Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective: To evaluate the efficacy of the left spermatic vein transposition to the great saphenous vein in treating left varicocele (VC) secondary to nutcracker syndrome (NCS). Methods: Clinical data of 8 patients treated during Feb.2020 and Feb.2023 in our hospital were retrospectively analyzed.A meticulous preoperative evaluation of the vascular status of the spermatic vein and the great saphenous vein was performed using color Doppler ultrasound.A spermatic vein-great saphenous vein shunt surgery was performed in patients who were strictly selected.The clinical symptoms and hemodynamics of renal vein were compared before and after operation. Results: The median age of patients was 23.5(18-33) years.There was a notable reduction in post-exercise scrotal and lower back pain in all patients，and the score of scrotal pain decreased to 0 in 7 patients. The median quantification of urinary protein was 352.8(54.4-687.3) mg prior to surgical intervention，which significantly diminished to 125.5(25.9-255.1) mg 6 months after operation.Notably，3 cases of preoperative positive urine occult blood tests were undetectable in the subsequent postoperative assessments.The median peak blood flow velocity at the site of stenosis in the left renal vein measured at 74.4(48.7-117.6) cm/s preoperatively，subsequently reduced to 45.1(25.5-61.2) cm/s postoperatively.During the 6-month follow-up，no recurrence of varicocele，vascular anastomotic stenosis or thrombosis were observed. Conclusion: Our research indicates that spermatic vein to great saphenous vein bypass is safe and feasible in the treatment of left varicocele secondary to nutcracker syndrome for strictly selected patients，which can effectively alleviate renal vein congestion without significant complications.

Objective To elucidate the mechanism by which Huatan Anshen decoction inhibits neuronal apoptosis through modulation of the NOD-like receptor pyrin domain-containing protein 3(NLRP3)/interleukin-18(IL-18)/nuclear factor-activated B cell κ-light chain(NF-κB)signaling pathway.Methods The HT22 cell line derived from mouse hippocampal neurons were cultured in vitro,and serum containing Huatan Anshen Decoction was prepared from C57 mice after intragas tric administration.The optimal concentration of Huatan Anshen Decoction serum for intervention was determined with the CCK-8 method.Following treatment with different concentrations of drug-containing serum,lipopolysaccharide(LPS)was used to induce apoptosis in HT22 cells.Cell damage and apoptosis were assessed with the CCK-8 assay and Annexin V/PI staining.Western blotting and reverse transcription polymerase chain reaction was employed to measure the expression levels of NF-κB,apoptosis-associated speck-like protein containing(ASC),NLRP3,and Caspase-1,while enzyme-linked immunosorbent assay(ELISA)was used to detect IL-18 expression.The experiments was repeated after overexpression of NRLP3 to conduct single gene function verification.Results Serum containing Huatan Anshen Decoction significantly improved LPS-induced cellular damage and apoptosis in HT22 cells while reduced cellular L-lactate dehydrogenase,(L-LDH)levels(P＜0.05).Transcriptional expression of proteins related to the NLRP3/IL-18/NF-κB signaling pathway showed significant downregulation(P＜0.05).Additionally,it markedly decreased intracellular IL-18 levels.Furthermore,overexpression of NF-κB reversed the inhibitory effect of Huatan Anshen decoction-containing serum on HT22 cell apoptosis(P＜0.05).Conclusion Huatan Anshen Decoction can improve neuronal apoptosis via suppressing the NLRP3/IL-18/NF-κB signaling pathway.

Objective To elucidate the mechanism by which Huatan Anshen decoction inhibits neuronal apoptosis through modulation of the NOD-like receptor pyrin domain-containing protein 3(NLRP3)/interleukin-18(IL-18)/nuclear factor-activated B cell κ-light chain(NF-κB)signaling pathway.Methods The HT22 cell line derived from mouse hippocampal neurons were cultured in vitro,and serum containing Huatan Anshen Decoction was prepared from C57 mice after intragas tric administration.The optimal concentration of Huatan Anshen Decoction serum for intervention was determined with the CCK-8 method.Following treatment with different concentrations of drug-containing serum,lipopolysaccharide(LPS)was used to induce apoptosis in HT22 cells.Cell damage and apoptosis were assessed with the CCK-8 assay and Annexin V/PI staining.Western blotting and reverse transcription polymerase chain reaction was employed to measure the expression levels of NF-κB,apoptosis-associated speck-like protein containing(ASC),NLRP3,and Caspase-1,while enzyme-linked immunosorbent assay(ELISA)was used to detect IL-18 expression.The experiments was repeated after overexpression of NRLP3 to conduct single gene function verification.Results Serum containing Huatan Anshen Decoction significantly improved LPS-induced cellular damage and apoptosis in HT22 cells while reduced cellular L-lactate dehydrogenase,(L-LDH)levels(P＜0.05).Transcriptional expression of proteins related to the NLRP3/IL-18/NF-κB signaling pathway showed significant downregulation(P＜0.05).Additionally,it markedly decreased intracellular IL-18 levels.Furthermore,overexpression of NF-κB reversed the inhibitory effect of Huatan Anshen decoction-containing serum on HT22 cell apoptosis(P＜0.05).Conclusion Huatan Anshen Decoction can improve neuronal apoptosis via suppressing the NLRP3/IL-18/NF-κB signaling pathway.

Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.

Objective: To investigate the effects of plateau environment exposure on the reproductive system of male rats, so as to provide the reference for mechanisms of reproductive damage in plateau environment. Methods: Sixty SPF-grade 12-week-old male Wistar rats were randomly divided into the plain-exposed group, the 1 day-, 3 day-, 7 day-, 14 day- and 28 day- plateau-exposed groups. The rats in the plain-exposed group were raised under normal conditions for 28 days, while the rats in the plateau-exposed groups were raised in a simulated high-altitude plateau chamber. After the completion of the designated feeding periods, the rats were sacrificed under anesthesia, and testicular tissue and abdominal aortic blood were collected to detect the testicular index and evaluate sperm quality. Histological and cellular morphologies of the testicular tissue were analyzed. Additionally, the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) in the testicular tissue were determined, along with serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Conclusions Plateau environment may cause a decrease in testicular index and sperm quality, impair mitochondrial function, induce oxidative stress, and thus affect reproductive system of male rats. However, there are signs of self-repair in the reproductive system with the increase of exposure duration.

Objective:To evaluate the clinical outcomes of arthroscopic debridement combined with in situ ulnar nerve release in patients with osteoarthritic elbow stiffness complicated by tardy ulnar neuritis.Methods:A retrospective chart review was conducted on 36 patients with osteoarthritic elbow stiffness and tardy ulnar neuritis who underwent arthroscopic debridement and in situ ulnar nerve release between January 2018 and October 2022. The mean patient age was 51.3±6.5 years (range: 40-62 years), with 29 males and 7 females. The procedure was performed on 28 right and 8 left elbows, all on the dominant side. Radiographic classification of elbow osteoarthritis (OA) revealed 16 cases of Kellgren-Lawrence grade II, 15 cases of grade III, and 5 cases of grade IV. The duration of OA was 4.2±1.8 years (range: 2-8 years), and the duration of ulnar nerve compression symptoms was 4.6±3.2 months (range: 2 months-1 year). Elbow function and pain were assessed preoperatively and 12 months postoperatively using flexion-extension range of motion, the Mayo Elbow Performance Index (MEPI), and the Visual Analogue Scale (VAS) for pain. Ulnar nerve function was evaluated through grip strength, pinch strength, two-point discrimination of the little finger, and motor and sensory nerve conduction velocities (MNCV and SNCV).Results:The mean operation time was 151.4±16.2 minutes (range: 125-180 minutes), with an average hospital stay of 6.5±1.0 days (range: 5-8 days). One patient (2.8%) experienced skin necrosis at the ulnar nerve release incision, while all other incisions healed at the first stage. At the 12-month follow-up, significant improvements were observed in elbow extension [26.00° (20.00°, 30.00°) vs. 6.00° (5.00°, 10.00°), Z=-5.235, P<0.001], flexion range of motion [98.00° (88.25°, 100.00°) vs. 120.50° (109.00°, 128.00°), Z=-5.234, P<0.001], VAS pain scores (7.5±0.9 vs. 1.8±0.8, t=32.788, P<0.001), and MEPI [32.50 (26.25, 43.75) vs. 85.00 (80.00, 85.00), Z=-5.269, P<0.001]. Improvements in grip strength (24.1±2.4 N vs. 35.0±2.7 N, t=30.745, P<0.001), pinch strength (16.2±1.3 N vs. 23.8±1.7 N, t=40.239, P<0.001), two-point discrimination [16.00 (14.00, 18.00) mm vs. 5.00 (3.00, 7.00) mm, Z=-5.270, P<0.001], and MNCV (27.5±3.0 m/s vs. 41.6±3.0 m/s, t=53.673, P<0.001) / SNCV (25.1±2.7 m/s vs. 35.0±2.9 m/s, t=47.538, P<0.001) were also noted. At the 12-month follow-up, 5 patients (13.9%) had an elbow extension lag greater than 15° (range: 18°-20°), though elbow flexion recovered to at least 100°, sufficient for daily activities. One patient (2.8%) had incomplete relief of ulnar nerve symptoms postoperatively, but was generally satisfied with the outcome. Three patients (8.3%) experienced temporary worsening of ulnar nerve symptoms during rehabilitation, which improved with adjusted exercise routines, and the symptoms resolved by the 1-year follow-up. Conclusion:Arthroscopic debridement combined with in situ ulnar nerve release is a safe and effective treatment for osteoarthritic elbow stiffness complicated by tardy ulnar neuritis. This minimally invasive procedure is associated with a low complication rate and yields significant functional improvements.

Objective:To investigate the clinical efficacy of unicompartmental knee arthroplasty (UKA) in the treatment of medial compartment knee osteoarthritis (OA) with concomitant lateral discoid meniscus.Methods:A retrospective analysis was conducted on 13 patients (16 knees) who underwent UKA for medial compartment OA of the knee associated with lateral discoid meniscus at Central Hospital of Cangzhou between January 2016 and July 2021. The mean age of the patients was 59.1±7.7 years (range, 49-74 years), with a mean body mass index (BMI) of 28.9±1.7 kg/m 2 (range, 25.2-31.3 kg/m 2). Of the 13 patients, 7 were male (9 knees) and 6 were female (7 knees). The procedure was performed on 10 knees of the left leg and 6 knees of the right leg. Preoperative radiographic assessment showed that all patients had Kellgren-Lawrence grade 3-4 knee OA (9 knees with grade 3, 7 knees with grade 4). The average duration of knee pain was 6.0±1.5 years (range, 3-8 years). No surgical intervention was performed on the lateral discoid meniscus during the UKA procedure. The alignment of the lower limbs was assessed by measuring the hip-knee-ankle (HKA) angle using full-length weight-bearing X-rays. Functional outcomes were evaluated using the Hospital for Special Surgery (HSS) score, Oxford knee score (OKS), and American Knee Society (AKS) knee and function scores. The presence of lateral knee pain or tenderness along the lateral joint line was used to assess symptoms related to lateral meniscus injury. Results:The average surgical time for the 16 knees was 55.9±4.5 min (range, 48-62 min), and the mean length of hospital stay was 10.2±3.2 days (range, 7-15 days). The mean follow-up duration was 53.2±11.1 months (range, 36-68 months). At 6 months, 1 year, and the final follow-up, significant improvements were observed in HSS scores [57.00(54.25, 58.00) vs. 91.00 (89.25, 92.00) vs. 95.50(92.00, 97.00) vs. 96.50 (95.00, 97.75)], OKS [37.00(36.00, 39.00) vs. 15.00(15.00, 16.00) vs. 14.00(13.00, 14.00) vs. 13.00(12.25, 13.00)], AKS knee scores [52.00(50.00, 53.75) vs. 91.50(91.00, 92.00) vs. 95.00(95.00, 97.00) vs. 96.50 (95.00, 97.00)], and AKS function scores [53.00(45.00, 55.00) vs. 90.00(90.00, 90.00) vs. 95.00(92.00, 99.25) vs. 95.00(95.00, 100.00)] compared to preoperative values ( P<0.001). Statistically significant differences were found between the 6-month follow-up and the 1-year or final follow-up ( P<0.05), but no significant differences were observed between the 1-year and final follow-up ( P>0.05). Preoperative HKA angle was 8.00°(6.25°, 9.75°) of varus, whereas the postoperative HKA angle was 3.00° (3.00°, 3.75°) of varus. The postoperative alignment showed a significant reduction in varus deformity, with a statistically significant difference compared to preoperative values ( Z=-3.419, P=0.001). One knee developed symptomatic intra-articular loose body at 5 years postoperatively, which was successfully treated with arthroscopic removal. At the final follow-up, all prostheses were well-positioned, with no signs of loosening, subsidence, periprosthetic infection, or the need for revision surgery. No symptoms were indicative of lateral discoid meniscus injury were observed. Conclusion:UKA for the treatment of medial compartment knee OA in patients with lateral discoid meniscus yields favorable clinical outcomes, with significant improvements in knee function and pain relief, as well as stable midterm prosthesis performance.

Objective:To evaluate the role of transient receptor potential melastatin2 (TRPM2) in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.Methods:Sixty SPF-grade healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group M) and sevoflurane anesthesia+ TRPM2 inhibitor group (group M+ A). M and M+ A groups inhaled 2% sevoflurane for 5 h. In group M+ A, TRPM2 inhibitor ACA 20 mg/kg was intraperitoneally injected at 1 h before sevoflurane inhalation, and the equal volume of dimethyl sulfoxide was intraperitoneally injected in group C and group M. Morris water maze test was performed at 1 day after sevoflurane anesthesia. The escape latency, times of crossing the original platform and time spent in the original platform quadrant were collected. The expression of TRPM2 and necroptosis-related proteins (mixed lineage kinase domain-like protein [MLKL], receptor-interacting protein kinase-1 [RIPK1], phosphorylated MLKL [p-MLKL], and phosphorylated RIPK1 [p-RIPK1]) was detected by Western blot. The cytosolic Ca 2+ concentration in and necroptosis rate of hippocampal neurons were determined by flow cytometry. Results:Compared with group C, the escape latency was significantly prolonged, the times of crossing the original platform were decreased and the time spent in the original platform quadrant was shortened, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was up-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were increased in group M and group M+ A ( P<0.05). Compared with group M, the escape latency was significantly shortened, the times of crossing the original platform were increased, and the time spent in the original platform quadrant was prolonged, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was down-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were decreased in group M+ A ( P<0.05). Conclusions:Hippocampal TRPM2 is involved in the process of sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.