Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To compare the clinical efficacy between robot-assisted and free-hand percutaneous cannulated screwing (PCS) in the treatment of femoral neck fractures in the middle-aged and young patients.Methods:A retrospective study was conducted to analyze the clinical data of 53 patients with femoral neck fracture who had been treated with PCS from May 2020 to May 2022 at Department of Traumatic Surgery, Maoming Hospital Affiliated to Southern Medical University. In the robot group of 25 patients subjected to robot-assisted PCS, there were 11 males and 14 females with an age of (48.2 ± 11.9) years; in the free-hand group of 28 patients subjected to free-hand PCS, there were 13 males and 15 females with an age of (48.5 ± 9.8) years. The 2 groups were compared in terms of operation time, intraoperative bleeding, intraoperative guide drills, intraoperative fluoroscopy frequency, fracture union time, Harris hip score at the last follow-up and postoperative complications. Postoperative imaging examination was performed to evaluate distribution accuracy of the cannulated screws in the femoral neck (deviation between the screws and the femoral neck axis, parallelism between the screws and distance between the screws and the neck cortex).Results:There was no statistically significant difference between the robot and free-hand groups in the general clinical data before operation, showing comparability ( P>0.05). The robot group showed significantly shorter operation time [(32.7 ± 4.8) min], significantly less intraoperative bleeding [(14.6 ± 4.8) mL], significantly less intraoperative guide drillings [(3.5 ± 0.7) times] and significantly less intraoperative fluoroscopy frequency [(7.9 ± 1.4) times] than the free-hand group [(56.9 ± 11.3) min, (27.0 ± 7.3) mL, (9.1 ± 1.8) times and (16.3 ± 6.0) times)] (all P<0.05). Postoperative imaging showed that the deviation between the screws and the femoral neck axis was 4.4° ± 1.1° on the anteroposterior X-ray film and 3.2° ± 0.8° on the lateral X-ray film, the parallelism between the screws 4.9° ± 0.8° on the anteroposterior X-ray film and 3.0° ± 0.7° on the lateral X-ray film, and the distance between the screws and the femoral neck cortex (10.4 ± 2.7) mm in the robot group, all significantly smaller than those in the free-hand group [10.5° ± 2.8°, 4.9° ± 1.1°, 12.1° ± 4.0°, 5.1° ± 1.3°, and (15.4 ± 3.2) mm] (all P<0.05). All the 53 patients were followed up for (22.2 ± 8.5) months. All fractures got united. The fracture union time in the robot group [(20.6 ± 4.6) weeks] was insignificantly shorter than that in the free-hand group [(23.7 ± 7.7) weeks] ( P>0.05). At the last follow-up, the Harris hip score in the robot group [(88.6 ± 5.6) points] was significantly higher than that in the free-hand group [(84.8 ± 6.3) points] ( P<0.05). Follow-ups revealed 2 cases of internal fixation loosening, 1 case of screw head cutting and 1 case of femoral head necrosis in the free-hand group but none of such complications in the robot group. Conclusion:In the treatment of femoral neck fractures in the middle-aged and young patients, compared with free-hand PCS, robot-assisted PCS shows advantages of shorter intraoperative time, less bleeding, less fluoroscopic radiation, higher accuracy of screw placement, a lower incidence of postoperative complications and better functional recovery of the hip joint.

Objective:To explore the surgical techniques and outcomes of closed reduction for geriatric subtrochanteric femoral fractures with certain radiological characteristics.Methods:A retrospective analysis was conducted in the 38 aged patients with subtrochanteric femoral fracture who had been treated at Department of Geriatric Orthopedics, Guangdong Provincial Hospital of Chinese Medicine from January 2015 to December 2019. There were 24 females and 14 males, aged from 62 to 95 years (average, 80.9 years). According to the Seinsheimer classification, there were one case of type ⅡB, 7 cases of type ⅡC, 18 cases of type ⅢA, 9 cases of type Ⅳ, and 3 cases of type Ⅴ. The time from injury to operation averaged 2.3 days (from 0.5 to 8.0 days). The fractures of this cohort were characterized by: ①The starting point of the medial fracture line was at the proximal end and the lesser trochanter separated. ②The fracture end was shortened and overlapped on the medial side and angled outward, showing a varus deformity. ③The alignment returned to normal after traction, with only partial lateral displacement left. Before fixation with proximal femoral nail antirotation (PFNA), all these patients were treated by closed reduction in a supine traction bed. In those whose reduction was unsatisfactory, a main nail was inserted or after the main nail was inserted reduction by leverage was performed through the screw blade incision. Intraoperatively, the quality of fracture reduction was evaluated according to the modified Baumgaertner assessment. Recorded were the patients’ operation time, intraoperative blood loss, fracture healing time, hip function and complications.Results:All the fractures achieved 100% of good to excellent reduction (38/38). The operation time ranged from 25 to 120 min (average, 55.6 min) and the intraoperative blood loss from 10 to 150 mL (average, 42.9 mL). This cohort of 38 patients was followed for 10 to 20 months (average, 15.3 months). All the fractures united after 3 to 8 months (average, 4.8 months). The Harris hip scores at the last follow-up ranged from 70 to 94 (average, 81.5). The follow-ups revealed no such complications as internal fixation failure, fracture re-displacement, malunion or nonunion.Conclusion:Closed reduction and PFNA fixation in a supine traction bed can lead to satisfactory clinical effects for the subtrochanteric femoral fractures with certain radiological characteristics in the aged patients.

Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2＝ 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2＝0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.

Objective To compare the effects of ticagrelor and clopidogrel on platelet aggregation rate, myocardial perfusion and prognosis in patients with acute myocardial infarction. Methods One hundred and sixty-nine patients with acute ST segment elevation myocardial infarction (STEMI) and emergency percutaneous coronary intervention (PCI) were recruited and randomly divided into ticagrelor group (85 cases) and clopidogrel group (84 cases). The TIMI blood flow before and after PCI was recorded, and the ST segment fall rate of 1 h ECG after PCI was calculated. The platelet aggregation rate was measured. After 12 months' follow-up, the incidence of major adverse cardiac events (MACE) was recorded. The Logistic regression analysis was used to discover the factors of MACE. Results One hundred and sixty-nine patients with acute STEMI were recruited including 85 cases treated with ticagrelor and 84 cases in clopidogrel group. The ECG ST segment fall rate after PCI in ticagrelor group was significantly higher than that in clopidogrel group: (61.3 ± 30.7)％ vs. (47.8 ± 26.6)％, P<0.05. The platelet aggregation rate 2 h, 24 h and 7 d after PCI in ticagrelor group was significantly lower than that in clopidogrel group (P<0.05). MACE occurred in 19 cases (22.4％) in ticagrelor group and in 21 cases (25.0％) in clopidogrel group, and there was no significant difference (P > 0.05). Multiple Logistic regression analysis revealed that age and ECG ST segment fall rate were independent risk factors for MACE (P<0.05). Conclusions Compared with clopidogrel, ticagrelor can effectively reduce platelet aggregation rate and accelerate ST segment fall in STEMI patients, but their long-term prognosis is similar.

Objective To investigate the predictive value of serum adiponectin level on morbidity of acute myocardial infarction, and to evaluate its impact on prognosis in patients with acute myocardial infarction after percutaneous coronary intervention (PCI). Methods We prospectively recruited patients with acute ST segment elevation myocardial infarction (STEMI) who had underwent primary PCI. Their serum adiponectin levels were measured. The TIMI blood flow classification of culprit vessel was recorded after PCI. Echocardiography was performed in 24 h after PCI to evaluate left ventricular ejection fraction (LVEF). Major adverse cardiac events (MACE) were recorded including cardiac death, recurrent nonfatal myocardial infarction, target vessel reascularization, and readmission for heart failure after 18 months′ followed-up. Results 108 consecutive patients with STEMI and 38 control patients without coronary artery stenosis were recruited. The serum adiponectin level in STEMI group was significantly lower than that in control: (1 413.9 ± 218.8) ng/L vs.(1 756.3 ± 205.5) ng/L (P<0.01). STEMI patients with LVEF < 50% had lower serum adiponectin level compared with LVEF ≥50%: (1 334.1 ± 226.3) ng/L vs. (1 453.0 ± 213.8) ng/L , P<0.01. The serum adiponectin level in the TIMI 0-2 group after PCI was significantly lower than that in the TIMI 3 group:(1 350.7 ± 214.9) ng/L vs. (1 430.6 ± 218.5) ng/L, P < 0.01. Multiple logistic regression analysis revealed that lower serum adiponectin level was an independent predictor of STEMI ( OR=0.992, 95% CI 0.987-0.996, P<0.01). MACE occurred in 22 patients (20.4% ). Cox regression analysis revealed that lower serum adiponectin level remained an independent predictor of MACE ( OR=0.996, 95% CI 0.993-0.999, P < 0.01). Conclusions Lower serum adiponectin level is significantly associated with morbidity of STEMI and adverse prognosis in patients with acute myocardial infarction.

OBJECTIVE To investigate the cytotoxicity of cyflumetofen for SH-SY5Y cells and the mechanism. METHODS SH-SY5Y cells treated with cyflumetofen 0.03, 0.06, 0.125, 0.25, 0.5, 1, 2, 2.6, 4, 6, 8 and 16 mmol·L-1 for 48 h. Cell survival was measured with MTT assay. The reactive oxygen species (ROS) was determined with the DCFH- DA probe, and mitochondrial membrane potential (MMP) was detected by JC-1 staining. The morphological changes in cell nuclei were observed with Hoechst33258 staining. Cell cycle and apoptosis were determined by flow cytometry. The protein levels of phosphorylated Jun Kinase (p-JNK) and p-P38 were measured by Western blotting. RESULTS Compared with solvent (DMSO) control group, cyflumetofen (≥0.06 mmol · L- 1) inhibited the proliferation of SH- SY5Y cells obviously (P<0.05), and the IC50 was 2.6 mmol·L-1. MMP declined and ROS levels increased significantly in cyflumetofen 1, 2, 4 and 6 mmol·L- 1 groups (P<0.01). Cyflumetofen 2, 4 and 6 mmol·L- 1 induced nucleic accumulation, nuclear shrinkage and disintegration in SH-SY5Y cells. Apoptosis rates of cyflu? metofen 2, 4 and 6 mmol·L- 1 groups increased from (0.7±0.1)% in DMSO control group to (6.7±0.1)%, (72.4±8.6)% and (90.7±3.2)% (P<0.01). Cyflumetofen 4 and 6 mmol·L- 1 induced G1 phase cell cycle arrest (P<0.01). In addition, Western blotting showed that cyflumetofen 4 and 6 mmol·L-1 up-regulated the expression of p-JNK (P<0.01), while the level of p-P38 in SH-SY5Y cells was increased in cyflumetofen 6 mmol · L- 1 group (P<0.01). CONCLUSION Cyflumetofen induces cell damage, apoptosis and G1 phase cell cycle arrest in SH- SY5Y cells. The mechanism may be associated with oxidative damage, and activation of P38 and JNK stress-response pathways.

Objective:To characterize the clinical and epidemiological changes, treatments, and prognoses of primary esophageal small cell carcinoma (PESC). Methods:A retrospective analysis was conducted using the clinical epidemiology data of 529 PESC patients se-lected from the clinical databases of 500,000 esophageal and gastric cardiac carcinomas of the Henan Key Laboratory for Esophageal Cancer Research (1992-2015). Among these patients, 241 cases were included in the survival analysis. The five-year survival rate was calculated using Kaplan-Meier analysis, and the differences in survival rates were compared using the Log-rank analysis model. Re-sults:All 529 PESC cases were analyzed, which accounted for 0.2%of esophageal cancers diagnosed in the same period. The incidence of PESC increased annually (R2=0.574). The survival rates for 1-, 2-, 3-, and 5-year of 241 PESC patients were 55%, 40%, 29%, and 9%, respectively, and the median survival time was 21.9 months. On the basis of the VALSG criteria of lung small cell carcinoma, a statisti-cal difference was observed in the overall survival rates for limited and extensive diseases (P=0.003), with the median survival time of 24.3 and 17.5 months, respectively. Furthermore, significant differences were observed on survival with various treatment modalities (P=0.004). The median survival time of PESC patients treated with combined surgery and radiochemotherapies (28.8 months) was lon-ger than those with either chemotherapy (17.8 months, P=0.015) or chemoradiotherapy (14.5 months, P=0.004). In limited disease pa-tients, the median survival time was longer in patients treated with surgery (27.7 months) than in those without surgery (16.2 months, P=0.007). Notably, the biopsy diagnosis before surgery for PESC was only 40.8%. Conclusion:PESC is a rare malignant carcinoma with increasing incidence. PESC presents poor prognosis, and the survival rate can be improved through combined therapies based on sur-gery. A high misdiagnosis rate for PESC is observed before surgery with biopsy.

Objective To detect the expression of beta 2 adrenergic receptor in the infantile hemangiomas (IH) tissue and to explore its role in the pathological evolution of infantile hemangiomas as well.Methods 48 cases of infantile hemangioma were divided into two groups.29 cases were in the proliferating period,while the other 19 cases were in non-proliferating period.By using immunofluorescence technology,the endothelial nuclei and beta 2 adrenergic receptor of the IH tissue were marked by fluorescent tags,respectively,in two groups.The location of fluorescent labeling was shown in photos.By using the Image-Pro Plus 6.0 software,we analyzed and compared the average fluorescence intensity of endothelial cell nucleus and beta 2 adrenergic receptors in these two groups.Results Beta 2 adrenergic receptors were widely expressed in IH tissue,especially in endothelial cell nucleus shown in fluorescent images.The average fluorescence intensity of endothelial cell core in proliferating IH group was 0.031 ±0.002,which was much higher than that of fading period IH group (0.022±0.002).There was significant statistical different (P＜0.05).The average fluorescence intensity of beta 2 adrenergic receptor in proliferating IH group was 0.035± 0.003,which was much higher than that of fading period IH group (0.028± 0.002).There was significantly statistical different between the two groups (P＜0.05).Conclusions Beta 2 receptors are widely expressed in the endothelial cells of infantile hemangioma.