Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Objective We report a case of application of third-generation sequencing(TGS)combined with preimplantation genetic testing(PGT)for successful prevention of hereditary spastic paraplegia(HSP)caused by SPAST gene mutations and assess the value of PGT-M and TGS in managing hereditary spastic paraplegia.Methods A family affected by HSP underwent whole exon sequencing(WES),and a c.1699G>T mutation in the SPAST gene was identified.The mutation site in the proband was confirmed through Sanger sequencing.A single nucleotide polymorphism(SNP)site flanking the SPAST gene mutation was selected as the genetic linkage marker,and a SNP haplotype carrying the mutated gene was constructed.Ovarian stimulation using an antagonist regimen was performed for oocyte retrieval,followed by intracytoplasmic sperm injection(ICSI)and embryo culture.Blastocyst trophectoderm cells were biopsied for preimplantation genetic testing for monogenic disorders(PGT-M)to allow the selection of disease-free embryos for transfer.Results In this cycle,a total of 20 oocytes were retrieved,among which 18 were successfully fertilized to result in 12 blastocysts eligible for biopsy.Genetic testing revealed that all the 12 blastocysts were successfully amplified and confirmed as euploidy.Among them,8 blastocysts did not carry paternal mutations,and a high-quality euploid embryo was selected for frozen embryo transfer(FET).Subsequent amniotic fluid testing during pregnancy confirmed the absence of paternal mutations in the fetus,resulting in the birth of a healthy baby girl.Conclusion For cases of genetic diseases with missing pedigree data,the application of third-generation sequencing and PGT-M technique can effectively block vertical transmission of SPAST gene mutation to the offspring,avoid pregnancy with an aneuploid embryo,and help families with autosomal dominant HSP obtain healthy offsprings.

Objective We report a case of application of third-generation sequencing(TGS)combined with preimplantation genetic testing(PGT)for successful prevention of hereditary spastic paraplegia(HSP)caused by SPAST gene mutations and assess the value of PGT-M and TGS in managing hereditary spastic paraplegia.Methods A family affected by HSP underwent whole exon sequencing(WES),and a c.1699G>T mutation in the SPAST gene was identified.The mutation site in the proband was confirmed through Sanger sequencing.A single nucleotide polymorphism(SNP)site flanking the SPAST gene mutation was selected as the genetic linkage marker,and a SNP haplotype carrying the mutated gene was constructed.Ovarian stimulation using an antagonist regimen was performed for oocyte retrieval,followed by intracytoplasmic sperm injection(ICSI)and embryo culture.Blastocyst trophectoderm cells were biopsied for preimplantation genetic testing for monogenic disorders(PGT-M)to allow the selection of disease-free embryos for transfer.Results In this cycle,a total of 20 oocytes were retrieved,among which 18 were successfully fertilized to result in 12 blastocysts eligible for biopsy.Genetic testing revealed that all the 12 blastocysts were successfully amplified and confirmed as euploidy.Among them,8 blastocysts did not carry paternal mutations,and a high-quality euploid embryo was selected for frozen embryo transfer(FET).Subsequent amniotic fluid testing during pregnancy confirmed the absence of paternal mutations in the fetus,resulting in the birth of a healthy baby girl.Conclusion For cases of genetic diseases with missing pedigree data,the application of third-generation sequencing and PGT-M technique can effectively block vertical transmission of SPAST gene mutation to the offspring,avoid pregnancy with an aneuploid embryo,and help families with autosomal dominant HSP obtain healthy offsprings.

Objective:To investigate the short-term outcomes of robot-assisted pancreato-duodenectomy (RPD) performed by one single surgeon.Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 240 patients who were performed RPD by one single surgeon at The First Affiliated Hospital of Sun Yat-sen University from July 2016 to October 2023 were collected. There were 130 males and 110 females, aged 59(19)years. All RPD were performed by the same surgeon. Observation indicators: (1) surgical situations; (2) postoperative pathological examination and outcome of patients. Measurement data with normal distribution were expressed as Mean± SD, and measurement data with skewed distribution were expressed as M(IQR). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical situations. Of 240 patients, 15 cases underwent combined vascular resection and reconstruction, and 13 patients were combined with other operations simultaneously. Of 240 patients, 4 cases converted to open surgery, with the conversion rate as 1.67%. The operation time of 240 patients was 458(152)minutes, volume of intraopera-tive blood loss was 50(50)mL, intraoperative erythrocyte transfusion was required in 17 patients. The R 0 resection rate was 99.17%(238/240), the number of lymph nodes harvested was 10(6) and duration of postoperative hospital stay was 17(12)days. (2) Postoperative pathological examination and outcome of patients. Of 240 patients, 51 cases were pancreatic ductal adenocarcinoma, 41 cases were ampullary carcinoma, 41 cases were neuroendocrine neoplasms, 35 cases were pancreatic cystic neoplasms, 28 cases were duodenal carcinoma and 44 cases were other pathologic types. Of 99 patients with major complications, there were 57 cases with clinically relevant postoperative pancreatic fistula, 44 cases with postoperative delayed gastric empty, 11 cases with postoperative biliary fistula, 8 cases with postoperative chyle fistula, 14 cases with incision infec-tion, and 24 cases with postoperative hemorrhage. Multiple complications might occur to the same patient. Reoperation was performed in 6 of the 240 patients. One patient died within 30 days after surgery. Twenty-four patients returned to hospital within 30 days after discharge. Conclusions:RPD performed by one single surgeon is safe and feasible, with favorable short-term outcomes, which can be performed in medical centers with experiences in robot-assisted pancreatic surgery.

Objective:To evaluate the safety and short-term efficacy of robotic-assisted resection for Bismuth-Corlette type Ⅲ and Ⅳ perihilar cholangiocarcinoma in Department of Pancreatobiliary Surgery,The First Affiliated Hospital,Sun Yat-sen University Methods:The clinical data of Bismuth-Corlette type Ⅲ and Ⅳ perihilar cholangiocarcinoma patients who have undergone robotic-assisted resection at The First Affiliated Hospital,Sun Yat-sen University between July 2017 and May 2023 were retrospectively studied.The clinicopathological features and perioperative outcomes of the patients were analyzed. Results:A total of 9 patients with Bismuth-Corlette type Ⅲ or Ⅳ perihilar cholangiocarcinoma,including 4 type Ⅲa patients,4 type Ⅲ b patients and 1 type Ⅳ patient,received robotic-assisted resection.1 patient converted to open surgery.The median operation time was 645 min[interquartile range(IQR):554-745 min],the median intraoperative blood loss was 300 mL(IQR:150-650 mL),and the median number of lymph node retrieval was 11(IQR:6-12).7 patients(77.8％)had R0 resection.5 patients(55.6％)had postoperative major complications(Clavein-Dindo classification was Ⅲ-Ⅴ),including intra-abdominal infection in 2 patients,liver function failure in 2 patients and upper gastrointestinal bleeding in 1 patient.1 patient underwent reoperation for the jejuno-jejunostomy bleeding 19 d after the initial operation and achieved good recovery.1 patient died within 30 d after initial operation due to liver function failure.The median length of postoperative hospital stay was 18 d(IQR:10-32 d). Conclusion:Robotic-assisted resection for Bismuth-Corlette type Ⅲ and Ⅳ perihilar cholangio-carcinoma is technically feasible and safe with good short-term efficacy,and can be performed in large-volume centers with ample experience in robotic-assisted hepatopancreatobiliary surgery.

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,