoperative values for forward elevation in the bone defect area >25% group and the bone defect area ≤25% group were 43°±20° and 41°±21°, respectively. The differences in lateral external rotation were 34°±8° and 29°±18°, while the differences in internal rotation (measured by hand-behind-back reach) were 5±2 and 4±2, respectively. None of these differences were statistically significant. The differences between the final follow-up and preoperative scores in the bone defect area >25% fracture fragment group and the bone defect area ≤25% group were as follows: ASES score, 50.9±14.4 vs. 47.7±12.8; UCLA score, 18.4±3.2 vs. 17.0±6.9; and Rowe score, 40.5±13.5 vs. 46.9±15.0. None of these differences were statistically significant. CT examination at the last follow-up showed that all fractures were healed, all patients in the bone defect area ≤25% group achieved good reduction, and 3 patients in the bone defect area >25% group had step-offs on the glenoid surface. Postoperative shoulder adhesion occurred in 5 patients, which was improved after intensive abduction and external rotation exercise. Conclusions:Arthroscopic suture anchor fixation is effective for the bone defect area ≤25% bony Bankart lesions, offering advantages of minimal invasiveness and rapid recovery. For lesions involving more than the bone defect area 25% of the glenoid surface, enhanced fixation strength is recommended to prevent fracture fragment displacement.