Portal vein tumor thrombus (PVTT) is one of the common complications of hepatocellular carcinoma (HCC) with a high mortality rate. Several studies have shown that active implementation of effective treatment can significantly improve the quality of life and prolong survival of HCC patients with PVTT. In recent years, with the continuous development of molecular biology and molecular immunology, the treatment of advanced liver cancer has shifted from single agent to combination therapy, among which, the combination of immune checkpoint inhibitors and other systemic or local therapies has attracted much attention. This treatment strategy has shown good efficacy in some large-scale clinical trials. With the deepening of relevant research, it is believed that this treatment scheme will bring more hope and opportunities to such patients.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

Objective:To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure.Methods:Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 μg/m 3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results:After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group ( P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1β, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion:UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

Objective:To investigate the effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway.Methods:A total of 160 male Wistar rats were randomly divided into blank non-intervention, blank intervention, arthritis non- intervention and arthritis intervention groups with 40 rats in each group. Rats in the arthritis groups were subjected to unilateral anterior cruciate ligament transection, while rats in the blank groups were only subjected to skin incision and suture. Rats in the intervention groups were treated by intra-articular injection of 1 mL 10 μmol/L licochalcone A for 8 successive weeks. Eight weeks later, the cartilage of rats in each group was stained with safranin, and osteoarthritis soft tissue was scored according to Osteoarthritis Research Society International guideline under the optical microscope. The cartilage was cultured in low glucose cell culture medium supplemented with 5% fetal bovine serum for 48 hours. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan and collagen II in the medium were determined by the chemiluminescence reaction method. The expression levels of p38, phosphorylated p38 (p-p38) and matrix metalloproteinase in cartilage tissue were detected by western blot assay. Results:The progress of osteoarthritis in rats treated with licochalcone A was slow. The Osteoarthritis Research Society International score in the arthritis intervention group was significantly lower than that in the arthritis non-intervention group [(3.8 ± 1.7) points vs. (9.7 ± 1.2) points, P = 0.0064]. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan, and collagen II in the arthritis intervention group were (77.84 ± 17.65) μmol/mg and (6.78 ± 1.76) ng/mg, (89.78 ± 9.76) μg/mg, and (1.78 ± 0.76) μg/mg, respectively, which were significantly lower than those in the arthritis non-intervention group [(107.56 ± 18.74) μmol/mg, (10.756 ± 1.87) ng/mg, (125.75 ± 8.87) μg/mg, (3.76 ± 0.88) μg/mg, (NO: P = 0.002; PGE 2: P < 0.001; sGAG: P < 0.001; Collagen II: P < 0.001). Western blot assay results revealed that the relative expression of p38, p-p38, p-p38 to total p38 ratio, matrix metalloproteinase in the arthritis intervention group were (3 454 ± 421), (2 072 ± 175), (0.65 ± 0.14 )and (1 776 ± 765), respectively, which were significantly lower than those in the arthritis non-intervention group (5 322 ± 323), (4 257 ± 184), (0.89 ± 0.11), (3 865 ± 874)( p38: P < 0.001; p-p38: P < 0.001; p-p38/p38: P = 0.002; MMP: P = 0.001). Conclusion:Licochalcone A can delay the progression of osteoarthritis in rats with osteoarthritis through inhibiting inflammatory reaction and cartilage matrix degradation, and p38-MAPK signaling pathway may be involved in the regulation process.

Objective:To study the clinical manifestations and prognosis of patients with liver perivascular epithelioid cell tumor (PEComa).Methods:The clinical manifestations, imaging findings, pathological features, treatment and prognosis of 17 patients with liver PEComa managed in Shenzhen People's Hospital from September 2002 to January 2020 were retrospectively analysed.Results:The patient age of onset of liver PEComa was 22 to 54 years (average 34.8 years). There were 13 females and 4 males. 82%(14/17) of patients presented with no significant symptoms. 15/17 had solitary tumors. The diagnostic rate using preoperative B-ultrasound, CT and MRI was low. Postoperative pathological studies showed the tumor cells were mainly epithelioid cells with hyaline or eosinophilic cytoplasm. There were abundant blood vessels in the tumor tissues. Adipose tissues were also seen. Immunohistochemistry showed both HMB45 and Melan-A positivities to arrive at the diagnosis. All patients were treated with surgical resection. There were no recurrence, metastasis, or death on follow-up.Conclusion:Hepatic PEComa occurred more frequently in young women and it had no specific clinical manifestations. Except for a small number of tumors with adipose tissue detected on preoperative imagings, this tumor was difficult to diagnose, or even be suspected on preoperative imagings. Pathological examination combined with immunohistochemistry after surgery established the diagnosis. Surgery resulted in good prognosis.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.

Objective To investigate prospectively the changes of quantitative parameters in dynamic contrast-enhanced MRI (DCE-MRI) in cervical cancer patients before and after neoadjuvant chemotherapy (NACT).Methods Thirty-eight patients with locally advanced cervical cancer (in stage Ⅰ B2,Ⅱ A2,Ⅱ B) underwent DCE-MRI one week before and 1 month after NACT.The patients were classified into two groups:significant reaction(sCR) group and non-sCR group.The DCE-MRI pharmacokinetics parameters (mean Ktrans,mean Kep,mean Ve and mean Vp) were measured and compared between the sCR and non-sCR groups.Receiver operating characteristic (ROC) curves were constructed to describe the diagnostic accuracy of the significant parameters and their decision thresholds.Results There were 22 and 16 patients in sCR and non-sCR groups,respectively.Before NACT,the mean Ktrans was higher (P＜0.05) but the mean Ve (P＜0.05) was lower in sCR group than those in non-sCR group,and these differences were statistically significant,respectively.After NACT,the mean Ktrans (P＜0.05) and the changed value of Ktrans (P＜0.05) were significantly lower in the sCR group compared with those in the non-sCR group.The remained parameters such as Vp and Kep had no statistically difference between the two groups.When combined the parameters values before and after treatment by using ROC curves,the area under curve (AUC) of pre-mean Ktrans and /Ktrans were 0.801 (P＜0.05),0.955 (P＜0.001).The optimal cut off value for distinguishing sCR from non-sCR were the pretreatment Ktrans (0.702 0) and/Ktrans (0.043 7),and their sensitivity and specificity were 77.3％,81.2 ％,95.5％ and 81.2％,respectively.Conclusion Quantitative parameters of DCE-MRI provided a new noninvasive way to reflect the changes of hemodynamics in cervical cancer patients with NACT.The quantitative parameters,such as pre-mean Ktrans and /Ktrans could predict the treatment efficacy more precisely.

Objective To investigate the role of autophagy in the development of diabetic cataract by detecting the expression of autophagy-related factors (BECN1,LC3B,P62) in diabetic mouse lens epithelial cells.Methods Eighty C57BL/6 male mice were selected.Fifty C57 mice were consecutively dosed with streptozotocin (STZ) 50 mg/ (kg · d) by intraperitoneal injection to induce type 1 diabetes mellitus model,and served as the model group;the remaining 30 mice were injected with appropriate dose of citrate buffer,and served as the control group.The fasting plasma glucose was tested by collecting the caudal vein blood in the model group.The morphological changes of autophagy of lens epithelial cells were observed by transmission electron microscopy.The expression and localization of LC3B and P62 protein were detected by immunohistochemistry.PCR was used to detect the expression of BECN1,LC3B and P62 mRNA in the anterior capsule.The relative expression of autophagy-related proteins in the anterior capsule was detected by Western blot.The use of animals complied with Regulations on the Management of Experimental Ainimals from Shandong Eye Institute.Results Compared with the control group,transmission electron microscopy revealed that the autophagosomes of lens epithelial cells in model group was large and contained more mitochondria.Immunohistochemical method showed that the expression of LC3B and P62 proteins in the anterior capsule tissue of experiment group was stronger than that of the control group.The relative expression level of BECN1,LC3B and P62 mRNA in the experiment group was 1.48±0.10,2.62±0.15 and 1.89±0.20,respectively,which was higher than 1.10±0.02,1.10±0.05 and 1.01±0.01 in the control group,with significant differences between the two groups (t =6.64,14.25,6.14;all at P ＜ 0.05).The relative expression of BECN1,LC3B and P62 protein in the experiment group was 1.50±0.10,1.24±0.09 and 3.19± 1.04,respectively,which was higher than 1.00±0.00,1.00±0.00 and 1.00±0.00 in the control group,with significant differences between the two groups (t =8.75,6.10,3.65;all at P＜0.05).Conclusions The phenomenon of autophagy in lens epithelial cells of diabetic mice is abnormal,and autophagy dysfunction may play an important role in the formation of diabetic cataract.

Objective To evaluate the efficacy of one stage laparoscopic choledocholithotomy and cholecystectomy vs.ERCP cholecystolithiasis and cholecystectomy (staged) for cholecystolithiasis complicated with choledocholithiasis.Methods From Jan 2015 to Jun 2017,100 consecutive patients underwent randomized one-stage (TCLCBDE + LC) or two-stage (ERCP + subsequent LC) treatment for common bile duct (CBD) stones.Data evaluated were hospital costs,success rate of one-stage versus two-stage management,postoperative morbidity and GIQLI.Results 47 patients underwent ERCP plus LC two-stage treatment while 46 patients underwent one-stage treatment.Overall success rate of primary intervention for CBD stone clearance was 95.7％ and 97.8％ (P =1.0).Postoperative morbidity was 10.6％ vs.6.5％ (P =0.735),and postoperative hospital stay was (16 ± 5) days vs.(11.9 ± 2.9) days (P ＜ 0.01).One-stage laparoscopic transcystic management was the least costly option compared to two-stage management (19 415 ±2 167)yuan vs.(26 767 ±4 387)yuan (P ＜0.01).GIQLI improved faster in one-stage management group.Conclusion Transcystic one-stage management for gall stones with choledocholithiasis results in shorter hospital stay,lower costs and faster recovery than the two-stage management.