End-stage liver disease (ESLD) covers the end-stage of acute and chronic liver diseases, mainly involving decompensated cirrhosis, various types of liver failure, and advanced liver cancer. Hepatocyte transplantation has shown promise in treating ESLD, but its clinical application is hampered by the shortage of donor hepatocytes. Cell therapy, an emerging effective treatment for ESLD, faces the same limitation due to scarce hepatocyte availability. Hepatocyte-like cells (HLCs), which are terminally differentiated cells, can be induced from both stem cells and somatic cells. As HLCs exhibit the morphology and function of primary hepatocytes, they offer a promising supplementary source of hepatocytes for cell therapy. First, we provide a background for the differentiation and maturation of primary hepatocytes. Subsequently, based on the current insights into the molecular pathways that regulate hepatocyte differentiation in vivo, we describe a strategy for establishing HLC derived from either stem cells or somatic cells. The key characteristics of these HLCs are also detailed. Furthermore, HLC offers therapeutic potential for liver failure, and HLC-based liver organoids and bioartificial liver systems have demonstrated the ability to provide liver functions, offering an innovative approach to treating various types of ESLD. Despite their promise, challenges such as efficiency in differentiation and functional maturation need to be addressed to improve the clinical application of HLCs. This review discusses these advancements and outlines the therapeutic potential and current challenges of HLC therapy for ESLD.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

The randomized controlled trials (RCTs) regarding acupuncture direction published from January 1st, 2013, to November 7th, 2023 were searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Journal Database. As a result, 21 RCTs were included. The problems identified included conceptual misunderstandings regarding acupuncture direction, incomplete selection strategies, confounding research factors, and inaccuracies in reporting. Based on the findings, four strategic approaches for enhancing therapeutic efficacy through acupuncture direction were summarized: aligning needle direction with the meridian pathway, directing the needle toward the lesion site, orienting the needle toward adjacent acupoints, and targeting special anatomical structures. Two additional strategies were proposed for optimizing the procedure: simplifying acupuncture operations and directing the needle toward safe anatomical sites. Recommendations were made to improve the rationality of research factor settings and the completeness of acupuncture operation reporting. Furthermore, three methods for reporting acupuncture direction were discussed: reporting the tip-pointed position, reporting the insertion angle and orientation, and reporting azimuth and polar angles, aiming to promote greater standardization and completeness in acupuncture practice and reporting.
Acupuncture Therapy/standards* ; Humans ; Acupuncture Points ; Randomized Controlled Trials as Topic ; Meridians

Objective:To study the correlation between osteoporosis and the joint of small articular process of lumbar vertebra,and the correlation between bone mineral density(BMD)and various parameters of small joint based on quantitative computed tomography(QCT),so as to provide scientific basis for formulating clinically treatment strategies.Methods:This study included 63 patients who admitted to orthopedics of The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from December 2023 to March 2024 due to waist discomfort and lower limb pain.According to BMD standard of CT examination for lumbar vertebra,these patients were divided into normal BMD group(31 cases),osteopenia group(21 cases)and osteoporosis group(11 cases).All patients underwent CT scan on lumbar vertebra.The mode with body membrane were adopted to measure BMD,the area of left and right articular process,CT value,height after the scan was completed.Whether existed osteophytes,endplate inflammation and intervertebral disc herniation in each group were checked.Univariate Analysis of Variance(ANOVA)was employed to assess the differences among different BMD groups in age,gender,area of articular process,CT value and height.The Pathria grading system was adopted to assess the degeneration degree of intervertebral joint,and the Fisher's exact test was used to analyze the differences in degeneration scores of articular process among three groups.At the same time,the pairwise comparison between groups also was conducted.Spearman's rank correlation analysis was conducted to explore the correlation between BMD and the degeneration degree of intervertebral joint.Results:The BMD value of normal BMD group was(165.14±30.11)mg/cm3,and that of osteopenia group was(98.98±10.14)mg/cm3,and that of osteoporosis group was(58.62±18.73)mg/cm3.There was a statistically significant difference in BMD value among three groups(F=103.121,P＜0.001),and there was a statistically significant difference in BMD value between normal BMD group and osteopenia group as the result of pairwise comparison between groups(t=10.018,P＜0.001).There was statistically significant difference in BMD value between normal BMD group and osteoporosis group(t=12.989,P＜0.001),and there was statistically significant difference in BMD value between osteopenia group and osteoporosis group(t=4.641,P＜0.001).The areas of left and right upper articular process of normal BMD group were less than that of other two groups,and the differences of CT value and height of left and right upper articular process among three groups were significant(F=27.350,24.458,P＜0.05),respectively.The CT value of normal BMD group was higher than that of other two groups,and CT values of right upper articular process of osteopenia group was significantly lower than that of osteoporosis group,and the difference was statistical significance(t=2.191,P＜0.05).The heights of left and right upper articular processes of normal BMD group were lower than those of osteoporosis group,and the height of right upper articular process was lower than that of osteopenia group(t=2.331,-2.798,-2.618,P＜0.05).There was a negative correlation between osteoporosis degree and the degeneration of articular process joints(r=-0.745,P＜0.001).With the decreasing of BMD value,the degeneration of articular process joint gradually aggravated,and the ratios of osteophytes,endplate inflammation and intervertebral discs increased.Conclusion:There is a certain correlation between the osteoporosis and the degeneration of articular process joints of lumbar intervertebral disc.The ratios of osteophytes,endplate inflammation and intervertebral disc herniation increase,and both the area and height of the left and right articular process increase when the reduction of bone mass reaches to a serious degree.

Objective To study the etiology of a Chinese family with two cases of recessive non-syndromic hearing loss.Methods The clinical data of the family were collected.DNA was extracted from venous blood sam-ples,and whole-exome sequencing were performed to analyze potential causative deafness genes.Sanger sequencing was performed to verify the gene variants.Results There were 5 people among two generations in this family.The proband(Ⅱ-2,9 years old)and her brother(Ⅱ-3)had sensori-neural hearing loss,while their parents had normal hearing.The whole-exome high-throughput sequencing found that the patient carried two mutations in the CDH23 gene:c.4762C＞T(p.ARG1588TRP)and c.6604G＞A(p.ASP2202ASN).According to the American College of medical genetics and genomics(ACMG)genetic variation classification standards and guidelines,both c.6604G＞A and c.4762C＞T variants were identified as pathogenic.Conclusion The new compound heterozygous mutations c.4762C＞T and c.6604G＞A in the CDH23 gene are highly likely to be the causative factors for deafness in this family.

Objective:To study the correlation between osteoporosis and the joint of small articular process of lumbar vertebra,and the correlation between bone mineral density(BMD)and various parameters of small joint based on quantitative computed tomography(QCT),so as to provide scientific basis for formulating clinically treatment strategies.Methods:This study included 63 patients who admitted to orthopedics of The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from December 2023 to March 2024 due to waist discomfort and lower limb pain.According to BMD standard of CT examination for lumbar vertebra,these patients were divided into normal BMD group(31 cases),osteopenia group(21 cases)and osteoporosis group(11 cases).All patients underwent CT scan on lumbar vertebra.The mode with body membrane were adopted to measure BMD,the area of left and right articular process,CT value,height after the scan was completed.Whether existed osteophytes,endplate inflammation and intervertebral disc herniation in each group were checked.Univariate Analysis of Variance(ANOVA)was employed to assess the differences among different BMD groups in age,gender,area of articular process,CT value and height.The Pathria grading system was adopted to assess the degeneration degree of intervertebral joint,and the Fisher's exact test was used to analyze the differences in degeneration scores of articular process among three groups.At the same time,the pairwise comparison between groups also was conducted.Spearman's rank correlation analysis was conducted to explore the correlation between BMD and the degeneration degree of intervertebral joint.Results:The BMD value of normal BMD group was(165.14±30.11)mg/cm3,and that of osteopenia group was(98.98±10.14)mg/cm3,and that of osteoporosis group was(58.62±18.73)mg/cm3.There was a statistically significant difference in BMD value among three groups(F=103.121,P＜0.001),and there was a statistically significant difference in BMD value between normal BMD group and osteopenia group as the result of pairwise comparison between groups(t=10.018,P＜0.001).There was statistically significant difference in BMD value between normal BMD group and osteoporosis group(t=12.989,P＜0.001),and there was statistically significant difference in BMD value between osteopenia group and osteoporosis group(t=4.641,P＜0.001).The areas of left and right upper articular process of normal BMD group were less than that of other two groups,and the differences of CT value and height of left and right upper articular process among three groups were significant(F=27.350,24.458,P＜0.05),respectively.The CT value of normal BMD group was higher than that of other two groups,and CT values of right upper articular process of osteopenia group was significantly lower than that of osteoporosis group,and the difference was statistical significance(t=2.191,P＜0.05).The heights of left and right upper articular processes of normal BMD group were lower than those of osteoporosis group,and the height of right upper articular process was lower than that of osteopenia group(t=2.331,-2.798,-2.618,P＜0.05).There was a negative correlation between osteoporosis degree and the degeneration of articular process joints(r=-0.745,P＜0.001).With the decreasing of BMD value,the degeneration of articular process joint gradually aggravated,and the ratios of osteophytes,endplate inflammation and intervertebral discs increased.Conclusion:There is a certain correlation between the osteoporosis and the degeneration of articular process joints of lumbar intervertebral disc.The ratios of osteophytes,endplate inflammation and intervertebral disc herniation increase,and both the area and height of the left and right articular process increase when the reduction of bone mass reaches to a serious degree.

Objective To study the etiology of a Chinese family with two cases of recessive non-syndromic hearing loss.Methods The clinical data of the family were collected.DNA was extracted from venous blood sam-ples,and whole-exome sequencing were performed to analyze potential causative deafness genes.Sanger sequencing was performed to verify the gene variants.Results There were 5 people among two generations in this family.The proband(Ⅱ-2,9 years old)and her brother(Ⅱ-3)had sensori-neural hearing loss,while their parents had normal hearing.The whole-exome high-throughput sequencing found that the patient carried two mutations in the CDH23 gene:c.4762C＞T(p.ARG1588TRP)and c.6604G＞A(p.ASP2202ASN).According to the American College of medical genetics and genomics(ACMG)genetic variation classification standards and guidelines,both c.6604G＞A and c.4762C＞T variants were identified as pathogenic.Conclusion The new compound heterozygous mutations c.4762C＞T and c.6604G＞A in the CDH23 gene are highly likely to be the causative factors for deafness in this family.

Objective: To explore the roles of self efficacy and smoking rationalization tendency in the relationship between college students physical activity and smoking cessation beliefs, in order to provide a basis for the positive effects of college students physical activity on smoking cessation beliefs. Methods: From May 6 to 23 in 2023, 3 048 students from 10 colleges in Jiangxi Province were recruited and surveyed using the Physical Activity Participation Scale, the Smoking Cessation Self efficacy Scale, the Smoking Rationalization Tendency Scale and the Smoking Cessation Belief Scale. The Harman one way test was adopted for common method bias test. Bias correction was unfolded by Bootstrap method, and 95% confidence intervals of parameter estimates were analyzed using repeated sampling 5 000 times. Results: The results of the sequential mediation model analysis showed that physical activity was positively associated with college students beliefs about smoking cessation ( β =0.17), and physical activity, self efficacy and smoking rationalization tendency were positively associated with each other ( β =0.41, 0.08, 0.19) ( P <0.05). Both self efficacy and smoking rationalization tendency positively predicted smoking cessation beliefs ( β =0.19, 0.17, P <0.01). Self efficacy and smoking rationalization tendency mediated the relationship between physical activity and smoking cessation beliefs, with a mediating effect value of 0.09, accounting for 62.82% of the total effect value (0.15). Conclusions Self efficacy and smoking rationalization tendency have a serial mediating effect between physical activity and smoking cessation beliefs among college students. Interventions should be actively used to enhance college students beliefs about smoking cessation, promote smoking cessation behaviors.

Objective:To investigate the factors affecting postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after severe traumatic brain injury (sTBI).Methods:A case-control study was conducted to analyze the clinical data of 55 patients with prolonged disorders of consciousness after sTBI admitted to Beijing Tiantan Hospital Affiliated to Capital Medical University and Seventh Medical Center of PLA General Hospital from September 2021 to September 2022. There were 33 males and 22 females, with the age range of 13-68 years [(43.0±15.5)years]. All patients were assessed for the consciousness level using the coma recovery scale-revision (CRS-R) preoperatively and within 48 hours postoperatively. A total of 33 patients were observed in vegetative state and 22 in minimally conscious state preoperatively. The consciousness level was found to be improved in 26 patients (consciousness- improved group), but not improved in the remaining 29 patients (consciousness-unimproved group). Indicators were documented including gender, age, cause of injury, Glasgow coma score (GCS) on admission, course of injury, preoperative consciousness level, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade, analgesic regimen and sedation maintenance drugs. A univariate analysis was conducted first to assess those indicators′ correlation with postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI. Multivariate Logistic regression analysis was then used to determine the independent risk factors for their postoperative short-term improvement of consciousness level.Results:Univariate analysis showed that GCS on admission, course of injury, preoperative consciousness level and analgesic regimen were correlated with short-term improvement of postoperative consciousness level in patients with prolonged disorders of consciousness after sTBI (all P<0.05), whereas gender, age, cause of injury, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade and sedation maintenance drugs showed no relation to the improvement of postoperative consciousness level (all P>0.05). Multivariate Logistic regression analysis showed that the GCS &ge;7 points on admission ( OR=0.06, 95% CI 0.01, 0.36, P<0.01), preoperative minimally conscious state ( OR=0.09, 95% CI 0.02, 0.40, P<0.01) and intraoperative use of Sufentanil combined with Remifentanil ( OR=0.07, 95% CI 0.01, 0.43, P<0.01) were significantly correlated with postoperative improvement of consciousness level. Conclusion:The GCS on admission (&ge;7 points), preoperative minimally conscious state and intraoperative use of Sufentanil combined with Remifentanil are independent risk factors affecting short-term postoperative improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI.

[Abstract] Objective: To investigate the function and mechanism of ferroptosis in the radiation resistance of colorectal tumor-repopulating cells. Methods: Human colorectal tumor cells HCT116 (defined as Control cells) were cultured in two-dimensional normal conditions, and tumor regenerative cells with high tumorigenicity (defined as TRCs) were cultured and screened in three-dimensional fibrin soft gels by the mechanical force method. Both the control group and TRC group cells were exposed to X-rays with different doses (2, 4, 6, 8 Gy) and MTS and the clone formation assay were used tomeasure the cell viability rate and proliferation ability. After the Control cells and TRCs were treated with ferroptosis inducer (Erastin) and X-rays respectively, they were stained with C11-BODIPY reagent, and the lipid peroxidation level of the cells was observed and determined by confocal microscopy and flow cytometry. qPCR was used to determine the effects of Erastin and X-rays treatments on the expressions of ferroptosis-related genes glutathione peroxidase 4 (GPX4) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) in the Control cells and TRCs; WB assay was performed to determine the effects on the expressions of ferroptosis-related proteins GPX4 and ACSL4. Results: Colorectal TRCs with high stemness were cultured and screened out from soft fibrin gels. After irradiation with different doses (2, 4, 6, 8 Gy) of X-rays, the viability rate, the clone sizeand the number of clones in the control group were significantly lower than those in the TRC group (all P<0.05). After the cells in the control group were irradiated with different doses of X-rays (4, 8 Gy) and treated with Erastin, the lipid peroxidation level of the cells in the X-ray treated group was significantly higher than that in the untreated group (P<0.05). The lipid peroxidation level of the cells in the Erastin-treated group was significantly higher than that in the DMSO-treated group (P<0.05). There was no statistical difference among all treatment subgroups in the TRC group (all P>0.05). The mechanism study indicated that compared with those in control cells, GPX4 and ACSL4 in TRCs under ferroptosis-inducing conditions (X-ray radiation and Erastin treatment) presented expressions that contributed more to radiation resistance, i.e., continued upregulation of GPX4 and downregulation of ACSL4 and their expressions were dependent on the doses of Erastin. Conclusion: Colorectal TRCs may resist ferroptosis through a high expression of GPX4 and a low expression of ACSL4, which in turn induces radiation resistance.