Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

Objective:To explore the differences in resting-state brain functional activity in obsessive-compulsive disorder (OCD) patients with and without sensory phenomena (SP).Methods:Clinical data from 102 OCD patients (60 males, 42 females; age 18-50(27±8) years) who visited the OCD outpatient clinic at the Affiliated Brain Hospital of Nanjing Medical University between August 2021 and December 2022 were prospectively collected. Based on the presence of sensory phenomena, patients were categorized into 70 cases with sensory phenomena (Sensory Phenomena Group) and 32 cases without sensory phenomena (Non-Sensory Phenomena Group). Additionally, 50 age-matched healthy controls (Control Group, 24 males, 26 females; age 18-49(25±6) years) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) was analyzed using the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) between differential brain regions. One-way ANOVA and post-hoc tests were used to compare group differences. Spearman correlation and binary logistic stepwise regression were applied to analyze the associations between SP and brain functional activity.Results:Compared to healthy controls, OCD patients showed decreased ALFF in bilateral middle frontal gyri, left superior frontal gyrus, right angular gyrus, and right supramarginal gyrus ( F=17.29-32.99, all P<0.05). The SP group exhibited increased ALFF in the right triangular part of the inferior frontal gyrus ( F=23.47, P<0.05) and decreased ALFF in the left superior parietal gyrus and left postcentral gyrus ( F=18.80, 15.04; both P<0.05). The non-SP group demonstrated increased ALFF in the left supramarginal gyrus and left postcentral gyrus ( F=19.64, 15.04; both P<0.05) and decreased ALFF in the left superior frontal gyrus, right middle frontal gyrus, and left angular gyrus ( F=17.29-35.52, all P<0.05). Reduced FC was observed between the left middle frontal gyrus and left angular gyrus, left middle frontal gyrus and right angular gyrus and left and right angular gyri ( F=17.29-23.47, all P<0.05). The SP group showed lower FC between the left middle frontal and left angular gyrus than the non-SP group ( F=23.47, P<0.05). Positive correlations with SP were found for ALFF in the right triangular part of the inferior frontal gyrus, left superior frontal gyrus, and right middle frontal gyrus (r=0.40, 0.35, 0.31; all P<0.05). Negative correlations were observed for ALFF in the left supramarginal gyrus, left superior parietal gyrus, and left postcentral gyrus (r=-0.38, -0.47, -0.52; all P<0.05) and FC between the left middle frontal gyrus-left angular gyrus and left middle frontal gyrus-right angular gyrus (r=-0.24, -0.21; both P<0.05). OCD patients with increased ALFF in the left superior frontal gyrus and right middle frontal gyrus, along with decreased ALFF in the left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and reduced FC between the left middle frontal gyrus-right angular gyrus, had a higher likelihood of SP (log OR (95% CI)=8.5(4.0-14.2), 8.0(1.7-16.4), -8.9(-15.2--4.4), -5.2 (-9.1--2.3), -4.1(-6.9--1.7), -7.0(-13.2--1.8); all P<0.05). Conclusion:Altered functional activity in the left superior frontal gyrus, right middle frontal gyrus, left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and abnormal FC between the left middle frontal gyrus and right angular gyrus represent key neuroimaging features of OCD patients with SP.

[Objective] To investigate the protective effect of Salvia miltiorrhiza injection (SMI) on the kidneys of HBOC-CHP01 resuscitated haemorrhagic shock rats. [Methods] A 50% haemorrhagic shock rat model was established, with 12 rats divided into two groups: SMI + HBOC-CHP01 group and HBOC-CHP01 group, with 6 rats in each group. The rats in the SMI+ HBOC-CHP01 group were given an equal volume of HBOC-CHP01 for resuscitation after haemorrhagic shock, and an 8 mL/kg dose of SMI. Rats in the HBOC-CHP01 group were resuscitated by administering an equilibrium blood loss volume of HBOC-CHP01 and given an 8 mL/kg dose of 0.9% NaCl solution. Blood was taken from rats at five points: before bloodletting (baseline), during haemorrhagic shock (HS), immediately after resuscitation (RS0h), 1 h after resuscitation (RS1h), and 24 h after resuscitation (RS24h). A blood gas analyser was used to detect the lactate level (Lac), glucose content (Glu), residual base (BEecf), pH, bicarbonate (HCO3-), high iron haemoglobin (MetHb). White blood cells (WBC), platelets (PLT), haemoglobin content (Hb), carboxyhaemoglobin (COHb) were detected using a quintuple classification. Blood creatinine (SCr), uric acid (UA), kidney-related indexes were detected using biochemistry instrument. Kidney tissues of the rats were taken after 24 h of resuscitation and after execution, and the inflammation of kidneys of the rats of the two groups was analyzed using HE staining. Fluorescence staining was used to detect the level of ROS in the kidneys of rats in both groups. [Results] At RS 0h, the Beecf, Glu and Lac levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group, and the pH level of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group, and the Glu levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group at RS 1h. At RS 0h, the WBC, PLT and COHb contents of rats in the SMI+HBOC-CHP01 group were all significantly higher than those of rats in the HBOC-CHP01 group, and at RS 1h, the WBC content of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group; at RS 1h, the UA content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the SCr content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the inflammation level of kidney tissues of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC -CHP01 group rats, and the ROS and MPO levels in the kidney tissues of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group. [Conclusion] The combination of Salvia miltiorrhiza injection during the resuscitation of rats with severe haemorrhagic shock by HBOC-CHP01 can alleviate renal injury by reducing inflammatory response and oxidative stress.

DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.
DNA End-Joining Repair/physiology* ; Gene Editing/methods* ; Mycobacterium/physiology* ; DNA Breaks, Double-Stranded ; Humans

Objective:To explore the differences in resting-state brain functional activity in obsessive-compulsive disorder (OCD) patients with and without sensory phenomena (SP).Methods:Clinical data from 102 OCD patients (60 males, 42 females; age 18-50(27±8) years) who visited the OCD outpatient clinic at the Affiliated Brain Hospital of Nanjing Medical University between August 2021 and December 2022 were prospectively collected. Based on the presence of sensory phenomena, patients were categorized into 70 cases with sensory phenomena (Sensory Phenomena Group) and 32 cases without sensory phenomena (Non-Sensory Phenomena Group). Additionally, 50 age-matched healthy controls (Control Group, 24 males, 26 females; age 18-49(25±6) years) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) was analyzed using the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) between differential brain regions. One-way ANOVA and post-hoc tests were used to compare group differences. Spearman correlation and binary logistic stepwise regression were applied to analyze the associations between SP and brain functional activity.Results:Compared to healthy controls, OCD patients showed decreased ALFF in bilateral middle frontal gyri, left superior frontal gyrus, right angular gyrus, and right supramarginal gyrus ( F=17.29-32.99, all P<0.05). The SP group exhibited increased ALFF in the right triangular part of the inferior frontal gyrus ( F=23.47, P<0.05) and decreased ALFF in the left superior parietal gyrus and left postcentral gyrus ( F=18.80, 15.04; both P<0.05). The non-SP group demonstrated increased ALFF in the left supramarginal gyrus and left postcentral gyrus ( F=19.64, 15.04; both P<0.05) and decreased ALFF in the left superior frontal gyrus, right middle frontal gyrus, and left angular gyrus ( F=17.29-35.52, all P<0.05). Reduced FC was observed between the left middle frontal gyrus and left angular gyrus, left middle frontal gyrus and right angular gyrus and left and right angular gyri ( F=17.29-23.47, all P<0.05). The SP group showed lower FC between the left middle frontal and left angular gyrus than the non-SP group ( F=23.47, P<0.05). Positive correlations with SP were found for ALFF in the right triangular part of the inferior frontal gyrus, left superior frontal gyrus, and right middle frontal gyrus (r=0.40, 0.35, 0.31; all P<0.05). Negative correlations were observed for ALFF in the left supramarginal gyrus, left superior parietal gyrus, and left postcentral gyrus (r=-0.38, -0.47, -0.52; all P<0.05) and FC between the left middle frontal gyrus-left angular gyrus and left middle frontal gyrus-right angular gyrus (r=-0.24, -0.21; both P<0.05). OCD patients with increased ALFF in the left superior frontal gyrus and right middle frontal gyrus, along with decreased ALFF in the left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and reduced FC between the left middle frontal gyrus-right angular gyrus, had a higher likelihood of SP (log OR (95% CI)=8.5(4.0-14.2), 8.0(1.7-16.4), -8.9(-15.2--4.4), -5.2 (-9.1--2.3), -4.1(-6.9--1.7), -7.0(-13.2--1.8); all P<0.05). Conclusion:Altered functional activity in the left superior frontal gyrus, right middle frontal gyrus, left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and abnormal FC between the left middle frontal gyrus and right angular gyrus represent key neuroimaging features of OCD patients with SP.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

Background:Colorectal cancer is a common malignant tumor in the digestive tract.The existing treatment methods and drugs have disadvantages such as significant toxicity and side effects,so there is an urgent need to develop new drugs with high efficiency and low toxicity.Aims:To investigate the potential mechanism of Nodosin in inducing apoptosis of colorectal cancer cells.Methods:Colorectal cancer cell lines SW480 and HCT116 were cultured with 0,5,10 and 20 μmol/L Nodosin for 24 hours,or cultured with 10 μmol/L Nodosin for 0,12,24 and 48 hours.The cell viability was measured by CCK-8 assay,and the protein expressions of PARP1,mTOR,p-mTOR and LC3BⅡ were detected by Western blotting.After pretreated with the autophagy inhibitor 3-methyladenine(3-MA)5 mmol/L for 4 hours,SW480 and HCT116 cells were cultured with 10 μmol/L Nodosin for 24 hours.The protein expressions of PARP1 and LC3BⅡ were detected by Western blotting.Results:Nodosin could decrease the cell viability of SW480 and HCT116 cells in a dose-and time-dependent manner,increase the expressions of apoptosis-related protein cleaved PARP1 and autophagy-related protein LC3BⅡ,and inhibit the protein expression of p-mTOR.Pretreatment of the autophagy inhibitor 3-MA could inhibit the expressions of apoptosis-related protein cleaved PARP1 and autophagy-related protein LC3BⅡ induced by Nodosin.Conclusions:Nodosin can induce apoptosis of colorectal cancer cells by inhibiting mTOR pathway and activating autophagy.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.