ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Objective To observe the clinical effect of ultrasound-guided nerve block combined with arc edge needle-scalpel in the treatment of cervical spondylotic radiculopathy.Methods 160 cases were randomly divided into 4 groups from A to D,40 cases in each group.Group A was given nerve block,group B was given ultrasound-guided nerve block,group C was given arc edge needle-scalpel,and group D was given ultrasound-guided nerve block combined with arc edge needle-scalpel for 4 weeks.The McGill pain scale,cervical dysfunction index,cervical motion(angle of cervical left and right rotation,anterior flexion,posterior extension and lateral flexion),myoelectric-evoked potentiall(median nerve and ulnar nerve conduction velocity,latency),arterial blood flow velocity(average vertebral artery and basal artery flow velocity,end-diastolic blood flow velocity)were observed.The serum levels of neuron-specific enolase(NSE),β-endorphin(β-EP),lipoprotein-associated phospholipase A2(LpPLA2),6-ketoprostaglandin E1α(6-keto-PGE1α)were measured.The clinical efficacy and safety of each group were observed.Results The response rate in group D was taller than that in group A and group B significantly(χ2=6.605,P=0.013;χ2=4.073,P=0.044).Compared with the other three groups,the McGill pain,NDI,NSE,LpPLA2 and 6-keto-PGE1α in group D decreased significantly(P<0.05),the β-EP increased significantly(P<0.05),and the angles of left and right cervical rotation,anterior flexion,posterior extension and lateral flexion increased significantly(P<0.05),and median nerve and ulnar nerve conduction velocity,vertebral artery and basilar artery average blood flow velocity,end diastolic blood flow velocity increased significantly(P<0.05),and median nerve and ulnar nerve latency decreased significantly(P<0.05).The safety index of group D was higher than that in group A significantly(χ2=5.641,P=0.018).Conclusion Ultrasound-guided nerve block combined with arc edge needle-scalpel can relieve neck and shoulder pain,improve cervical spine function and reduce complications in patients with cervical spondylotic radiculopathy.

Objective To observe the clinical effect of ultrasound-guided nerve block combined with arc edge needle-scalpel in the treatment of cervical spondylotic radiculopathy.Methods 160 cases were randomly divided into 4 groups from A to D,40 cases in each group.Group A was given nerve block,group B was given ultrasound-guided nerve block,group C was given arc edge needle-scalpel,and group D was given ultrasound-guided nerve block combined with arc edge needle-scalpel for 4 weeks.The McGill pain scale,cervical dysfunction index,cervical motion(angle of cervical left and right rotation,anterior flexion,posterior extension and lateral flexion),myoelectric-evoked potentiall(median nerve and ulnar nerve conduction velocity,latency),arterial blood flow velocity(average vertebral artery and basal artery flow velocity,end-diastolic blood flow velocity)were observed.The serum levels of neuron-specific enolase(NSE),β-endorphin(β-EP),lipoprotein-associated phospholipase A2(LpPLA2),6-ketoprostaglandin E1α(6-keto-PGE1α)were measured.The clinical efficacy and safety of each group were observed.Results The response rate in group D was taller than that in group A and group B significantly(χ2=6.605,P=0.013;χ2=4.073,P=0.044).Compared with the other three groups,the McGill pain,NDI,NSE,LpPLA2 and 6-keto-PGE1α in group D decreased significantly(P<0.05),the β-EP increased significantly(P<0.05),and the angles of left and right cervical rotation,anterior flexion,posterior extension and lateral flexion increased significantly(P<0.05),and median nerve and ulnar nerve conduction velocity,vertebral artery and basilar artery average blood flow velocity,end diastolic blood flow velocity increased significantly(P<0.05),and median nerve and ulnar nerve latency decreased significantly(P<0.05).The safety index of group D was higher than that in group A significantly(χ2=5.641,P=0.018).Conclusion Ultrasound-guided nerve block combined with arc edge needle-scalpel can relieve neck and shoulder pain,improve cervical spine function and reduce complications in patients with cervical spondylotic radiculopathy.

Objectives:There is a lack of long-term follow-up study results on severe microvascular complications in a larger Chinese population with diabetes.This study aims to explore long-term impact of newly diagnosed diabetes(NDD)on the incidence and risk of severe microvascular complications.Methods:A total of 598 NDD and 493 normal glucose tolerance(NGT)subjects were included in this study in 1986.By questionnaire and systematic case review,the occurrence of severe microvascular complications,including severe diabetic retinopathy,severe diabetic nephropathy,and severe diabetic neuropathy,was followed up and collected over a period of 34 years.Results:The cumulative incidence of severe microvascular complications in the NDD population was 65.03%(95%CI:58.90%-70.48%)over 34 years,significantly higher than that in the NGT population(16.8%,95%CI:12.64%-20.11%).After adjusting for related risk factors,the risk of severe microvascular complications in the NDD population was 7.08 times than that of the NGT population(HR=7.08,95%CI:5.09-9.84,P<0.0001).Stratified analysis by sex showed that the cumulative incidence and risk of severe microvascular complications were slightly higher in male NDD population(68.02%,95%CI:57.27%-76.61%;HR=9.45,95%CI:5.78-15.47,P<0.0001)than in female NDD population(63.37%,95%CI:55.69%-70.09%;HR=5.86,95%CI:3.75-9.16,P<0.0001);however,the cumulative incidence increased more rapidly in women during the follow-up period of 10-25 years.Conclusions:The incidence and risk of severe microvascular complications in diabetes were significantly higher than those in the NGT population;and the incidence of severe vascular complications increased rapidly after the duration of diabetes exceeded 10 years,indicating that strict control of blood glucose in the early stage of diabetes is of vital importance.

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

Objective:To analyze the differences in paraspinal muscles between patients with degenerative lumbar spinal stenosis (DLSS) with or without spondylolisthesis and to assess the correlation between these differences and lumbar facet joint degeneration.Methods:The data of 68 patients with DLSS who underwent surgical treatment in our hospital from January 2021 to April 2023 was retrospectively analyzed. Of these, 22 were male (32.4%) and 46 were female (67.6%), with an average age of 69.7±5.9 years (range: 56-80 years). The DLSS group included 35 patients without spondylolisthesis [13 males (37.1%) and 22 females (62.9%)], average age 68.5±5.9 years (range: 56-80 years), while the DLSS+degenerative spondylolisthesis (DS) group included 33 patients with spondylolisthesis [9 males (27.3%) and 24 females (72.7%)], average age 70.9±5.7 years (range: 58-80 years). Magnetic resonance imaging (MRI) scans of the L 3-S 1 intervertebral disc levels were collected from all patients. Using ImageJ software, the cross-sectional area (CSA) and percentage of fat infiltration area (FIA%) of the erector spinae and multifidus muscles were measured. Additionally, the facet joint angle (FJA), facet overhang (FO), and facet effusion (FE) were evaluated using Surgimap software, and their correlation with CSA and FIA% of the paraspinal muscles was analyzed. Results:The FJA and FO in the DLSS+DS group (50.16°±11.08° and 7.67±2.25 mm) were significantly larger than those in the DLSS group (43.51°± 7.75° and 3.88±1.98 mm) ( P<0.05). However, differences in FE between the two groups were not statistically significant. The cross-sectional areas of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (576.66±112.70 mm 2,, 782.72±141.49 mm 2, and 817.88±185.22 mm 2,, respectively) were significantly smaller than those in the DLSS group (647.37±165.44 mm 2,, 881.20±202.10 mm 2,, and 995.06±211.25 mm 2,, respectively) ( P<0.05). The FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (11.47%±5.14%, 14.84%±6.15%, 20.82%±7.41%) were significantly higher than those in the DLSS group (6.27%±2.83%, 10.81%±4.84%, 16.17%±5.88%) ( P<0.05). Similarly, the FIA% of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in the DLSS+DS group (18.04%±5.88%, 19.67%±5.78%, 19.31%±8.61%) were significantly higher than those in the DLSS group (9.85%±4.39%, 12.27%±3.70%, 14.65%±3.82%) ( P<0.05). No statistically significant differences were found in the CSA of the erector spinae at these levels between the two groups. The CSA of the multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in both groups were negatively correlated with FJA and FO ( r=-0.318, P=0.008; r=-0.381, P=0.001; r=-0.439, P<0.001; r=-0.290, P=0.016; r=-0.315, P=0.009; r=-0.479, P<0.001). The FIA% of the erector spinae at L 3, 4, L 4, 5, and the multifidus muscles at L 4, 5 and L 5S 1 were positively correlated with FJA ( r=0.352, P=0.003; r=0.344, P=0.004; r=0.300, P=0.013; r=0.359, P=0.003). Additionally, the FIA% of the erector spinae at L 3, 4, L 4, 5, and L 5S 1, and the multifidus muscles at L 3, 4 and L 4, 5 were positively correlated with FO ( r=0.409, P=0.001; r=0.248, P=0.042; r=0.277, P=0.022; r=0.500, P<0.001; r=0.447, P<0.001). There was no correlation between FE and CSA or FIA% of the erector spinae and multifidus muscles at L 3, 4, L 4, 5, and L 5S 1 in either group. Furthermore, FJA was positively correlated with FO ( r=0.369, P=0.002), but no correlation was observed between FE and FJA or FO. Conclusion:Compared to patients with lumbar spinal stenosis, those with degenerative lumbar spinal stenosis with spondylolisthesis exhibit more severe paraspinal muscle atrophy, a more sagittal orientation of the facet joints, and a higher degree of facet joint osteoarthritis. Patients with larger FJA and FO show more severe paraspinal muscle atrophy.

OBJECTIVE：To study the effect s of Bifidobacterium combined with L-carnitine on intestinal flora of dysbacteriosis diarrhea model rats. METHODS ：Totally 30 SD rats were randomly divided into blank control group ，model group ，probiotics group（Bifidobacterium triple viable enteric coated capsules 70 mg/mL），L-carnitine group （L-carnitine injection 50 mg/mL）and L-carnitine+probiotics group （L-carnitine injection 50 mg/mL+Bifidobacterium triple viable enteric coated capsules 70 mg/mL）. Except for blank control group ，the rats in other groups were given 50 mg/mL clindamycin phosphate intragastrically （2 mL/rat， once a day ，for 4 consecutive days ）to establish the model of dysbacteriosis diarrhea. On the 5th day of the experiment ，the rats in administration groups were given corresponding drugs intragastrically ，blank control group and model group were given equal volume of normal saline intragastrically ；with the dosage volume of 1 mL/rat，once a day ，for consecutive 7 days. The general situation of rats in each group was observed during the experiment. The feces of normal control group and model group at the end of the modeling and the feces of the rats in administration group after the last administration were collected for genomic DNA extraction，polymerase chain reaction amplification ，library construction and high-throughput sequencing. After processing ，the effective data were analyzed by operational taxonomic unitsclustering and species annotation ，as well as Alpha and Beta diversity of compared with blank control group ，grade 1 feces and grade 2feces were found in model group. The diversity and richness of intestinal flora ，the ratio of Firmicutes/Bacteroidetes and zhongjuanwang7@163.com the abundance of probiotics such as Lactobacillus， Bifidobacterium and Ackermann were significantly decreased （P＜0.05），while the abundance of pathogenic bacteria such as Enterococcus was significantly increased （P＜0.05）. At the end of the recovery period ，compared with model group ，the activity，fecal morphology and color of rats in probiotics group ，L-carnitine group and L-carnitine+probiotics group returned to normal，and the diversity and richness of intestinal flora had no significant difference （P＞0.05）. However ，the abundance of Lactobacillus in intestinal tract was increased to a certain extent ，and the abundance of Ackermann in intestinal tract of rats in L-carnitine+probiotics group was significantly increased （P＜0.05）. CONCLUSIONS ：Although Bifidobacterium combined with L-carnitine have no significant effect on improving the diversity and richness of intestinal flora in dysbacteriosis diarrhea model rats，it could increase the abundance of probiotics to a certain extent.