Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To compare the clinical effects of total hip arthroplasty(THA)with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH).Methods The data on 46 patients who underwent THA for unilateral Crowe ⅣDDH between 2012 and 2017 were analyzed retrospectively.They were divided into two groups according to the different surgical methods.There were 24 patients in the osteotomy group,3 males and 21 females,with an average age of(47.3±9.0)years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group,2 males and 20 females,with an average age of(51.6±8.3)years old ranged from 40 to 61 years old.The operative time,bleed loss,postoperative drainage volume,postoperative com-plications,ROM of hip,Harris hip score,limb length discrepancy(LLD),and radiological data were recorded.The femoral dislo-cation height and the implantation depth of sleeve were measured.Results All patients were followed up.The mean follow-up time was(3.8±1.2)years ranged from 2 to 6 years in the osteotomy group and(3.2±0.9)years ranged from 1 to 5 years in the non-os-teotomy group.The operative time(136.8±18.9)min,bleed loss(709.8±89.4)ml,postoperative drainage volume(308.8±98.2)ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min,(516.5±103.3)ml,(245.3±79.3)ml(P＜0.05).The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups(P＜0.05),but there was no significant difference between two groups(P＞0.05).The LLD at last follow up was sig-nificantly increased compared with preoperative LLD in two groups,the LLD in non-osteotomy group(0.7±0.2)cm showed signif-cant smaller than the two osteotomy group(1.2±0.4)cm.Between osteotomy and non-osteotomy groups,the preoperative range of motion of hip joint[(89.5±19.7)°vs(102.5±16.8)°],the preoperative height of dislocation of femoral head[(4.56±0.61)cm vs(3.10±0.73)cm],the proximal implant depth of S-ROM[(0.93±0.36)cm vs(1.67±0.28)cm]was significantly different(P＜0.05).Eleven patients in the osteotomy group still had claudication,and 4 patients in the non-osteotomy group had mild claudica-tion(P＜0.05).In non-osteotomy group,3 patients developed nerve injury(1 patient of sciatic nerve,2 patients of femoral nerve)and 1 case developed periprosthetic fracture.In osteotomy group,2 case of dislocation and 2 cases of periprosthetic fractures.Conclusion Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD.However,osteotomy is more complex and time-consuming,limb length difference is greater,and the incidence of claudica-tion is higher.Furthermore,patients with smaller preoperative hip mobility,higher femoral dislocation,limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

Objective To evaluate the clinical application effect of fracture liaison service(FLS)mode after percutaneous vertebroplasty(PVP)/percutaneous kyphoplasty(PKP)for thoracolumbar fragility fracture.Methods A prospective study was conducted,and 762 patients with thoracolumbar fragility fracture who underwent PVP/PKP in the department of orthopedics in our hospital from January 2018 to May 2021 were included and divided into the control group(374 cases)and the observation group(388 cases)according to the random number table method.Patients in the control group received routine osteoporosis intervention,while the patients in the observation group implemented FLS through Blue Bull Medical Care or Chronic Health APP on the basis of the control group to systematically manage the osteoporosis treatment after discharge.The follow-up lasted for 12 months,and the 8-item Morisky medication adherence scale(MMAS-8)score,pain visual analogue scale(VAS)score,Oswestry disability index(ODI)score and Hamilton depression rating scale(HAMD)score at discharge,and 6 months and 12 months after discharge of the two groups were compared.The incidences of re-fracture and constipation 6 months and 12 months after discharge of the two groups were compared.The Cobb angle and bone mineral density T-value of injured vertebrae 6 months and 12 months after discharge of the two groups were compared.Results There was no statistically significant difference in the MMAS-8 score,VAS score,ODI score or HAMD score at discharge of patients between the two groups(P>0.05).The VAS score,ODI score and HAMD score 6 months and 12 months after discharge in the observation group were lower than those in the control group(P<0.05),the MMAS-8 score in the observation group was higher than that in the control group(P<0.05),and the incidences of re-fracture and constipation in the observation group were lower than those in the control group(P<0.05).There was no statistically significant difference in the Cobb angle of injured vertebrae 12 months after discharge of patients between the two groups(P>0.05).The bone mineral density T-value 12 months after discharge in the observation group was higher than that in the control group(P<0.05).Conclusion The FLS mode can significantly improve the medication compliance of patients,relieve pain,depression and constipation,improve bone mineral density,and significantly reduce the incidence of vertebral re-fracture in patients after vertebral augmentation surgery;however,it has no significant effect on the Cobb angle of injured vertebrae.

Objective To investigate the curative effect of suture anchor(SA)repair combined with open reduction and internal fixation(ORIF)on patients with ankle joint fracture(AF)combined with deltoid ligament injury(DLI).Methods A total of 138 patients with AF combined with DLI admitted to our hospital from January 2020 to September 2022 were selected and divided into the control group(69 cases)and the observation group(69 cases)according to the random number table method.Patients in the control group were treated with ORIF,while patients in the observation group were treated with SA repair on the basis of the control group.The clinical efficacy,American Orthopedic Foot and Ankle Society(AOFAS)score,visual analogue scale(VAS)score,talus inclination angle,medial malleolar space of affected side,bone metabolic indexes[serum bone gla protein(BGP),β-collagen degradation product(β-CTX)]levels and the incidence of complications before and 3 months after treatment were compared between the two groups.Results The total effective rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Compared with before treatment,the talus inclination angle,medial malleolar space of affected side,VAS score,β-CTX level 3 months after treatment of patients in the two groups were reduced,while the AOFAS score and BGP level were increased,and the differences were statistically significant(P<0.05).After treatment,the AOFAS score and BGP level in the observation group were higher than those in the control group,while the talus inclination angle and medial malleolar space of affected side were smaller than those in the control group,and the VAS score and β-CTX level were lower than those in the control group,with statistically significant differences(P<0.05).The total incidence of complications in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion SA repair has a definite therapeutic effect on AF combined with DLI,which can improve patients' symptoms and promote the recovery of ankle joint function and bone metabolism.

Intramedullary needle(IMN)has the advantages of high healing rate and low incidence of complications in treatment of tibial fracture,and has become one of the most commonly used fixation methods for the treatment of tibial fracture.However,due to the patient's own factors,fracture location and fracture type,infection and surgical treatment,bone nonunion after IMN still occurs in clinic.Bone nonunion leads to the increase of medical cost and prolonged the hospitalization time of patients,which causes great pain to patients,and also brings great challenges to the treatment of orthopedic surgeons.Therefore,this paper reviews the influencing factors of bone nonunion after IMN for tibial fracture,in order to provide reference for clinical treatment.

The prevalence of Lyme disease in endogenous populations in Urumqi,Xinjiang was investigated.In total,795 serum samples were collected from residents of three townships in the surrounding area of Urumqi City from 2022 to 2023,which included 383 from Lucaogou Town,145 from Shuixigou Town,and,267 from Tori Township.Serum levels of IgG and IgM antibodies were screened with an enzyme linked immunosorbent assay(ELISA)and confirmed by western blot(WB)analysis.Clinical data of WB-positive indi-viduals were collected and comprehensive analysis was con-ducted for case diagnosis.The chi square test was used for statistical analysis of the results and the P＜0.05 was consid-ered statistically significant.In total,110(13.84％)of 795 samples were positive.The positivity rates was higher in females than males[16.26％(73/449)vs.10.69％(37/346),x2=5.076,P=0.024],while there was no significant difference among age groups(x2=2.569,P=0.766).The positivity rates for serum antibodies in Shuixigou Town,Lucaogou Town,and Tuoli Township were 17.98％(48/267),14.48％(21/145),and 10.70％(41/383),respectively,with a significantly higher rate in Tuoli Township than Lucaogou Town(x2=7.041,P=0.008).Of 110 individuals who were initially positive for IgG and IgM antibodies with the ELISA,82(10.31％)were con-firmed positive by WB analysis.In total,20(2.52％)patients were diagnosed with Lyme disease based on clinical manifesta-tions.Lyme disease is epidemic among the population in Urumqi,as the infection rate is higher than the national average.Hence,continued surveillance is recommended for prevention of Lyme disease.