ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective Amyotrophic lateral sclerosis(ALS)is a progressive and fatal neurodegenerative disease.Mutations in the Cu/Zn superoxide dismutase 1 gene(SOD1)have been identified as the cause of familial ALS.Sequencing the SOD1 gene may be helpful for patients with a suspected family history of ALS.This article reports for the first time a case of amyotrophic lateral sclerosis with SOD1-p.A5S mutation in Han Chinese and summarizes its clinical characteristics.Method and Results This is the first report on Chinese Han of ALS with SOD1-p.A5S mutation and review of relevant case literature to summarize its clinical characteristics.The study case is a 34-year-old male who was admitted to the Neurology Department of The First Affiliated Hospital of Xi'an Jiaotong University with a complaint of"weakness in both lower limbs for 2 years,worsening with both hands for 6 months".The main clinical manifestations were progressive limb weakness,no swallowing difficulties or cognitive impairment.Further improvement of routine examinations and electromyography after admission were made to rule out other diagnoses,and genetic testing was conducted.Based on the patient's typical clinical manifestations and evidence of involvement of lower motor neurons in the cervical,thoracic,and lumbar spinal cord areas indicated by electromyography,other diagnoses and characteristic gene testing results were reasonably excluded,and ALS was diagnosed.The genetic testing results indicated that the patient had a heterozygous mutation in SOD1 exon 1,c.13G＞T(p.A5S),and his mother had a suspicious medical history but died without genetic verification.After discharge,the follow-up period lasted until August 21,2022,with a total of 38 months and a course of 62 months.Further review of the clinical characteristics of other patients with the same site mutation reported in the literature reveals that the progress of this patient with the mutation was slower than that of other patients with the same site mutation reported in the literature.Conclusion This study shows that gene sequencing is a powerful tool for diagnosing familial ALS.The mutation of c.13G＞T(p.A5S)in exon 1 of SOD1 is a rare pathogenic variation.The progress of patients with this subtype is slow,which further indicates that gene detection has important value in the diagnosis and prognosis of ALS.

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Background/Aims: In patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), the optimal timing of endoscopy is still a matter of dispute. We conducted a systematic review and meta-analysis to determine the clinical benefit of early endoscopy. Methods: A literature search of the MEDLINE, Embase, and Cochrane databases was conducted to identify publications from inception to March 1, 2022. Eligible studies included observational cohort studies and randomized controlled trials that reported clinical outcomes of endoscopy in patients with ANVUGIB. ANVUGIB patients who underwent endoscopy within 24 hours of admission were considered to have had an early endoscopy. The primary outcome was the mortality rate in ANVUGIB patients who had early or nonearly endoscopy. Results: The final analysis included five randomized controlled studies (RCTs) and 20 observational studies from the 1,206 identified articles. The mortality rate was not significantly reduced among patients who received endoscopy performed within 24 hours, whether in cohort studies nor in RCTs. For subgroup analysis, a higher mortality rate was found only among patients who received very early endoscopy within 12 hours (odds ratio, 1.66; p<0.001, I 2 =0) in cohort studies. No significant difference in mortality rates was found among patients at high risk of bleeding who received early versus nonearly endoscopy. Conclusions Early endoscopy within 24 hours does not appear to significantly reduce the mortality rates of patients with ANVUGIB. Further well-designed studies are warranted to address if very early endoscopy within 12 hours can provide a clinical benefit for patients at high risk of bleeding.

Objective:To explore the value of conventional ultrasonography combined with cervical compression in the diagnosis of orbital venous malformation (OVM).Methods:A total of 43 patients with suspected OVM were admitted in sequentially from January 2019 to July 2022 in the Third Medical Center of PLA General Hospital. All patients were examined by ultrasonography combined with cervical compression and demonstrated by operation or digital subtraction angiography (DSA). The conventional ultrasound features of OVM were summarized, and the value of conventional ultrasonography combined with cervical compression in the diagnosis of OVM was discussed.Results:The features of the conventional ultrasound combined with cervical compression for diagnosis of OVM were as follows: the interior of lesion was mainly tubular structure, and the compression test was positive. After cervical compression, the lesion enlarged and the inner diameter of the internal tubular structure widened. Doppler flow imaging showed that the interior of lesion was mainly venous blood flow. Compared with the results of postoperative pathology or DSA, the sensitivity, specificity, accuracy and positive predictive value of ultrasonography combined with cervical compression were 0.952, 1.000, 95.3% and 100%, respectively. The results of Fisher exact diagnosis showed that there was no significant difference between ultrasonography and operation or DSA of OVM( P>0.05). Conclusions:Conventional ultrasound combined with cervical compression can be used as an effective method for the diagnosis of OVM.

【Objective】 To explore the factors affecting Babinski sign in amyotrophic lateral sclerosis (ALS). 【Methods】 We enrolled 262 patients diagnosed with ALS with adequate data in Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University from 2015 to 2020. The relationship between the clinical characteristics of patients with positive and negative Babinski sign was analyzed for both sides, respectively. Furthermore, for patients with left or right lower limb weakness complaint, the relationship between Babinski sign and the lower limb involvement characteristics was analyzed. 【Results】 Positive Babinski sign was positively correlated with higher diagnostic category (left correlation coefficient 0.297, P<0.001; right correlation coefficient 0.292, P<0.001). Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score was lower in patients with positive Babinski sign (left P=0.001, right P=0.001); the proportion of complaints of ipsilateral lower limb weakness was higher (left P=0.008, right P=0.038); the positive rate of ipsilateral upper limb Hoffmann sign was higher (left P=0.004, right P=0.002). In patients with complaints of lower limb weakness, positive Babinski sign was positively correlated with better foot dorsiflexor muscle strength (left correlation coefficient 0.207, P=0.021; right correlation coefficient 0.264, P=0.003), and the proportion of ipsilateral tibialis anterior atrophy was lower in positive Babinski sign group (left P<0.001, right P=0.008); the ratio of ipsilateral common peroneal nerve compound muscle action potential (CMAP)/tibial nerve CMAP was different in positive Babinski sign and negative groups (left P=0.008, right P=0.015), which were positively correlated (left correlation coefficient 0.246, P=0.007; right correlation coefficient 0.223, P=0.015). 【Conclusion】 Patients with positive Babinski sign usually have a higher diagnostic category and more extensive clinical involvement. In ALS patients with complaints of lower limb weakness, Babinski sign is more likely to be elicited when the degree of weakness and atrophy of the anterior calf muscles is relatively low.

【Objective】 To investigate cortical thickness changes in the face-head region of the primary motor cortex (PMC) and its effect on survival in amyotrophy lateral sclerosis (ALS) patients. 【Methods】 A retrospective analysis was performed on 105 ALS patients who underwent head MRI scan at the same time. The A4hf (face-head) region of PMC was used as the region of interest (ROI). According to clinical symptoms, patients were divided into two groups: bulbar involvement and non-bulbar involvement. The differences of clinical features and cortical thickness in ROI were analyzed. According to the symptoms of bulbar palsy, physical examination of nervous system and EMG of tongue muscle, the patients with bulbar palsy were divided into lower motor neuron (LMN), upper motor neuron (UMN) and LMN+UMN groups. The differences of bulbar subgroup score and ROI of cortical thickness were analyzed. Age at onset, body mass index, delayed time of diagnosis, bulbar subgroup score, and ROI cortical thickness were included in survival analysis. 【Results】 ① The ROI cortical thickness was significantly lower in bulbar involvement group than non-bulbar involvement group (-0.198±0.87 vs. 0.235±0.95, P=0.017). ② There were no significant differences in the bulbar subgroup scores or cortical thickness of ROI between LMN, UMN and LMN+UMN groups (P>0.05). ③ Survival analysis showed age of onset (HR=3.296, 95% CI:1.63-6.664, P=0.001), delayed time of diagnosis (HR=0.361, 95% CI:0.184-0.705, P=0.003), bulbar subgroup score (HR 0.389, 95% CI:0.174-0.868, P=0.021), and ZRE_ROI cortical thickness (HR=2.309, 95% CI:1.046-5.096, P=0.038) were independent influencing factors of ALS survival. 【Conclusion】 Cortical thickness in A4hf (face-head) region can more objectively reflect UMN signs of region bulbar. In addition to age of onset and delayed time of diagnosis, bulbar subgroup score and cortical thickness of face-head region are also independent influencing factors, and cortical thinning in face-head region is a protective factor for survival of ALS patients.

【Objective】 The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to determine objective and sensitive UMN degeneration markers for an accurate and early diagnosis. 【Methods】 A total of 108 ALS patients and 90 age- and gender-matched control subjects were recruited from ALS Clinic of The First Affiliated Hospital of Xi’an Jiaotong University. The motor homunculus cortex thickness data in MRI were collected from all the participants. The clinical characteristics and UMN clinical examination of bulbar, cervical, thoracic and lumbosacral regions were collected from the ALS patients. 【Results】 Cortical thickness was significantly thinner in the ALS group than in the control group in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the global UMN positive group was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). The cortical thickness of the UMN positive group in the corresponding region was significantly thinner than that of control groups in bilateral head-face-bulbar and upper-limb areas (P<0.05). 【Conclusion】 The thinning of the motor homunculus cortex can be used as an objective marker of UMN involvement in ALS patients in clinical practice.

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans ; Mice ; Animals ; Cell Line, Tumor ; Nitric Oxide Donors/pharmacology* ; Sesquiterpenes/pharmacology* ; Leukemia/drug therapy* ; Biological Assay ; Cell Proliferation

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb₁ were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb₁ was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg^-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg^-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb₁ at 24 h were 16.41， 4.23， 4.15 μg∙cm^-2∙h^-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm^-2∙h^-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb₁ was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.