BACKGROUND:Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering.The efficiency of traditional two-dimensional culture for hepatocyte induction is low,and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.OBJECTIVE:To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells,focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation,providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.METHODS:Relevant articles in the PubMed and other databases such as CNKI were searched,using Chinese and English search terms"mesenchymal stem cell,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics."Additionally,the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.RESULTS AND CONCLUSION:(1)Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids,biological scaffolds,bioprinting,and microfluidic chips.Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation.(2)During the differentiation of mesenchymal stem cells into hepatocyte-like cells,epigenetic regulation plays a key role,primarily involving histone modification,DNA methylation,and the regulation of non-coding RNAs.(3)Under three-dimensional culture conditions,epigenetic modifications,especially histone acetylation,play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

Objective:To explore the predictive role of dynamic changes in serum Golgi protein 73 (GP73) and its inflammatory influencing factors on the reversal of hepatitis B virus-related liver fibrosis.Methods:Two hundred and seventy-eight patients with hepatitis B virus-related liver fibrosis who received entecavir or combined Fuzheng Huayu tablets treatment and completed two liver biopsies (biopsy) in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2014 to July 2019 were selected. The correlation between serum GP73 level and fibrosis stage (Ishak) and inflammation grade (HAI) was analyzed. The patients were divided into a fibrosis reversal group (Ishak decreased≥1 point) and a non-reversal group (Ishak score remained unchanged or increased), and an inflammation improvement group (ΔHAI≤-2) and a non-improvement group (ΔHAI>-2) according to the pathological changes of liver tissue before and after treatment. The cross-sectional value of GP73, its change value (ΔGP73), and the role of inflammatory influencing factors on the liver before and after treatment were evaluated for their predictive efficacy regarding liver fibrosis regression. The receiver operating characteristic curve was used to explore the predictive value of serum ΔGP73 combined with liver stiffness change value (ΔLSM) for the reversal of hepatitis B virus-related liver fibrosis. One-way analysis of variance was used to compare the data between the groups of quantitative data, and a paired t-test or rank sum test was used for the data before and after treatment. The χ2 test was used to compare the differences between the groups of enumeration data. Spearman and Pearson correlation methods were used for correlation analysis. Results:The serum GP73 level was higher in the cirrhosis group than that in the group without significant fibrosis ( P<0.01). The GP73 level was higher in patients with moderate and severe inflammation than that in the mild group ( P<0.05). Pre-treatment serum GP73 was positively correlated with fibrosis stage ( r=0.248), inflammation grade ( r=0.318), and alanine aminotransferase level ( r=0.203) ( P<0.01). The area under the receiver operating characteristic curve (AUROC) for the predictive ability of post-treatment GP73 levels in the fibrosis reversal was 0.633 (95% CI: 0.573-0.689, sensitivity 62.68%, and specificity 59.56%). The decrease in ΔGP73 was significantly higher in the liver fibrosis reversal group ( n=142) than that in the non-reversal group ( n=136) [-39.22(-85.08,-14.31) ng/mL vs. -30.06(-61.29,-5.84) ng/mL, P<0.01]. ΔGP73 was also associated with liver inflammation changes (AUROC=0.634, 95% CI: 0.574-0.690, sensitivity of 51.64%, specificity of 69.87%). Additionally, the predictive effectiveness of GP73 for fibrosis reversal improved after normalization of serum ALT (AUROC: 0.651 vs. 0.522 at baseline). ΔGP73 combined with ΔLSM had improved the AUROC predictive effectiveness from single indicators of 0.609 (ΔGP73) and 0.656 (ΔLSM) to 0.800 (95% CI: 0.662-0.899), with specificity increasing from 72.22% to 86.11%. Conclusion:Serum GP73 level is positively correlated with the degree of liver fibrosis and inflammation. Serum GP73 levels and ΔGP73 can predict the reversal of fibrosis, with liver inflammation being an important influencing factor following treatment. ΔGP73 combined with ΔLSM can significantly optimize the evaluation efficiency of liver fibrosis reversal.

BACKGROUND:Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering.The efficiency of traditional two-dimensional culture for hepatocyte induction is low,and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.OBJECTIVE:To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells,focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation,providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.METHODS:Relevant articles in the PubMed and other databases such as CNKI were searched,using Chinese and English search terms"mesenchymal stem cell,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics."Additionally,the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.RESULTS AND CONCLUSION:(1)Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids,biological scaffolds,bioprinting,and microfluidic chips.Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation.(2)During the differentiation of mesenchymal stem cells into hepatocyte-like cells,epigenetic regulation plays a key role,primarily involving histone modification,DNA methylation,and the regulation of non-coding RNAs.(3)Under three-dimensional culture conditions,epigenetic modifications,especially histone acetylation,play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

Objective:To explore the predictive role of dynamic changes in serum Golgi protein 73 (GP73) and its inflammatory influencing factors on the reversal of hepatitis B virus-related liver fibrosis.Methods:Two hundred and seventy-eight patients with hepatitis B virus-related liver fibrosis who received entecavir or combined Fuzheng Huayu tablets treatment and completed two liver biopsies (biopsy) in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2014 to July 2019 were selected. The correlation between serum GP73 level and fibrosis stage (Ishak) and inflammation grade (HAI) was analyzed. The patients were divided into a fibrosis reversal group (Ishak decreased≥1 point) and a non-reversal group (Ishak score remained unchanged or increased), and an inflammation improvement group (ΔHAI≤-2) and a non-improvement group (ΔHAI>-2) according to the pathological changes of liver tissue before and after treatment. The cross-sectional value of GP73, its change value (ΔGP73), and the role of inflammatory influencing factors on the liver before and after treatment were evaluated for their predictive efficacy regarding liver fibrosis regression. The receiver operating characteristic curve was used to explore the predictive value of serum ΔGP73 combined with liver stiffness change value (ΔLSM) for the reversal of hepatitis B virus-related liver fibrosis. One-way analysis of variance was used to compare the data between the groups of quantitative data, and a paired t-test or rank sum test was used for the data before and after treatment. The χ2 test was used to compare the differences between the groups of enumeration data. Spearman and Pearson correlation methods were used for correlation analysis. Results:The serum GP73 level was higher in the cirrhosis group than that in the group without significant fibrosis ( P<0.01). The GP73 level was higher in patients with moderate and severe inflammation than that in the mild group ( P<0.05). Pre-treatment serum GP73 was positively correlated with fibrosis stage ( r=0.248), inflammation grade ( r=0.318), and alanine aminotransferase level ( r=0.203) ( P<0.01). The area under the receiver operating characteristic curve (AUROC) for the predictive ability of post-treatment GP73 levels in the fibrosis reversal was 0.633 (95% CI: 0.573-0.689, sensitivity 62.68%, and specificity 59.56%). The decrease in ΔGP73 was significantly higher in the liver fibrosis reversal group ( n=142) than that in the non-reversal group ( n=136) [-39.22(-85.08,-14.31) ng/mL vs. -30.06(-61.29,-5.84) ng/mL, P<0.01]. ΔGP73 was also associated with liver inflammation changes (AUROC=0.634, 95% CI: 0.574-0.690, sensitivity of 51.64%, specificity of 69.87%). Additionally, the predictive effectiveness of GP73 for fibrosis reversal improved after normalization of serum ALT (AUROC: 0.651 vs. 0.522 at baseline). ΔGP73 combined with ΔLSM had improved the AUROC predictive effectiveness from single indicators of 0.609 (ΔGP73) and 0.656 (ΔLSM) to 0.800 (95% CI: 0.662-0.899), with specificity increasing from 72.22% to 86.11%. Conclusion:Serum GP73 level is positively correlated with the degree of liver fibrosis and inflammation. Serum GP73 levels and ΔGP73 can predict the reversal of fibrosis, with liver inflammation being an important influencing factor following treatment. ΔGP73 combined with ΔLSM can significantly optimize the evaluation efficiency of liver fibrosis reversal.

Objective:To explore the effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with severe wrist electric burn.Methods:A retrospective observational study was conducted. From January 2017 to December 2020, 4 patients with wrist high-voltage electric burn admitted to the Department of Burns of the First People's Hospital of Zhengzhou and 4 patients with wrist high-voltage electric burn admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital met the inclusion criteria, including 6 males and 2 females, aged 12 to 52 years. They were all classified as type Ⅱ wrist high-voltage electric burns with median nerve defect. In the first stage, the wounds were repaired with free anterolateral thigh femoral myocutaneous flap. In the second stage, the free gracilis muscle flap combined with sural nerve transplantation was used to reconstruct the digital flexion and sensory function of the affected hand in 3 to 6 months after wound healing. The cut lengths of muscle flap and nerve were 32 to 38 and 28 to 36 cm, respectively. The muscle flap donor area and nerve donor area were both closed and sutured. The survival condition of gracilis muscle flap and sural nerve, the wound healing time of recipient area on forearm, the healing time of suture in muscle flap donor area and nerve donor area were observed and recorded after operation, and the recovery of donor and recipient areas was followed up. In 2 years after operation, the muscle strength of thumb and digital flexion and finger sensory function after the hand function reconstruction were evaluated with the evaluation criteria of the hand tendon and nerve repair in the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association.Results:All the gracilis muscle flap and sural nerve survived successfully after operation. The wound healing time of recipient area on forearm was 10 to 14 days after operation, and the healing time of suture in muscle flap donor area and nerve donor area was 12 to 15 days after operation. The donor and recipient areas recovered well. In the follow-up of 2 years after operation, the muscle strength of thumb and digital flexion was evaluated as follows: 4 cases of grade 5, 3 cases of grade 4, and 1 case of grade 2; the finger sensory function was evaluated as follows: 4 cases of grade S3 +, 2 cases of grade S3, and 2 cases of grade S2. Conclusions:For patients with hand dysfunction caused by severe wrist electric burn, free gracilis muscle flap combined with sural nerve transplantation can be used to reconstruct the digital flexion and sensory function of the affected hand. It is a good repair method, which does not cause great damage to thigh muscle flap donor area or calf nerve donor area.

Objective:To explore the curative effects of ultrathin anterolateral femoral flap in one-stage split-finger repair of palmar combined with multiple finger wounds.Methods:A retrospective observational study was conducted. From October 2016 to June 2018, 20 patients with wounds on palms and multiple fingers who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 15 males and 5 females, aged 18 to 77 years. After debridement, the wound area was 8 cm×4 cm-17 cm×12 cm. The wound was repaired by ultrathin anterolateral femoral flap with area of 9 cm×5 cm to 19 cm×13 cm. According to the wound condition of finger, the finger division was performed in one stage, and the length-to-width ratio of the split-finger flap was 2.0:1.0-2.5:1.0. During the surgery, the descending branches of lateral circumflex femoral artery and accompanying vein of flap were anastomosed end-to-end to the radial artery and vein in the recipient area, respectively, and the anterolateral femoral cutaneous nerve of flap was bridged with the superficial branch of radial nerve in the recipient area. The wounds in the donor area of flap in 14 patients were sutured directly, the wounds in the donor area of flap in 3 patients were repaired by relay superficial iliac circumflex artery perforator flap, and the wounds in the donor area of flap in 3 patients were covered by free trunk medium-thick skin graft. The survival of flap, occurrence of vascular crisis and other complications, and healing of wounds in the donor area of flap were recorded. The appearance of flap, scar hyperplasia in the donor and recipient areas and the patients' satisfaction with the shape and function of the donor and recipient areas were followed up. In 1 year after surgery, the two-point discrimination distance of the flap was measured, and the recovery of hand function was evaluated by the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association.Results:The flaps of 17 patients survived without vascular crisis or other complications after surgery. The flap of 1 patient had poor blood circulation and partial necrosis, and the wound was healed 14 days after dressing change and grafting of split-thickness skin graft from head. Two patients had mild cyanosis at the margin of flap after surgery, which disappeared spontaneously 5 days later. Incisions at donor site, relay flaps, and skin grafts of all patients survived well. After surgery, the color and texture of flap were basically the same as that of the normal skin of hand, and linear scars were observed in the donor and recipient areas. The patients were satisfied with the recovery of appearance and function of donor and recipient areas. After 1 year of follow-up, the patients' hand sensory function recovered well, the two-point discrimination distance of flap was 4-6 mm, and the recovery of hand function was evaluated as excellent in 18 cases and good in 2 cases.Conclusions:The ultrathin anterolateral femoral flap in repairing the palmar combined with multiple finger wounds in one-stage split-finger can significantly reduce the number of surgeries and improve the function and beauty of the hand, so it is worthy of clinical promotion.

OBJECTIVE：To investigate the effects of parecoxib sodium ，flurbiprofen axetil and lornoxicam combined with patient controlled intravenous analgesia （PICA） on postoperative analgesia in patients undergoing gynecological laparoscopic surgery and its effect on serum related factors. METHODS ：A total of 280 patients who underwent gynecologic laparoscopic surgery in the Second Affiliated Hospital of Hainan Medical University from Mar. 2017 to Mar. 2019 were randomly divided into control group （group C ），parecoxib sodium group （group P ），and flurbiprofen axetil group （group F ）and lornoxicam group （group L ）acording to random number table ，with 70 patients in each group. Four groups of patients received Sodium chloride injection 5 mL，Parecoxib sodium for injection 40 mg，Flurbiprofen axetil injection 50 mg and Lornoxicam for injection 8 mg （added 8 mg when the effect was not good ）intravenously at 30 min before the end of surgery. At the end of surgery ，they were given PICA of Sufentanil citrate injection and Dizosin injection for analgesia. The situation of pain and nausea symptom were evaluated at 6，12，24 and 48 h after surgery by using numerical rating scale （NRS）. The levels of serum CRP ，IL-6，SP and PGE 2 were detected by chemiluminescence method and ELISA. The times of pressing PICA pump and the dosage of analgesic were recorded in 4 groups within 24 h after surgery. The ADRs of patients within 48 h after surgery were recorded ，such as bloating ， dizziness，itchy skin ，respiratory depression and urinary retention. RESULTS ：At different time points ，the NRS scores of pain of group P ，F and L were significantly lower than those of group C ；and 48 h after surgery ，NRS score of pain of group L was significantly lower than those of group P and F （P＜0.05）. There was no statistical significance in the level of CRP ，IL-6，SP and PGE2 of 4 groups before surger （P＞0.05）. The CRP ，IL-6，SP and PGE 2 levels at each time point after surgery of group P ，F and L were significantly lower than those of group C ；compared with group P ，serum level of SP at 48 h after surgery as well as serum levels of PGE 2 at 12，24 and 48 h after surgery were significantly decreased in group F ，and serum level of IL- 6 at 48 h after surgery，serum levels of SP at 24 and 48 h after surgery ，serum levels of PGE 2 at 12，24，48 h after surgery were decreased significantly in group L ；compared with group F ，serum level of SP at 48 h after surgery as well as serum levels of PGE 2 at 12， 24，48 h after surgery were all decreased significantly in group L （P＜0.05）. There was no statistical significance in the incidence of anausea and vomiting among 4 groups（P＞0.05）. CONCLUSIONS ：Parecoxib sodium ，flurbiprofen axetil and lornoxicam combined with PICA can effectively relieve the pain of patients after gynecological laparoscopic surgery and reduce the levels of serum related factor ，and lornoxicam has the most obvious effect.

In the information era, Internet has become the main channel for health and family planning net-work opinion for the public health monitoring. This paper outlines the general situation of the public opinion of online health and family planning based on the monitoring analysis conducted in 2015 . It also studies the characteristics of the aforesaid public opinion, and analyzes and evaluates the focus of the public opinion of hygiene and family plan-ning. Based on this, further suggestions on the promotion of health and family planning were put forward.