Pharmacokinetics and bioequivalence study of two ciprofloxacin hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions: A randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover study.

OBJECTIVE: The study mainly aimed to determine the bioequivalence of two branded ciprofloxacin hydrochloride tablets (250 mg) under fasting and fed conditions. MATERIALS AND METHODS: The study was carried out in 48 healthy Chinese subjects under fasting and fed conditions with a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design. In each period of the study, the subjects were assigned to receive a single oral dose of 250 mg ciprofloxacin hydrochloride. Blood samples were collected from 1 hour before dosing to 36 hours after administration with 16 timepoints in total. The bioequivalence analysis was performed after ln-transformation of the ciprofloxacin pharmacokinetic parameters including Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 48 subjects were enrolled in the fasting and fed studies, and 1 of the subjects was excluded before drug administration. In the fasting study, the 90% CIs for the test/reference geometric mean ratios (GMRs) of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 85.41 - 100.97%, 95.40 - 100.27%, and 95.48 - 100.30%, respectively. For the fed study, the 90% CIs for the test/reference GMRs of the ln-transformed data for Cmax, AUC0-t, and AUC0-∞ were 90.15 - 113.75%, 99.10 - 103.77%, and 99.11 - 103.80%, respectively. These values all fell within the standard acceptance range of 80 - 125%. CONCLUSION: In the study, the generic (test) product of ciprofloxacin hydrochloride 250 mg was bioequivalent to the innovator (reference) product after single-, oral-dose administration under fasting and fed conditions.

Cue-dependent safety and fear learning in a discriminative auditory fear conditioning paradigm in the mouse.

Discrimination between sensory stimuli associated with safety and threat is crucial for behavioral decisions. Discriminative conditioning paradigms with two acoustic conditioned stimuli (one paired with shock [CS+], the other unpaired with shock [CS-]) have been widely used as an experimental model for fear learning. However, no attention has been paid to the effect of the CS- on safety in the paradigms, because the CS- served as a neutral cue or elevated the freezing level due to fear generalization although less effectively than the CS+. By using a noise and a tone as two acoustic CSs in a discriminative auditory fear conditioning (AFC) paradigm, here we demonstrate that mice learn safety for the CS- while showing fear for the CS+ with opposing emotional behaviors. We found that after learning mice exhibited a significant suppression of context-dependent freezing during the CS-, but not during the CS+, indicating learned safety without fear generalization for the CS-. In contrast, the mice showed an enhanced level of freezing during the CS+ even in a novel spatial context, indicating cued fear for the CS+. Moreover, the CS+ also induced rapid defensive behaviors, whereas the CS- disinhibited normal exploratory behaviors. On the other hand, mice showed no significant suppression of contextual fear during the CS- in a paradigm with a pair of tone CSs at different frequencies, although they clearly discriminated the two tones. These results suggest our AFC paradigm with the noise and tone CSs as a useful experimental model for cue-dependent discriminative learning of safety and threat.

Regulation of membrane KCNQ1/KCNE1 channel density by sphingomyelin synthase 1.

Sphingomyelin synthase (SMS) catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. We previously showed that SMS1 deficiency leads to a reduction in expression of the K(+) channel KCNQ1 in the inner ear (Lu MH, Takemoto M, Watanabe K, Luo H, Nishimura M, Yano M, Tomimoto H, Okazaki T, Oike Y, and Song WJ. J Physiol 590: 4029-4044, 2012), causing hearing loss. However, it remains unknown whether this change in expression is attributable to a cellular process or a systemic effect in the knockout animal. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1 currents in individual cells. To this end, we expressed the KCNQ1/KCNE1 channel in human embryonic kidney 293T cells and evaluated the effect of SMS1 manipulations on the channel using whole cell recording. Application of tricyclodecan-9-yl-xanthogenate, a nonspecific inhibitor of SMSs, significantly reduced current density and altered channel voltage dependence. Knockdown of SMS1 by a short hairpin RNA, however, reduced current density alone. Consistent with this, overexpression of SMS1 increased the current density without changing channel properties. Furthermore, application of protein kinase D inhibitors also suppressed current density without changing channel properties; this effect was nonadditive with that of SMS1 short hairpin RNA. These results suggest that SMS1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner.

Greenwood frequency-position relationship in the primary auditory cortex in guinea pigs.

Although orderly representation of sound frequency over space is a hallmark feature of the primary auditory cortex (A1), the quantitative relationship between sound frequency and cortical position is unclear. We examined this relationship in the guinea pig A1 by presenting a series of stimulus tones with a wide frequency range, and recording the evoked cortical responses using an optical imaging technique with high spatial resolution. We identified the cortical positions of three best-frequency indices for each tone: the onset response position, the peak amplitude position, and the maximum rise rate position of the response. We found a nonlinear log frequency-position relationship for each of the three indices, and the frequency-position relationship was always well described by a Greenwood equation, with correlation coefficients greater than 0.98. The cortical magnification factor, measured in octave/mm, was found to be a function of frequency, i.e. not a constant. Our results are novel in that they demonstrate a quantitative relationship between sound frequency and cortical position in the guinea pig A1, as described by the Greenwood equation.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.

Neurochemical properties for defining subdivisions of the mouse medial geniculate body.

The medial geniculate body (MGB) exhibits anatomical and physiological properties that underlie its role in the auditory system. Anatomical properties, including myelo- and cyto-architecture, are used to identify MGB subdivisions. Recently, neurochemical properties, including calcium-binding proteins, have also been employed to define the MGB subdivisions. Because these properties do not show clear boundaries in the MGB and do not involve anatomical connectivity, whether the MGB subdivisions can be defined based on anatomical and neurochemical properties remains unclear. In this study, 11 different neurochemical markers were employed for defining the MGB subdivisions. In terms of anatomical connectivity, immunoreactivities for vesicular transporter demonstrated glutamatergic, GABAergic and glycinergic afferents and provided clues about the boundaries of the MGB subdivisions. On the other hand, the distribution of novel neurochemical markers of the MGB demonstrated distinct boundaries of the MGB subdivisions and resulted in the discovery of a putative homolog of the rabbit internal division of the MGB. Additionally, corticotropin-releasing factor was expressed in the larger neurons in the medial division of the MGB (MGm), particularly in the caudal MGm. Lastly, the analysis of anatomical details by measuring the size and density of vesicular transporters revealed heterogeneity among the MGB subdivisions. Our results demonstrate that the MGB is composed of five subdivisions based on their anatomical and neurochemical properties.

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive drinking behavior.

The insular cortex (insula) is known to play a modulatory role in feeding and drinking. Previous studies have revealed anterior-posterior differences of subcortical projections and roles for the insula, yet the anatomical and functional heterogeneity among the cortical layers remains poorly understood. Here, we show that layer 5 of the mouse dysgranular insula has two distinct neuronal subpopulations along the entire anterior-posterior axis: The L5a population, expressing NECAB1, projects bilaterally to the lateral and capsular divisions of the central amygdala, and the L5b population, expressing CTIP2, projects ipsilaterally to the parasubthalamic nucleus and the medial division of the central amygdala. Optogenetically activating L5a and L5b neuronal populations in thirsty male mice led to suppressed and facilitated water spout licking, respectively, without avoidance against or preference for the spout paired with the opto-stimulation. Our results suggest sublayer-specific bidirectional modulatory roles of insula layer 5 in the motivational aspect of appetitive behavior.

Temporal profiles of neuronal responses to repeated tone stimuli in the mouse primary auditory cortex.

How the auditory system processes temporal information of sound has been investigated extensively using repeated stimuli. Recent studies on how the response of neurons in the primary auditory cortex (A1) changes with the progression of stimulus repetition, have reported response temporal profiles of two categories: "adaptation", i.e., gradual decrease, and "facilitation", i.e., gradual increase. To explore the existence of profiles of other categories and to examine the tone-frequency-dependence of the profile category in single neurons, here we studied the response of mouse A1 neurons to four or five tone-trains; each train comprised 10 identical tone pips, with 0.5-s inter-tone-intervals, and the four or five trains differed only in tone frequency. The response to each tone in a train was evaluated using the peak of the ON response, and how the peak response changed with the tone number in the train, i.e., the response temporal profile, was examined. We confirmed the existence of profiles of both "adaptation" and "facilitation" categories; "adaptation" could be further subcategorized into "slow adaptation" and "fast adaptation" profiles, with the latter being encountered more frequently. Moreover, two new categories of non-monotonic profiles were identified: an "adaptation with recovery" profile and a "facilitation followed by adaptation" profile. Examination of single neurons with trains of different tone frequencies revealed that some A1 neurons exhibited profiles of the same category to tone trains of different tone frequencies, whereas others exhibited profiles of different categories, depending on the tone frequency. These results demonstrate the variety in the response temporal profiles of mouse A1 neurons, which may benefit the encoding of individual tones in a train.

[Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty].

OBJECTIVE: To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty. METHODS: A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed. RESULTS: A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7). CONCLUSION: Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

Deficiency of sphingomyelin synthase-1 but not sphingomyelin synthase-2 causes hearing impairments in mice.

Sphingomyelin (SM) is a sphingolipid reported to function as a structural component of plasma membranes and to participate in signal transduction. The role of SM metabolism in the process of hearing remains controversial. Here, we examined the role of SM synthase (SMS), which is subcategorized into the family members SMS1 and SMS2, in auditory function. Measurements of auditory brainstem response (ABR) revealed hearing impairment in SMS1−/− mice in a low frequency range (4­16 kHz). As a possible mechanism of this impairment, we found that the stria vascularis (SV) in these mice exhibited atrophy and disorganized marginal cells. Consequently, SMS1−/− mice exhibited significantly smaller endocochlear potentials (EPs). As a possible mechanism for EP reduction, we found altered expression patterns and a reduced level of KCNQ1 channel protein in the SV of SMS1−/− mice. These mice also exhibited reduced levels of distortion product otoacoustic emissions. Quantitative comparison of the SV atrophy, KCNQ1 expression, and outer hair cell density at the cochlear apical and basal turns revealed no location dependence, but more macrophage invasion into the SV was observed in the apical region than the basal region, suggesting a role of cochlear location-dependent oxidative stress in producing the frequency dependence of hearing loss in SMS1−/− mice. Elevated ABR thresholds, decreased EPs, and abnormal KCNQ1 expression patterns in SMS1−/− mice were all found to be progressive with age. Mice lacking SMS2, however, exhibited neither detectable hearing loss nor changes in their EPs. Taken together, our results suggest that hearing impairments occur in SMS1−/− but not SMS2−/− mice. Defects in the SV with subsequent reductions in EPs together with hair cell dysfunction may account, at least partially, for hearing impairments in SMS1−/− mice.

Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice.

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic ß-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic ß-cells.

Region-dependent Millisecond Time-scale Sensitivity in Spectrotemporal Integrations in Guinea Pig Primary Auditory Cortex.

Spectrotemporal integration is a key function of our auditory system for discriminating spectrotemporally complex sounds, such as words. Response latency in the auditory cortex is known to change with the millisecond time-scale depending on acoustic parameters, such as sound frequency and intensity. The functional significance of the millisecond-range latency difference in the integration remains unclear. Actually, whether the auditory cortex has a sensitivity to the millisecond-range difference has not been systematically examined. Herein, we examined the sensitivity in the primary auditory cortex (A1) using voltage-sensitive dye imaging techniques in guinea pigs. Bandpass noise bursts in two different bands (band-noises), centered at 1 and 16 kHz, respectively, were used for the examination. Onset times of individual band-noises (spectral onset-times) were varied to virtually cancel or magnify the latency difference observed with the band-noises. Conventionally defined nonlinear effects in integration were analyzed at A1 with varying sound intensities (or response latencies) and/or spectral onset-times of the two band-noises. The nonlinear effect measured in the high-frequency region of the A1 linearly changed depending on the millisecond difference of the response onset-times, which were estimated from the spatially-local response latencies and spectral onset-times. In contrast, the low-frequency region of the A1 had no significant sensitivity to the millisecond difference. The millisecond-range latency difference may have functional significance in the spectrotemporal integration with the millisecond time-scale sensitivity at the high-frequency region of A1 but not at the low-frequency region.

[Clinical effects of arthroscopy-assisted anterior cruciate ligament tibial eminence avulsion fracture compared with traditional open surgery:a Meta-analysis].

OBJECTIVE: To systematically evaluate the clinical efficacy of arthroscopy and traditional incision in the treatment of tibial avulsion fracture of anterior cruciate ligament (ACL). METHODS: From July 2010 to July 2020, clinical comparative trial about arthroscopy and traditional incision in the treatment of ACL tibial avulsion fracture was conducted by using computer-based databases, including Embase, Pubmed, Central, Cinahl, PQDT, CNKI, Weipu, Wanfang, Cochrane Library, CBM. Literature screening and data extraction were carried out according to the inclusion and exclusion criteria, and the quality of the included literature was evaluated by improved Jadad score and Ottawa Newcastle scale (NOS). The operation time, hospital stay, fracture healing time, knee range of motion, postoperative excellent and good rate, complication rate, Lysholm score, International Knee Documentation Committee (IKDC) score and Tegner score were statistically analyzed by Review Manager 5.3 software. RESULTS: Finally, 16 literatures were included, including 1 randomized controlled trial and 15 non randomized controlled trials, with a total of 822 patients (405 in arthroscopy group and 417 in traditional incision group). Meta analysis showed that the operation time [MD=-9.03, 95% CI(-14.36, -3.70), P<0.001], hospital stay [MD=-5.81, 95%CI(-9.32, -2.31), P=0.001] and fracture healing time [MD=-14.61, 95% CI(-17.93, -11.28), P<0.001] in the arthroscopy group were better than those in the traditional incision group. The incidence of complications in arthroscopy group was lower than that in traditional incision group[OR=0.15, 95%CI(0.07, 0.33), P<0.001]. The postoperative excellent and good rate[OR=4.39, 95%CI (1.96, 9.82), P<0.001], knee mobility[MD=6.78, 95%CI(2.79, 10.77), P<0.001], Lysholm score[MD=11.63, 95%CI(4.91, 18.36), P<0.001], IKDC score[MD=7.83, 95%CI(6.09, 9.57), P<0.001] and Tegner score[MD=0.60, 95%CI(0.31, 0.89), P<0.001] in the arthroscopic group were higher than those in the traditional incision group. CONCLUSION: Compared with the traditional open reduction and internal fixation, arthroscopic surgery in patients with ACL tibial avulsion fracture can shorten the operation time, hospital stay and fracture healing time, reduce the incidence of postoperative complications, and obtain good postoperative knee function. It can be recommended as one of the first choice for patients with ACL tibial avulsion fracture.

Pharmacokinetics and Bioequivalence of Two Formulations of Rosuvastatin Following Single-dose Administration in Healthy Chinese Subjects Under Fasted and Fed Conditions.

The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7 days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10 mg. Blood samples were collected from pre-dose to 72 hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including Cmax , AUC0-t , and AUC0-∞ . In the present study, 95% confidence intervals (CIs) of test/reference geometric mean ratios (GMRs) of Cmax , AUC0-t , and AUC0-∞ under the fasted and fed conditions were all within the acceptance range of 80%-125%. Additionally, only one subject experienced one adverse event (AE). High-fat meals reduced the Cmax , AUC0-t , and AUC0-∞ , but had no significant effects on the λz, t1/2 , or Tmax of rosuvastatin. In the current study, the test product was bioequivalent to the reference product, and a single dose of rosuvastatin (10 mg) was well-tolerated. Food decreased the systemic exposure of rosuvastatin without the effects on the Tmax or elimination rate.

Identification and characterization of an insular auditory field in mice.

We used voltage-sensitive-dye-based imaging techniques to identify and characterize the insular auditory field (IAF) in mice. Previous research has identified five auditory fields in the mouse auditory cortex, including the primary field and the anterior auditory field. This study confirmed the existence of the primary field and anterior auditory field by examining the tonotopy in each field. Further, we identified a previously unreported IAF located rostral to known auditory fields. Pure tone evoked responses in the IAF exhibited the shortest latency among all auditory fields at lower frequencies. A rostroventral to dorsocaudal frequency gradient was consistently observed in the IAF in all animals examined. Neither the response amplitude nor the response duration changed with frequency in the IAF, but the area of activation exhibited a significant increase with decreasing tone frequency. Taken together, the current results indicate the existence of an IAF in mice, with characteristics suggesting a role in the rapid detection of lower frequency components of incoming sound.

Voltage-gated K+ channel KCNQ1 regulates insulin secretion in MIN6 ß-cell line.

KCNQ1, located on 11p15.5, encodes a voltage-gated K(+) channel with six transmembrane regions, and loss-of-function mutations in the KCNQ1 gene cause hereditary long QT syndrome. Recent genetic studies have identified that single nucleotide polymorphisms located in intron 15 of the KCNQ1 gene are strongly associated with type 2 diabetes and impaired insulin secretion. In order to understand the role of KCNQ1 in insulin secretion, we introduced KCNQ1 into the MIN6 mouse ß-cell line using a retrovirus-mediated gene transfer system. In KCNQ1 transferred MIN6 cells, both the density of the KCNQ1 current and the density of the total K(+) current were significantly increased. In addition, insulin secretion by glucose, pyruvate, or tolbutamide was significantly impaired by KCNQ1-overexpressing MIN6 cells. These results suggest that increased KCNQ1 protein expression limits insulin secretion from pancreatic ß-cells by regulating the potassium channel current.

Differentiation-inducing activity of hydroxycamptothecin on cancer stem-like cells derived from hepatocellular carcinoma.

BACKGROUND: Hydroxycamptothecin (HCPT) is an anti-tumor agent that can induce differentiation in human cancer cells. Recent evidence indicates that side population (SP) cells possess characteristics of stem-like cells, and may be capable of initiating tumor growth. AIMS: The present study investigated the differentiation of cancer stem-like cells derived from hepatocellular carcinoma. METHODS AND RESULTS: Flow cytometry was used to isolated SP cells from HCC cell line (MHCC97 cells). These SP cells exhibit several stem-like cell characteristics that are distinct from the main population (MP) cells in vitro. After 3 days of induction with a low concentration of HCPT, the SP cells lost their capacity to proliferate and invade, and their tumorigenicity declined. Based on real-time quantitative RT-PCR, we also found that the expression of hepatocyte-specific markers such as α-fetoprotein, albumin, hepatocyte nuclear factor-4 and miR-122 gradually changed during the differentiation of SP cells. CONCLUSIONS: Our data suggest that a low concentration of HCPT can induce hepatocyte-specific differentiation of cancer stem-like cells from MHCC97 cells, offering a possible therapeutic strategy for the treatment of human malignancies.

The methods of reconstruction of pancreatic digestive continuity after pancreaticoduodenectomy: a meta-analysis of randomized controlled trials.

BACKGROUND: Pancreatic fistula (PF) is an important factor responsible for the considerable morbidity associated with pancreaticoduodenectomy (PD). There have been many techniques proposed for the reconstruction of pancreatic digestive continuity to prevent fistula formation but which is best is still highly debated. We carried out a systematic review and meta-analysis to determine the effectiveness of methods of anastomosis after PD. METHODS: A full literature search was conducted in the Cochrane Controlled Trials Register Databases, Medline, and other resources irrespective of language. Randomized controlled trials (RCTs) were considered for inclusion. Analyses were carried out using RevMan software. RESULTS: In all, ten RCTs that included a total of 1,408 patients were included. The meta-analysis showed that the PF, postoperative complications, biliary fistula, mortality, reoperation, and length of hospital stay were not statistically different between the pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) groups. The PF, postoperative complications, mortality, and reoperation were not statistically different between the duct-to-mucosa PJ and PJ groups. Binding PJ significantly decreased the PF and postoperative complications compared with conventional PJ. The PF, postoperative complications, and mortality were not statistically different between ligation of the pancreatic duct without anastomosis versus PJ. CONCLUSION: No pancreatic reconstruction technique after PD was found to be applicable to all kinds of pancreatic remnants in our systematic review and meta-analysis. Some new approaches such as binding PJ and modified PG will be considered for study in the future.

Postnatal development of subfields in the core region of the mouse auditory cortex.

The core region of the rodent auditory cortex has two subfields: the primary auditory area (A1) and the anterior auditory field (AAF). Although the postnatal development of A1 has been studied in several mammalian species, few studies have been conducted on the postnatal development of AAF. Using a voltage-sensitive-dye-based imaging method, we examined and compared the postnatal development of AAF and A1 in mice from postnatal day 11 (P11) to P40. We focused on the postnatal development of tonotopy, the relative position between A1 and AAF, and the properties of tone-evoked responses in the subfields. Tone-evoked responses in the mouse auditory cortex were first observed at P12, and tonotopy was found in both A1 and AAF at this age. Quantification of tonotopy using the cortical magnification factor (CMF; octave difference per unit cortical distance) revealed a rapid change from P12 to P14 in both A1 and AAF, and a stable level from P14. A similar time course of postnatal development was found for the distance between the 4 kHz site in A1 and AAF, the distance between the 16 kHz site in A1 and AAF, and the angle between the frequency axis of A1 and AAF. The maximum amplitude and rise time of tone-evoked signals in both A1 and AAF showed no significant change from P12 to P40, but the latency of the responses to both the 4 kHz and 16 kHz tones decreased during this period, with a more rapid decrease in the latency to 16 kHz tones in both subfields. The duration of responses evoked by 4 kHz tones in both A1 and AAF showed no significant postnatal change, but the duration of responses to 16 kHz tones decreased exponentially in both subfields. The cortical area activated by 4 kHz tones in AAF was always larger than that in A1 at all ages (P12-P40). Our results demonstrated that A1 and AAF developed in parallel postnatally, showing a rapid maturation of tonotopy, slow maturation of response latency and response duration, and a dorsal-to-ventral order (high-frequency site to low-frequency site) of functional maturation.

Studies of Articular Cartilage Repair from 2009 to 2018: A Bibliometric Analysis of Articles.

OBJECTIVE: To perform a bibliometric analysis of research on articular cartilage repair published in Chinese and English over the past decade. Fundamental and clinical research topics of high interest were further comparatively analyzed. METHODS: Relevant studies published from 1 January 2009 to 31 December 2018 (10 years) were retrieved from the Wanfang database (Chinese articles) and six databases, including MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the website "Web of Science" (English articles), using key words: "articular cartilage" AND "injury" AND "repair". The articles were categorized according to research focuses for a comparative analysis between those published in Chinese vs English, and further grouped according to publication date (before and after 2014). A comparative analysis was performed on research focus to characterize the variation in research trends between two 5-year time spans. Moreover, articles were classified as basic and clinical research studies. RESULTS: Overall, 5762 articles were retrieved, including 2748 in domestic Chinese journals and 3014 in international English journals. A total of 4937 articles focused on the top 10 research topics, with the top 3 being stem cells (32.1%), tissue-engineered scaffold (22.8%), and molecular mechanisms (16.4%). Differences between the numbers of Chinese and English papers were observed for 3 topics: chondrocyte implantation (104 vs 316), osteochondral allograft (27 vs 86), and microfracture (127 vs 293). The following topics gained more research interest in the second 5-year time span compared with the first: microfracture, osteochondral allograft, osteochondral autograft, stem cells, and tissue-engineered scaffold. Articles with a focus on three-dimensional-printing technology have shown the fastest increase in publication numbers. Among 5613 research articles, basic research studies accounted for the majority (4429), with clinical studies described in only 1184 articles. The top 7 research topics of clinical studies were: chondrocyte implantation (28.7%), stem cells (21.9%), microfracture (19.2%), tissue scaffold (10.6%), osteochondral autograft (10.5%), osteochondral allograft (6.3%), and periosteal transplantation (2.8%). CONCLUSION: Studies focused on stem cells and tissue-engineered scaffolds led the field of damaged articular cartilage repair. International researchers studied allograft-related implantation approaches more often than Chinese researchers. Traditional surgical techniques, such as microfracture and osteochondral transplantation, gained high research interest over the past decade.